Researchreport2006

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THE UNIVERSITY OF SYDNEY School of Chemistry 2006 Research Report Message from the Head of School Page 3 Advice to Postgraduate Candidates Page 4 New Faces for 2006 Page 5 Research Reports Page 11 Research Centres Page 99 Research Facilities Page 107 Research Publications Page 111 Research Fellowships and Grants Page 131 Awards, Scholarships & Prizes Page 147 2006 Staff and Student Page 151 2006 Chemistry Graduates Page 161  School of Chemistry  Annual Research Report Professor Gregory G Warr Names in parentheses following research project titles refer to joint researchers. Those names with an asterisk or other symbols refer to non-University of Sydney Chemistry researchers. Head of School Telephone: +61 2 9351 2106 Facsimile: +61 2 9351 3329 Email: [email protected] School of Chemistry Building F11 Eastern Avenue The University of Sydney NSW 2006 AUSTRALIA Telephone: +61 2 9351 4504 Facsimile: +61 2 9351 3329 Email: [email protected]* Website: http://www.chem.usyd.edu.au/ *All staff can be emailed using:- [email protected] © Copyright School of Chemistry 2007 Cover Design and Editing by Ms Anne Woods School of Chemistry The University of Sydney Front Cover Top left: The illustration shows a conductive atomic force microscopy (AFM) tip on the top of a selfassembled monolayer of 1,8-octanedithiols (formed by PhD student Peter Cafe). This technique and the related scanning tunnelling microscopy (STM) technique is currently being used at the School of Chemistry to measure the single molecule conductance of various molecules for potential applications in molecular electronics. From the Head of School I n 2006 the School of Chemistry at the University of Sydney cemented its position as one of the top research Chemistry Departments in Australia. Members of the School enjoyed a 57% success rate in the ARC Discovery grants round announced in 2006 and were also awarded a number of very substantial Linkage grants. Staff and students of the School received a number of research awards during 2006 including the inaugural Alan Sargeson Award to Professor Cameron Kepert, the RACI’s Biota Award to Dr Kate Jolliffe, and Dr Deanna D’Alessandro who received the RACI Cornforth Medal for the most outstanding PhD thesis submitted in any branch of chemistry, chemical science or chemical technology. The School has about 33 research groups spanning a wide range of Chemistry disciplines with identified areas of research strength including: Biological and Medicinal Chemistry; Synthesis, Catalysis and Materials; Polymer and Colloid Chemistry; Computational and Theoretical Chemistry; Supramolecular Chemistry; Reaction Dynamics and Kinetics; and Chemical Spectroscopy. The School is well-equipped with modern research instrumentation including major research facilities for NMR Spectroscopy, Mass Spectrometry, X-ray Crystallography, Optical Spectroscopy, Electrochemistry, High Pressure Liquid Chromatography, Analytical and Preparative Gas Chromatography, and High Performance Computing. Research infrastructure (that underpins and supports all research programs) includes in-house mechanical and electronic workshops. The Madsen Library (as a branch of the main University Library) holds all of the main Chemistry titles and also provides on-line access to national and international databases. In 2006, staff at the University of Sydney held 43 ARC Discovery grants, 14 ARC Fellowships, 22 ARC Linkage grants and 1 Special Research Initiative Scheme grant. The School was award $16.8M in total research funding, including $13.7M from the Australian Research Council (ARC). In addition, $2.3M was obtained from other government sources and industry; $786,892 from University of Sydney grants, $589,359 from bequests, and $4,525 from other donations. Collaborative links with industry continued strongly through the Centre for Heavy Metals Research with Professor Peter Lay as Deputy Director, the Key Centre for Polymer Colloids with Professor Bob Gilbert as its Director and the Organic Synthesis Centre with Dr Malcolm McLeod as Director. All centres expanded already strong links with industry and other research organisations both locally and internationally. In 2006 there were approximately 104 graduate students enrolled in higher degrees in the School of Chemistry as well as 38 honours students undertaking a year of research to complete their undergraduate degree programs. This large cohort of research students fosters a strong and vibrant environment for research and this continues to be a real strength of the School. I would like to thank our Research Committee, chaired by Associate Professor Brendan Kennedy (Associate Head of School, Research), for managing research matters within the School. Top right: Illustration of a light-activated biosensor consisting of a ruthenium(II)terpyridine-cytochrome c bioconjugate (synthesised by PhD student Joshua R. Peterson) on a conductive surface with an conductive AFM tip on top. See Chem. Commun., 1899-1901, 2007. Bottom: STM image of a self-assembled monolayer of a platinum-metallomacrocycle (synthesised by MSc student Jonathon E. Beves). A model based on the X-ray structure of the this molecule is shown up top of the image. See Dalton Trans.,744-750, 2006. Professor Gregory G Warr Head of School  School of Chemistry Advice to Postgraduate Candidates The University of Sydney’s School of Chemistry is one of the largest chemistry departments in Australia with a strong record of achievement and an international research reputation. There are typically around 100 postgraduate students undertaking research towards doctorate and masters degrees. The School offers postgraduate programs in all areas of contemporary chemistry leading to the following degrees: i Master of Science (MSc) ii Doctor of Philosophy (PhD) iii Graduate Diploma in Science (equivalent to 4th year of a BSc degree) The School welcomes expressions of interest from both Australian and international students to undertake a postgraduate degree in Chemistry. All information on how to apply for candidature, scholarships, research projects in the School of Chemistry and other information for both Australian and international students may be found at: http://www.chem.usyd.edu.au/future/pg_degrees.htm If you do not have Web access, please contact: Australian Residents The Postgraduate Coordinator School of Chemistry, Building F11 Eastern Avenue The University of Sydney NSW 2006 AUSTRALIA Phone: +61 2 9351 4504 Facsimile: +61 2 9351 3329 Email: [email protected] Website: http://www.chem.usyd.edu.au/ International Students International Office Ground Floor, Building G12 (Services Building) 353 Abercrombie Street (Codrington Street entrance) The University of Sydney NSW 2006 AUSTRALIA Phone: +61 2 9351 4079 Facsimile: +61 2 9351 4013 Email: [email protected] Website: http://www.usyd.edu.au/international/ New Faces for 2006  School of Chemistry Associate Professor Michael Kassiou Brain and Mind Research Institute, Room 415 & School of Chemistry, Room 412c Telephone: +61 2 9351 0849 Facsimile: +61 2 9351 3329 Email: [email protected] http://www.chem.usyd.edu.au/about/staff_kassiou.html Medicinal Chemistry / Molecular Imaging Ligands for Imaging the Microglial Translator Protein (18 kDa) (James*, Luus*, Robertson) The recognition that microglia activation is closely linked to the pathophysiology of brain disease has made the Translator Protein (18 kDa) TSPO, formally known as the peripheral benzodiazepine receptor, an important therapeutic and diagnostic target. We investigated the structure activity profile of molecular probes based on pyrazolopyrimidines and determined parameters required for incorporation of radioisotopes while maintaining high binding affinity. The development of the first fluorinated pyrazolopyrimidine (DPA-714) has allowed us to establish the pharmacokinetics and pharmacodynamics of this new TSPO ligand when radiolabelled using in vivo imaging in living non-human primates. [18F]DPA-714: Baboon PET Imaging (Baboon Body – Papio hamadryas) 60 minutes p.i. Annual Research Report  a non-selective membrane pore which is permeable to hydrophilic molecules with molecular weight up to 900 Da. The physiological function of P2X7 is as yet unknown, however its high expression in immune cells, particularly microglia, and current research have suggested that it has an important role in neuroinflammatory and neurodegenerative processes. We have developed a series of polycyclic ligands which display potent antagonistic properties at the P2X7 receptor. Modification of the polycyclic moiety of these molecules represents new exciting approach for the development of suitable radiolabelled molecular probes for use in brain imaging of P2X7 receptors using positron emission tomography (PET). Sigma Receptors (Banister, Moussa, Coster*) Since the discovery of sigma receptors, research has been ongoing in an attempt to understand the functional roles of these sites. Initial interest in sigma receptors was largely motivated by the observation that the sigma site was a high affinity binding site for psychoactive drugs including many of the atypical antipsychotic drugs. Ligands which bind with high affinity at sigma receptors have been shown to modulate and interfere with several neurotransmitters and have potent activities in animal models suggestive of antipsychotic, cognitive enhancing, neuroprotective, and antidepressant activities. We have recently reported the synthesis and binding a novel series of trishomocubanes of the type 4-azahexacyclo[5.4.1.02,6.03,10.0 5,9.08,11]dodecane namely compounds 1 and 2 which display high affinity for sigma-2 and sigma-1 receptor subtypes respectively. These molecules have also been shown to modulate cocaine induced behaviours. These lead compounds provide the basis for further refinement of the binding and functional activity of this class. Arylalkyl 4-benzyl piperazines have only recently been reported as ligands for sigma receptors. This receptor is of interest since many psychoactive drugs including atypical antipsychotics bind to this site. We have developed the prototypic radioligand, 1-benzofuran-2-ylmethyl-4-(4-[11C]methoxybenzyl)piperazine, and evaluated its potential as a tracer in the living baboon brain (see images). We have demonstrated that this radioligand is capable of imaging in vivo sigma receptor density. This will allow correlations to be derived between changes in sigma receptor denisty and disease on-set and progression. Selected Publications [18F]DPA-714 (baseline) [18F]DPA-714 + DPA-714 (1 mg/kg) Evaluating Novel Neuroprotective Agents (Leaver*, Truong* Henderson*) Neuroprotective agents represent a novel therapeutic strategy towards the treatment of brain diseases. With the advent of high-resolution microPET technologies it has become possible to image animal models of neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease and Multiple Sclerosis. We are currently utilising models of such diseases for the evaluation of newly developed ligands targeting the Traslocator Protein (18 kDa), NR2B-NMDA and sigma receptor subtypes as potential neuroprotective agents. These models coupled with molecular imaging techniques allow for the in vivo evaluation of these pharmacological agents while ex vivo studies, using immunohistochemistry and neuropathological examination allow validation of imaging studies.  The Purinergic P2X7 Receptor (Gunosewoyo, Coster*, Bennett*) The P2X7 receptor is an unusual non-desensitising cation selective ion channel directly gated by extracellular ATP. This is the most interesting of the ionotropic P2X receptors. Upon stimulation by high concentrations of ATP it generates 1. Gunosewoyo, H, Coster, MJ and Kassiou, M. Molecular probes for P2X7 receptor studies. Curr. Med. Chem., 14, 1505-1523, 2007. 2. Boutin, H, Chauveau, F, Thominiaux, C, Kuhnast, B, Gregoire, MC, James, M, Jan, S, Brulon, V, Fontyn, Y, Selleri, S, Trebossen, R, Hantraye, P, Dolle, F, Tavitian, B and Kassiou, M. [11C]DPA-713:a novel peripheral benzodiazepine receptor PET ligand for in vivo imaging of neuroinflammation. J. Nucl. Med., 48, 573-581, 2007. 3. Quinlivan, M, Chalon, S, Vergote, J, Henderson, J, Katsifis, A, Kassiou, M and Guilloteau, D. Decreased vesicular acetylcholine transporter and α4β2 nicotinic receptor density in the rat brain following 192 IgG-saporin immunolesioning. Neurosci Lett., 415, 97-10, 2007. 4. Waterhouse, RN, Collier, TL and Kassiou, M. Imaging sigma receptors: Applications in drug development. Curr. Pharm. Design, 13, 51-72, 2007. 5. Kozikowski, AP, Chellappan, SK, Henderson, D, Fulton, R, Giboureau, N, Xiao, Y, Wei, ZL, Guilloteau, D, Emond, P, Dolle, F, Kellar, KJ and Kassiou, M. Novel acetylenic pyridines for use in PET imaging of nicotinic receptors. ChemMedChem., 2, 54-57, 2007. 6. Liu, X, Banister, SD, Christie, MJ, Banati, R, Meikle, S, Coster, MJ and Kassiou, M. Trishomocubanes: Novel sigma ligands modulate cocaine-induced behavioural effects. Eur J Pharmacol., 555, 37-42, 2007. 7. James, ML, Selleri, S and Kassiou M. Development of ligands for the peripheral benzodiazepine receptor. Curr. Med. Chem., 3, 1991-2001, 2006. 8. Truong, L, Allbutt, H, Kassiou, M and Henderson, JM. Developing a preclinical model of Parkinson’s disease: A study of behaviour in rats with graded 6-OHDA lesions. Behav. Brain Res., 169, 1-9, 2006. 9. Liu, X, Mattner, F, Katsifis, A, Christie, MJ and Kassiou, M. Influence of trishomocubanes on sigma receptor binding of N-(1benzyl-piperidin-4-yl)-4-[123I]iodobenzamide in vivo in the rat brain. Med. Chem., 1, 31-38, 2005. 10. Kassiou, M, Dannals, RF, Liu, X, Wong, DF, Ravert, RT and Scheffel, UA. Synthesis and in vivo evaluation of a new PET radioligand for studying sigma-2 receptors. Bioorg. Med. Chem., 13, 3623-3626, 2005. 11. James, ML, Fulton, RR, Henderson, DJ, Eberl, S, Meikle, SR, Thomson, S, Allan, RD, Dolle, F, Fulham, MJ and Kassiou M. Synthesis and in vivo evaluation of a novel peripheral benzodiazepine receptor PET radioligand. Bioorg. Med. Chem., 13, 6188-6194, 2005.  School of Chemistry Dr Peter Rutledge Annual Research Report  We are working to develop new iron-based oxidising systems which mirror these enzymatic reactions and convert simple hydrocarbons to oxidised products. Room 547 School of Chemistry, F11 Telephone: +61 2 9351 5020 Facsimile: +61 2 9351 3329 Email: [email protected] http://www.chem.usyd.edu.au/about/staff_rutledge.html Peptide-based Heavy Metal Sensors (Scully) Bio-Inspired synthesis and chemical biology Our research uses the tools of organic synthesis, bio-organic and bioinorganic chemistry to develop new biologically-inspired catalysts for important synthetic transformations and the breakdown of environmental contaminants. Heavy metals such as cadmium and mercury form some of the most toxic materials known, attacking their target organs at very low concentrations. Various industrial activities have caused levels of these heavy metals in the environment to rise over recent years. Some organisms have developed strategies to live in locales prone to high levels of cadmium and mercury pollution, using sulfur-rich proteins such as metallothioneins and phytochelatins to bind and sequester the toxic metal ions. These proteins incorporate a very high percentage of cysteine residues (≥ 30% of primary structure), making them effective agents for heavy metal sequestration. We are building on Nature’s approach to use thiol- and sulfide-rich peptides as agents for sensing and binding mercury and cadmium in the environment. By tethering these peptides to electrochemical reporters, we have developed a novel system for sensing these metals that is selective for mercury over cadmium and other thiophilic metals tested. Work is now underway to improve the sensitivity of these systems and to create novel agents for metal sequestration. Peptide Mimics of Nitrile Hydratase (Byrne, Houlihan) Cyanide and organic nitriles are well known chemical toxins, but such compounds also have considerable commercial utility and are used in a range of industrial processes. The strategies currently available to deal with the significant quantities of nitrile-containing waste generated through these processes are severely limited. Nitrile hydratase enzymes play central roles in the breakdown of nitriles in vivo, making them attractive targets for a bioremediation approach to the treatment of nitrile waste streams. Nitrile hydratases are also used increasingly as biocatalysts in the industrial synthesis of polymers and the asymmetric synthesis of fine chemicals incorporating amide functional groups. Crystal structures of nitrile hydratases from several organisms reveal a remarkable ligand environment 1 around the active site metal. Two nitrogen atoms from main-chain amides bind to the metal (cobalt(III) or iron(III)), along with three sulfur atoms, each in a different oxidation state. The five ligands are located in a short section of the protein’s primary sequence, spread across six amino acids in one peptide chain. We are developing new peptide and peptido-mimetic systems as bio-inspired catalysts for nitrile hydration, and as mechanistic probes to study the unusual sulfur oxidation that occurs at the active site and elucidate a detailed mechanism for nitrile hydratase catalysis. New Catalysts for Hydrocarbon Oxidation (Barry, Dungan, Wong) The conversion of simple hydrocarbons (alkanes, alkenes and aromatic compounds) to oxidised products (alcohols, epoxides and diols) is an important goal in synthetic organic chemistry. Nature uses a variety of iron-centred enzymes to oxidise such substrates cleanly and selectively. Non-heme iron(II) oxidase enzymes (NHIOs) such as naphthalene dioxygenase, isopenicillin N synthase and prolyl hydroxylase catalyse a diverse array of oxidation reactions, using the generalised active site environment 2 to activate molecular oxygen. Selected Publications 1. Howard-Jones, AR, Elkins, JM, Clifton, IJ, Adlington, RM, Baldwin, JE and Rutledge PJ. Interactions of isopenicillin N synthase with cyclopropyl-containing substrate analogues reveal new mechanistic insight. Biochemistry, 46, 4755-4762, 2007. 2. Daruzzaman, A, Clifton, IJ, Adlington, RM, Baldwin, JE and Rutledge, PJ. Unexpected oxidation of a depsipeptide substrate analogue in crystalline isopenicillin N synthase. ChemBioChem, 7, 351-358, 2006. 3. Murphy, PV and Rutledge, PJ. Symbiosis in chemistry and biology. Nature Chem. Biol., 2, 59-62, 2006. 4. Rutledge, PJ. Nitriles with a heteroatom attached to the cyanocarbon. Comprehensive Organic Functional Group Transformations II, Volume 5 Jones RCF, Katritzky, AR and Taylor, RJK (Ed.); Elsevier/Pergamon Press, 1023-1080, 2005. 5. Howard-Jones, AR, Rutledge, PJ, Clifton, IJ, Adlington, RM and Baldwin, JE. Unique binding of a non-natural l,l,l-substrate by isopenicillin N synthase. Biochem. Biophys. Res. Comm., 336, 702-708, 2005. 6. Long, AJ, Clifton, IJ, Roach, PL, Baldwin, JE, Rutledge, PJ and Schofield, CJ. Structural studies on the reaction of isopenicillin N synthase with substrate analogues δ-(l-α-aminoadipoyl)-l-cysteinyl-glycine and δ-(l-α-aminoadipoyl)-l-cysteinyl-d-alanine. Biochemistry, 44 6619-6628, 2005. 7. Krall, JA, Rutledge, PJ and Baldwin, JE. Design and synthesis of an isopenicillin N synthase mimic. Tetrahedron, 61, 137-143, 2005. 8. Grummitt, AR, Rutledge, PJ, Clifton, IJ and Baldwin, JE. Active site mediated elimination of hydrogen fluoride from a fluorinated substrate analogue by isopenicillin N synthase. Biochem. J., 382, 659-666, 2004. 9. Elkins, JM, Rutledge, PJ, Clifton, IJ, Burzlaff, NI, Roach, PL, Adlington, RM and Baldwin, JE. Crystallographic investigation of the isopenicillin N synthase reaction with the unsaturated substrate analogue δ-(l-a-aminoadipoyl)-l-cysteinyl-d-vinylglycine. Org. Biomol. Chem. 1, 1455-1460, 2003. 10 School of Chemistry Research Report 12 School of Chemistry Associate Professor Robert S Armstrong Honorary Staff Room 146 School of Chemistry, F11 Telephone: +61 2 9351 3104 Facsimile: +61 2 9351 3329 Email: [email protected] http://www.chem.usyd.edu.au/about/staff_armstrong.html inorganic and bioinorganic spectroscopy Cancer Diagnosis in Tissues and Identification of Microbes by Vibrational Spectroscopy (Ali, Carter, Lay, Johnson, Mountford*, Rich, Russell*, Sorrell*, Tam) Microprobe infrared (IR) and Raman vibrational spectroscopy was used in conjunction with multivariate analysis to develop new diagnostics for breast cancer, and in particular pre-cancerous lesions. IR and Raman images were plotted based on the distributions of diagnostic peaks, including amide I (ν(C=O) at 1650 cm–1), lipid (δ(CH2/CH3) at 1445 cm–1) and DNA (νs(PO2–) at 1240 cm–1). Strong correlations have been obtained for vibrational imaging diagnosis with diagnoses obtained from standard pathology studies and NMR techniques. Vibrational spectroscopic techniques are also being developed to identify pathogenic micro-organisms and to examine their susceptibility to new drugs. XAS and Resonance Raman Studies of Hemes and Heme Proteins (Harris, Lay, Levina, Rich, Witting*) Resonance Raman and EPR spectroscopic and XAFS studies are being used to probe the active sites of heme proteins, and their small molecule adducts. There is particular interest in how these proteins use the binding of NO or other small molecules in signal processes, the immune system, for vasicodilation, and the role they might have in cardiovascular disease. Fullerenes: Their Complexes, Conjugates and Derivatives (Boyd*, Carter, Gallagher, Lay, Reed*, Sen Gupta) Research has continued into studies of the spectroscopy and bioinorganic chemistry of fullerene/porphyrin conjugates, including water-soluble species. These conjugates have been shown to be very potent potential anti-cancer drugs, with higher activity than cisplatin against a series of cell lines, including Pt-resistant lines. The spectroscopy, electrochemistry and coordination chemistry of C60 and C70 are being investigated in detail. Selected Publications 1. Gallagher, SH, Armstrong, RS, Lay, PA and Reed, CA. D-term scattering in the resonance Raman spectrum of C60 J. Am. Chem. Soc., 116, 12091-12092, 1994. 2. Gallagher, SH, Armstrong, RS, Lay, PA and Reed, CA. Resonance Raman spectra of C70 in benzene. Chem. Phys. Lett., 234, 245248, 1995. 3. Gallagher, SH, Armstrong, RS, Clucas, WA, Lay, PA and Reed, CA. Resonance Raman scattering from solutions of C60 J. Phys. Chem., 101, 2960-2968, 1997. Annual Research Report 13 4. Gallagher, SH, Armstrong, RS, Bolskar, RD, Lay, PA and Reed, CA. Raman excitation profiles of C70 in benzene solutions. Assignment of electronic spectrum in the region of 380-510 nm. J. Am. Chem. Soc., 119, 4263-4271, 1997. 5. Rich, AM, Armstrong, RS, Ellis, PJ, Freeman, HC and Lay, PA. Determination of iron–ligand bond lengths in horse heart met- and deoxy-myoglobin using multiple-scattering XAFS analyses. Inorg. Chem., 37, (22), 5743-5753, 1998. 6. Rich, AM, Ellis, PJ, Tennant, L, Wright, PE, Armstrong, RS and Lay, PA. Determination of Fe–ligand bond lengths and the Fe–N–O bond angles in soybean ferrous and ferric nitrosylleghemoglobin a using multiple-scattering XAFS analyses. Biochemistry, 38, 16491-16499, 1999. 7. Bae, IT, Tolmachev, Y, Mo, Y, Scherson, D, Scheidt, WR, Ellison, MK, Cheng, M-C, Armstrong, RS and Lay, PA. In situ Fe Kedge X-ray absorption spectroscopy of a nitrosyl iron(II) porphyrin adduct adsorbed on a high-area carbon electrode in aqueous electrolytes. Inorg. Chem., 40, 3256-3258, 2001. 8. Terentis, AC, Thomas, SR, Takikawa, O, Littlejohn, TK, Truscott, RJW, Armstrong, RS, Yeh, S-R and Stocker, RJ. The heme environment of recombinant human indoleamine 2,3-dioxygenase. Biol. Chem., 277, 15788-15794, 2002. 9. Kim, K-C, Hauke, F, Hirsch, A, Boyd, PDW, Carter, EA, Armstrong, RS, Lay, PA and Reed, CA. Synthesis of the C59N+ carbocation. A monomeric azafullerene isoelectronic to C60. J. Amer. Chem. Soc. Commun., 125, (14), 4024-4025, 2003. 10. Gallagher, SH, Thompson, KC, Armstrong, RS and Lay, PA. The unusual intensity behaviour of the 281-cm−1 resonance Raman band of C60 - a complex tale of vibronic coupling, symmetry reduction, solvatochromism and Jahn-Teller activity. J. Phys. Chem. A., 108, (26), 5564-5572, 2004. 11. Aitken, JB, Thomas, SE, Stocker, R, Thomas, SR, Takikawa, O, Armstrong, RS and Lay, PA. Determination of the nature of the heme environment in nitrosyl indolamine 2,3-dioxygenase using multiple-scattering analyses of x-ray absorption fine structure. Biochemistry, 43, (17), 4892-4898, 2004. 12. Feng, L, Gell, DA, Zhou, S, Gu, L, Kong, L, Min Hu,YJ, Yan, N, Rich, AM, Armstrong, RS, Lay, PA. Gow, AJ, Weiss, MJ, Mackay, JP and Shi Y. Molecular mechanism of AHSP-mediated stabilization of a-hemoglobin. Cell, 119, 629-640, 2004. 13. Immoos, CE, Suic, PJ, Czarnecki, K, Bocian, DF, Levina, A, Aitken, JB, Armstrong, RS and Lay, P. A. Bonding in HNO-myoglobin as characterised by X-ray absorbance and resonance Raman spectroscopies. J. Amer. Chem. Soc., (Communication), 127, 814-815, 2005. 14. Levina, A, Armstrong, RS and Lay, PA. Three-dimensional structure determination using multiple-scattering analysis of XAFS: Applications to metalloproteins and coordination chemistry. Coord. Chem. Rev., 249, 141-160, 2005. 15. Armstrong, RS, Foran, GJ, Hough, WA, D’Alessandro, DM, Lay, PA, Crossley, MJ. Spectroelectrochemical evidence for communication within a laterally-bridged dimanganese(III) bis-porphyrin. J. Chem. Soc., Dalton Trans., 4805-4813, 2006. 14 School of Chemistry Associate Professor Phil Attard* Room 240 School of Chemistry, F11 Telephone: +61 2 9351 5878 Facsimile: +61 2 9351 3329 Email: [email protected] http://www.chem.usyd.edu.au/about/staff_attard.html *ARC Professorial Fellow Annual Research Report 15 reproduced the Green-Kubo time-correlation formulae for the hydrodynamic transport coefficients, which are one of the few formally exact non-equilibrium results already known. Importantly, molecular-level computer simulation algorithms were developed and implemented, and these verified the theory numerically and confirmed its computational feasibility. The theory successfully reproduced literature results for the thermal conductivity of a Lennard-Jones fluid, and it was found to be more efficient than equilibrium molecular dynamics Green-Kubo simulations. This is the first time that a Monte Carlo simulation algorithm has been developed and applied to a non-equilibrium problem. We anticipate that future research in non-equilibrium area will proceed both in the application of the theory and in the analysis of its foundations. In the former case problems such as electrical conduction, driven diffusion, and convection beckon. More fundamentally, extension to transient and non-steady phenomena is called for, as is analysis of non-equilibrium phase transitions, semi-analytic approximations, and computational algorithms. The semi-quantitative exploration of complex systems including life, earth, and beyond is now also possible. thermodynamics, statistical mechanics, and condensed matter theory From Molecular Interactions to Macroscopic Properties Statistical mechanics describes how the cooperative behaviour of molecules determines macroscopic phenomena, and it can be used to unravel a multitude of scientific and industrial problems. We explore the properties of condensed matter at the molecular level using various computational and mathematical techniques, and by collaborative experiments. We emphasise the development of new methods for the treatment of more complex systems, such as inhomogeneous and confined liquids, and specific calculations aimed at rationalising measured data and unexplained phenomena, such as aspects of the interactions of colloidal particles and surfaces. Not only has this resulted in quantitative descriptions of various phenomena, but it has also advanced the understanding and foundations of thermodynamics and statistical mechanic. Theory often consists of the application of pre-existing techniques to specific problems, but we prefer to develop new techniques and algorithms with a view to their broad use and their application to generic classes of systems. Obviously this is more challenging but the reward is in the greater impact of the research. To date we have formulated Monte Carlo and molecular dynamics computer simulation algorithms to obtain the chemical potential, the solvation free energy, the surface tension, and the properties of fluids under shear. We have also developed mathematical techniques such as integral equation and asymptotic expansion and applied them to the electric double layer, to polymer melts, and to near-critical and spinodal fluids. At the continuum level, we have invented mathematical models and algorithms to characterize deformation and viscoelastic effects on particle interactions. Fig. 1 First non-equilibrium Monte Carlo simulation. The thermal conductivity of a Lennard-Jones fluid has been obtained as a function of density using the new non-equilibrium probability density (squares and circles, offset horizontally), and compared to conventional non-equilibrium molecular dynamics literature results (triangles). Nonequilibrium Statistical Mechanics This past year saw us announce a major breakthrough in the study of time-dependent phenomena, namely a general theory for non-equilibrium thermodynamics and statistical mechanics. Ludwig Boltzmann, who died 100 years ago this September, invented the equilibrium probability distribution, exp –U /RT. His grave bears the epitaph, S = kB log Ω , which gives the entropy of an equilibrium system. Until now neither the entropy nor the probability have been known for non-equilibrium or time-dependent systems, and the new theory significantly advances the field by providing expressions for these. The maximisation of the new second entropy generalises the second law of thermodynamics to non-equilibrium systems. The new theory justifies the regression hypothesis of Onsager, which provided the reciprocal relations, and contrasts with the principle of minimum entropy production enunciated by Prigogone, another Nobel prize winner. The significance and generality of the new non-equilibrium theory can be appreciated by its application to the problem of the origin of life and the direction of its evolution. These are both consistent with the new law of thermodynamics even though they paradoxically appear to contradict the conventional second law of thermodynamics. To test and to illustrate the new theory, it was applied to the problem of steady heat flow, which may be thought of as the canonical non-equilibrium problem. It was shown mathematically that in the linear regime the theory Selected Publications 1. Attard, P. Thermodynamics and statistical mechanics: Equilibrium by entropy maximisation. Academic Press, London, 448 pages, 2002. 2. Attard, P. Electrolytes and the electric double layer. Adv. Chem. Phys., 92, 1-159, 1996. 3. Attard, P. Friction, adhesion, and deformation: Dynamic measurements with the atomic force microscope. J. Adhesion Sci. Technol., 16, 753-791, 2002. 4. Stiernstedt, J, Rutland, MW and Attard, P. A novel technique for the in situ calibration and measurement of friction with the atomic force microscope. Rev. Sci. Instrum., 76, 083710, 2005. 5. Attard, P. Statistical mechanical theory for steady state systems. V. Non-equilibrium probability density. J. Chem. Phys., 124, 224103, 2006. 6. Attard, P. Theory for non-equilibrium statistical mechanics. Phys. Chem. Chem. Phys., 8, 1-26, 2006. 16 School of Chemistry Annual Research Report Dr George B Bacskay Selected Publications Honorary Staff Room 315 School of Chemistry, F11 Telephone: +61 2 9351 3777 Facsimile: +61 2 9351 3329 Email: [email protected] http://www.chem.usyd.edu.au/about/staff_bacskay.html quantum chemistry Spectroscopic Properties of C2: Quantum Chemical Computations of Oscillator Strengths and Radiative Lifetimes Quantum (Kokkin, Schmidt) C2 is a prominent molecule in flames, but also in protoplanetory nebulae, comets and interstellar molecular clouds. It is an increasingly important probe of extraterrestrial environments, most recently of the Red Rectangle. The accurate astrophysical modeling of C2 requires detailed and precise understanding of the photophysics of C2. While experimental spectroscopy provides much of the basic data, properties such as oscillator strengths are not readily amenable to direct experimental determination. They can be, however, determined by theoretical approaches, namely by high-level quantum chemical computations. The aims of this project have been the computation of oscillator strengths and other spectroscopic properties, as accurately as currently possible, using state of the art quantum chemical methods, of the d3Pg ← a3Pu Swan band system, the b3Sg- ← a3Pu Ballik-Ramsay band system, the A1Pu ← X1Sg+ Phillips band system and the d3Pu ← c3Sg+ band system. The potential energy surfaces of the electronic states of interest were computed using multi-reference configuration interaction (MR-CI) methods and correlation consistent polarized basis sets ranging from double to hextuple zeta, viz. aug-pVxZ, x = 2,3,... 6, resulting in a high degree of convergence of the valence correlation energy. Core and core-valence correlation corrections were calculated by MR-CI, using the aug-cc-pCVQZ basis. Scalar relativistic corrections were also computed by MR-CI with the cc-pVQZ basis. The bulk of the computations were carried out using the MOLPRO 2006.1 programs on the SGI Altix AC computer of the Australian Partnership for Advanced Computing at the National Supercomputing Centre, ANU. The computed geometries, harmonic frequencies, anharmonicities and rotational constants are in excellent agreement with experiment, e.g. within 0.1 % in case of the harmonic frequencies and rotational constants. The calculated radiative lifetimes of the various vibronic states are also in good accord with the available experimental data. Most importantly, however, this work has yielded a complete series of oscillator strengths for the four band systems studied, which will enable the development of significantly more accurate astrophysical models of C2. Spectroscopic Properties of Halocarbenes The systematic study of halocarbenes in collaboration with A/Prof Kable’s group in the School of Chemistry has been an on-going research activity for almost a decade. Systems, ranging from HCF to CClBr, CBr2 and CF3CF have been characterized via ab initio quantum chemical techniques with regard to their thermochemistry, spectroscopic constants and photochemistry in their ground and lowest triplet and singlet excited states3,7. Such studies have provided a theoretical underpinning to the assignment and interpretation of observed spectroscopic data. This theoretical work is being extended to iodine containing carbenes. The quantum chemical treatment of such molecules requires special techniques so as to reliably describe and account for scalar relativistic and spin-orbit coupling effects. To this end, a variety of effective core potentials and correlation consistent basis sets are explored. Work is in progress on the ICX carbenes (X = F, Cl, Br and I), with an emphasis on the accurate prediction of geometries, vibrational frequencies and excitation energies. 17 1. Eek, W, Nordholm, S and G. B. Bacskay. The screened atomic potential – a simple explanation of the aufbau model.Chem. Educator, 11, 235-242, 2006. 2. Mackie, JC and Bacskay, GB. Quantum chemical study of the mechanism of reaction between NH (X3S¯) and H2, H2O and CO2 under combustion conditions. J. Phys. Chem. A, 109, 11967-11974, 2005. ~ 3. Guss, JS, Bacskay, GB and Kable, SH. Quantum chemical computation of the spectroscopic constants of the X(1A´), ã(3A˝) and 1 Ã( A˝) states of CBrCl and its heat of formation”, Chem. Phys. Letters, 405, 258-264, 2005. 4. Hush, NS, Schamberger, J and Bacskay, GB. A quantum chemical computational study of the relative stabilities of cis- and transplatinum dichloride in aqueous solution. Coord. Chem. Rev., 249, 299-311, 2005. 5. Bacskay, GB and Mackie, JC. Oxidation of CO by SO2: A theoretical study. J. Phys. Chem. A, 109, 2019-2025, 2005. 6. Zhang, F, Bacskay, GB and Kable, SH. Quantum chemical determination of the equilibrium geometries and harmonic vibrational frequencies of 1,1´-, 1,2´- and 2,2´-binaphthyl in their ground and excited (1La) electronic states. J. Phys. Chem. A, 108, 172-184, 2004. 7. Bacskay, GB. Quantum chemical characterisation of the ground and lowest excited singlet and triplet states of CH3CF and CF3CF and their photochemical isomerization and dissociation pathways. Mol. Phys., 101, 1955-1965, 2003. 8. Haworth, NL and G B Bacskay: “Heats of formation of phosphorus compounds determined by current methods of computational quantum chemistry. J. Chem. Phys., 117, 11175-11187, 2002. 18 School of Chemistry Dr Robert W Baker Room 516a School of Chemistry, F11 Telephone: +61 2 9351 4049 Facsimile: +61 2 9351 3329 Email: [email protected] http://www.chem.usyd.edu.au/about/staff_baker.html Annual Research Report 19 Metallocene-Based Catalysts for Olefin Polymerisation and Asymmetric Catalysis (Alt,† Schilling†) Polyolefins are a multi-billion dollar a year industry. Recently, there has been enormous interest in the use of metallocenes as single-site homogeneous cataysts for the polymerisation of olefins. We have prepared a number of unique fluorenebased metallocenes such as the ansa-zirconocene complexes 9 – 11, which have been used as catalysts (in combination with methylalumoxane) for the preparation of polyethylene and stereoregular polypropylene; e.g. highly syndiotactic polypropylene (which cannot be prepared using traditional heterogeneous Ziegler-Natta catalysts) was obtained using complex 9 as the catalyst. We are also currently investigating the preparation of chiral non-racemic versions of these complexes (using our axially chiral cyclopentadienyl ligand design) for use as asymmetric catalysts for synthetic organic transformations. asymmetric catalysis Planar-Chiral Metal Complexes for Asymmetric Catalysis (Whitby*) Asymmetric synthesis, and in particular asymmetric catalysis, remains one of the most active areas of current research in organic chemistry. Planar-chiral cyclopentadienyl metal complexes feature amongst the most successful asymmetric catalysts, but they are often very difficult to prepare in enantiomerically pure form. We have devised a new type of chiral cyclopentadienyl ligand, incorporating axial chirality, which allows the preparation of planar-chiral metal complexes in enantiomerically pure form. We have recently prepared a wide range of axially chiral chelating indene ligands, such as 1– 6, and are currently exploring the preparation of a number of transition metal complexes (e.g. 7 and 8) using these ligands. In addition to our ability to prepare these complexes in enantiomerically pure form, we have observed that the constrained chelation afforded by our ligand design can in some cases generate metal complexes having unusual coordination environments, and therefore potentially unique reactivity. The screening of these complexes for potential applications in asymmetric catalysis is underway. * † Southampton University, U.K. University of Bayreuth, Germany Selected Publications 1. Baker, RW, Foulkes, MA and Taylor, JA. Axially chiral cyclopentadienyl ligands: stereoselective synthesis of 1-substituted-9-(1′naphthyl)fluorenes and retention of axial chirality in the fluorenyl carbanions. J. Chem. Soc., Perkin Trans., 1, 1047, 1998. 2. Baker, RW, Reek, JNH and Wallace, BJ. Asymmetric synthesis of axially chiral 1-(2′-methyl-3′-indenyl)naphthalenes via prototropic rearrangements of stable rotamers of 1-(2′-methyl-1′-indenyl)naphthalenes. Tetrahedron Lett., 39, 6573, 1998. 3. Baker, RW and Wallace, BJ. Enantiospecific synthesis of a planar chiral bidentate indenyl-alkoxide complex of zirconium using an axially chiral indene ligand. Chem. Commun., 1405, 1999. 4. Baker, RW, Foulkes, MA and Turner, P. Enantiospecific synthesis of a planar chiral fluorenylzirconium ansa-metallocene: synthesis and structures of [1-(9-fluorenyl)- and [1-(1-methyl-9-fluorenyl)-2-(2-indenyl)naphthalene]zirconium dichloride. J. Chem. Soc., Dalton Trans., 431, 2000. 5. Baker, RW and Taylor, JA. Synthesis, resolution and rates of racemisation of 1-(2′-methyl-3′-indenyl)-2-naphthylamine and -2naphthol. Tetrahedron Lett., 41, 4471, 2000. 6. Baker, RW, Foulkes, MA, Griggs, M and Nguyen, BN. A new synthesis of 3-substituted-1H-indenes through reaction of o-(bmagnesioalkyl)phenylmagnesium dihalides with carboxylate esters. Tetrahedron Lett., 43, 9319, 2002. 7. Alt, HG, Baker, RW, Dakkak, M, Foulkes, MA, Schilling, MO and Turner, P. Zirconocene dichloride complexes with a 1,2naphthylidene bridge as catalysts for the polymerisation of ethylene and propylene. J. Organomet. Chem., 689, 1965, 2004. 8. Baker, RW, Luck, IJ and Turner, P. Constrained coordination through atropisomerism: Synthesis and structure of an h5:kN-bidentate N,N-dimethylaniline-functionalised indenylruthenium(II) complex. Inorganic Chemistry Communications, 8, (9), 817-820, 2005. 9. Baker, RW, Rea, SO, Sargent, MV, Schenkelaars, EMC, Tjahjandarie, TS and Totaro, A. Enantioselective synthesis of axially chiral 1-(1-naphthyl)isoquinolines and 2-(1-naphthyl)pyridines through sulfoxide ligand coupling reactions. Tetrahedron, 61, (15), 37333743, 2005. 20 School of Chemistry Associate Professor James Beattie Annual Research Report 21 These remarkable surfactant-free emulsions can be reversibly titrated to about pH 5 without breaking. The pH dependence of their zeta potential implies an isoelectric point of pH~4, independent of the identity of the counteranion, whether chloride, iodide or perchlorate. Room 454 School of Chemistry, F11 Telephone: +61 2 9351 3797 Facsimile: +61 2 9351 3329 Email: [email protected] http://www.chem.usyd.edu.au/about/staff_beattie.html colloids and catalysts Electroacoustics Of Colloidal Suspensions (Djerdjev, Franks, Warr) An electroacoustic effect is created when an alternating electric field is applied to a concentrated (> 1 vol%) colloidal suspension. The charge on the particles causes them to jiggle in the field. Because of their density difference from the surrounding fluid this oscillatory motion creates a sound wave of the same MHz frequency as that of the applied electric field. By measuring the phase as well as the amplitude of this sound wave a dynamic mobility spectrum is obtained which can be analysed to give the mean size of the colloidal particles as well as their zeta potential. This development, made in Sydney over the last decade, allows measurements of the properties of many different concentrated colloidal suspensions, which previously could only be studied under dilute conditions by optical methods. As well, new electroacoustic phenomena continue to be revealed. One of these is the direct observation of surface conduction – the conductivity of ions within the stagnant layer or Stern layer close to the particle surface. When the ionic strength of the supporting medium is high (bottom curve in Figure) the phase lag of the dynamic mobility spectrum decreases with frequency as normal. But when the ionic strength is low the applied field is mostly conducted through the ions in the Stern layer, resulting in the maximum in the phase angle shown by the upper curves in the Figure. Our ability to measure concentrated emulsions has enabled us to confirm quantitatively for the first time the long-standing belief that the oil/water interface is negatively charged spontaneously by the autolysis of water and the preferential adsorption of hydroxide ions. We conducted a pH-stat experiment in which the increasing surface area of the emulsion as homogenisation occurred could be correlated with the hydroxide ion adsorbed on the newly formed surface. The very large surface area of the concentrated (2 vol%) emulsion led to a measurable pH drop; maintaining a constant pH gives the total surface charge. Simultaneously measuring the droplet size with the electroacoustics method gives to total surface area, allowing calculation of the surface charge density to be 5 μC cm-2. Catalysts (Masters, Guo) Heterogeneous catalysts are superior if they can be as selective as homogeneous catalysts and remain active over many catalytic cycles. New mixed metal catalysts based on the AlPO-5 and SAPO-5 zeolite structures have been prepared and tested for activity for cyclohexane oxidation at Delft University of Technology and DSM in The Netherlands. The mixed metal catalysts prepared for the first time showed superior activity. Selected Publications 1. Beattie, JK, Hunter, RJ and Zhang, H. Electroacoustic detection of the onset of depletion flocculation of latex dispersions by hydroxyethyl cellulose. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 275, 83-86, 2006. 2. Beattie, JK. The intrinsic charge on hydrophobic microfluidic substrates. Lab on a Chip, 6, 1409-1411, 2006. 3. Djerdjev, AM, Hunter, RJ and Beattie, JK. Self-depletion flocculation of tetralin oil-in-water emulsions. Langmuir, 22, 84-87, 2006. 4. Rowlands, WN, Beattie, JK, Djerdjev, AM and O’Brien, RW. Ultrasonic attenuation by nanoporous particles. Physical Chemistry Chemical Physics, 8, 5124-5130, 2006. 5. Whitby, CP, Djerdjev, AM, Beattie, JK and Warr, GG. Nanoparticle adsorption and stabilisation of surfactant-free emulsions. Journal of Colloid and Interface Science, 301, 342-345, 2006. 22 School of Chemistry Dr Ronald J Clarke Room 358 School of Chemistry, F11 Telephone: +61 2 9351 4406 Facsimile: +61 2 9351 3329 Email: [email protected] http://www.chem.usyd.edu.au/about/staff_clarke.html biophysical chemistry of membranes Mechanism of the Na+,K+-ATPase (Pilotelle-Bunner, Cornelius1, Apell2, Sebban3) The Na+,K+-ATPase, which is found in the plasma membrane of all animal cells, utilizes the free energy derived from ATP hydrolysis for the transport of Na+ ions out of and K+ ions into the cell. The concentration gradients of Na+ and K+ thus generated across the cell membrane have numerous important physiological functions, e.g. maintenance of the resting potential in nerve cells, cell volume regulation and nutrient reabsorption in the kidney. The aim of this project is to determine the kinetics and thermodynamics of the individual reaction steps of the enzyme’s complex reaction cycle and thus obtain a deeper understanding of the mechanism of ion pumping and how it is coupled to ATP hydrolysis. Major tools involved in these investigations are stopped-flow fluorescence spectroscopy, which allows conformational changes and charge translocation steps of the enzyme to be resolved on the millisecond timescale, and isothermal titration calorimetry, which can resolve the heat released in individual reaction steps. Recently we discovered that the Na+,K+-ATPase from kidney occurs in the membrane in dimeric form. This allows the enzyme to have two gears of ion pumping depending on the ATP concentration. It also improves the efficiency of the enzyme and reduces ATP consumption by the cell. Annual Research Report 23 Regulation of the Na+,K+-ATPase (Rasmussen4) The Na+ concentration gradient built up across the membrane is essential in driving numerous physiological processes, including heart muscle contraction and glucose uptake. The enzyme has, thus, been implicated in diseases such as congestive heart failure and diabetes. In order to locate possible mechanisms of in vivo regulation of the enzyme we have been constructing kinetic models of the enzyme’s steady state activity based on the kinetic constants of its partial reactions. The results of such theoretical simulations are then compared to experimental data of the enzyme’s activity obtained from either whole-cell patch clamp measurements performed at the Royal North Shore Hospital on isolated rabbit heart muscle cells or activity measurements on purified membrane preparations. Orientational Polarisability of Membrane Surfaces (Le Goff, Vitha5) The activity of ion pump membrane proteins is known to be very dependent on the composition of the surrounding lipid membrane. The mechanisms by which lipids interact with membrane proteins are, however, unclear. We propose a mechanism whereby dipolar or charged residues in the lipid headgroup region reorientate themselves around highenergy intermediates in the reaction cycle of ion pump proteins. To investigate this hypothesis we have developed a fluorescence method utitilzing the voltage-sensitive probe, di-8-ANEPPS, to measure the orientational polarisability of lipid membrane surfaces. Using our fluorescence method we have recently found that an increase in lipid unsaturation decreases the orientational polarisability, due to a decrease in the polarity at the membrane surface. The incorporation of cholesterol into the membrane was also found to decrease the orientational polarisability but by a different mechanism. Cholesterol causes an ordering of the membrane and a decrease in the range of motion of the lipid head groups. Voltage-Sensitive Fluorescent Membrane Probes (Vitha5) Voltage-sensitive fluorescent membrane probes can be used to determine the magnitude of electric field strengths within lipid membranes and in principle within living cell membranes. We have already developed a technique which is applicable to synthetic lipid vesicles, as a model membrane system. Now our aim is to extend the project to fluorescence microscopy and measure the spatial distribution of electric field strength across membrane surfaces and the fluorescence due to single molecules. University of Aarhus, Denmark Unversity of Constance, Germany 3 Laboratoire de Chimie-Physique, Universite Orsay, France 4 Department of Cardiology, Royal North Shore Hospital 5 Drake University, USA 1 2 Selected Publications 1. Clarke, R. The dipole potential of phospholipid membranes and methods for its detection. Adv. Colloid Interfac. Sci., 89-90, 263281, 2001. 2. Bamberg, E, Clarke, RJ and Fendler, K. Electrogenic properties of the Na+,K+-ATPase probed by presteady state and relaxation studies. J. Bioenerg. Biomem., 33, 401-405, 2001. 3. Kong, BY and Clarke, RJ. Identification of potential regulatory sites of the Na+,K+-ATPase by kinetic analysis. Biochemistry, 43, 2241-2250, 2004. 4. Amoroso, S, Agon, VV, Starke-Peterkovic, T, McLeod, MD, Apell, H-J, Sebban, P and Clarke, RJ. Photochemical behavior and Na+,K+-ATPase sensitivity of voltage-sensitive styrylpyridinium fluorescent membrane probes. Photochem. Photobiol., 82, 495-502, 2006. 5. Starke-Peterkovic, T, Turner, N, Vitha, MF, Waller, MP, Hibbs, DE and Clarke, RJ. Cholesterol effect on the dipole potential of lipid membranes. Biophys. J., 90, 4060-4070, 2006. 6. Le Goff, G, Vitha, MF and Clarke, RJ. Orientational polarisability of lipid membrane surfaces. Biochem. Biophys. Acta – Biomembr., 1768, 562-570, 2007. 7. Hansen, PS, Clarke, RJ, Buhagiar, KA, Hamilton, E, Garcia, A, White C and Rasmussen, HH. Alloxan-induced diabetes reduces sarcolemmal Na+-K+ pump function in rabbit ventricular myocytes. Am. J. Physiol. Cell Physiol., 292, C1070-C1077, 2007. 8. Clarke, RJ, Apell, H-J and Kong, BY. Allosteric effect of ATP on Na+,K+-ATPase conformational kinetics. Biochemistry, in press. 24 School of Chemistry Dr Rachel Codd Room 412c School of Chemistry, F11 Telephone: +61 2 9351 4233 Facsimile: +61 2 9351 3329 Email: [email protected] http://www.chem.usyd.edu.au/about/staff_codd.html Chemical Biology Metalloproteins from Cold-Adapted Bacteria (Simpson, Richardson) The extreme temperatures present on Earth, such as those found in the boiling hydrothermal vents on the ocean floor and in freezing Polar regions, have forced resident bacteria and archaea to adapt to these seemingly inhospitable conditions. Proteins expressed by ‘extremophilic’ life forms have unusual structures and may have applications in biotechnology. Proteins expressed by psychrophilic (‘cold-loving’) bacteria (growth temperature <15 °C), for example, have higher glycine contents, compared to the analogous mesophilic (growth temperature 20-40 °C) proteins. Proteins which are active at modest temperatures offer a novel construct for industrial biocatalytic processes by minimising unwanted side reactions. We are examining the nature of cold-adapted metalloproteins expressed by psychrophilic bacteria isolated from Antarctic sea ice, focusing on metalloproteins that have been characterised in mesophilic and hyperthermophilic (growth temperature > 85 °C) organisms. We have isolated the first-ever characterised cold-adapted redox-active metalloprotein from an Antarctic bacterium (periplasmic nitrate reductase) and have used homology modelling to predict the structure (pictured), based upon our coupled gene sequencing experiments. Novel Resins for Molecular Capture and Resolution (Ejje, Liu) We are developing new chromatographic technologies to capture small molecule metabolites from bacterial cultures. Our technique enables a high-level of control over the types of molecules to be targeted and has wide ranging implications for natural products screening. We are examining ways to synthesise resins that are tailored toward resolution chemistry by immobilising coordination complexes onto resins, using standard coupling techniques. These resins will be well suited toward resolution of many organic ligands, which has increasing significance in pharmaceutical applications, where resolved (100% e.e.) compounds are required for use in clinical trials. Bioinformatics in Chemical Biology (Simpson, Ejje) Ever-expanding genomic data provides an invaluable resource to chemical biologists. This data can be used to predict protein expression and/or structure and can be used to chart likely biosynthetic pathways of small molecule metabolites. We are using bioinformatics to map the biosynthetic pathways of both nonribosomal peptide synthetase (NRPS)-dependent Annual Research Report 25 and NRPS-independent siderophores in bacteria. These studies will enable our judicious selection of bacteria for the isolation of native novel siderophore molecules (see project below). Our genome mining studies have implications in the growing field of medical bioinformatics, focussing upon proteins implicated in human disease to improve the design of therapeutic targets. “Super-Siderophores” From Cold-Adapted Bacteria (Pakchung, Liu) In order to survive in Antarctic regions, resident bacteria must adapt their biomolecular machinery to remain functional under cold conditions (refer to project above). In this project, we are isolating small-molecule organic chelates involved in microbial Fe(III) uptake (siderophores) from Antarctic bacteria grown under conditions of low Fe availability. We hypothesise that cold-adapted siderophores produced by Antarctic bacteria will have novel structures and extraordinary affinities towards Fe(III). Further, we are preparing retroisomers of hydroxamateappended macrocycles as models for cyclised siderophores, such as desferrioxamine E in addition to tagging Fe(III)-siderophore receptor/transport proteins. Metal-Sialic Acid Chemistry (Fainerman-Melnikova, Kiefel) Sialic acids (e.g., N-acetylneuraminic acid; Neu5Ac) are negatively-charged carbohydrates located at cell surfaces that play important roles in cell-recognition processes. We have shown that Neu5Ac (both as the free ligand and as a terminal glycoconjugate) forms complexes with transition metal ions. We are using several spectroscopic techniques to understand the speciation between transition metal ions and Neu5Ac and to probe the effects that these interactions have upon metalion attenuated glycoconjugate misprocessing, of relevance to neurodegenerative diseases, such as Alzheimers disease. A family of organic molecules that model specific regions of Neu5Ac are being prepared to assist in the deconvolution of metal-Neu5Ac speciation profiles. Selected Publications 1. Pakchung, AAH, Simpson, PJL and Codd, R. Life on Earth. Extremophiles continue to move the goal posts (Invited Opening Review for Research Frontier on Extremophiles), Environ. Chem., 3, 77-93, 2006. 2. F a i n e r m a n - M e l n i k o v a , M , C l e g g , J K a n d C o d d , R S . A q u a [ b i s ( 2 - p y r i d y l m e t h y l ) a m i n e ] [ c h e l i d o n a t o (1.5–)]-copper(II) chelidonate(0.5–) monohydrate. Acta Crystallographica Section E-Structure Reports Online, E62, m3582-m3584, 2006. 3. Fainerman-Melnikova, M, Szabó-Plánka, T, Rockenbauer, A and Codd, R. Coordination modes between copper(II) and Nacetylneuraminic (sialic) acid from a 2D-simulation analysis of EPR apectra. Implications for copper mediation of sialoglycoconjugate chemistry relevant to human biology. Inorg. Chem., 44, 2531-2543, 2005. 4. Codd, R. Metalloglycomics: A new perspective upon competitive metal-carbohydrate binding using EPR spectroscopy. Chem. Commun., 2653-2655, 2004. 5. Codd, R. Biomolecules from extremophilic life. In “From Zero to Infinity”. Eds. Nicholls, JA and Pailthorpe, BA, The Science Foundation for Physics, School of Physics, University of Sydney: Sydney, pp 37-48, 2003. 6. Codd, R, McKenny, TM and Freiberg, JA. Insights into metallo-isoenzyme forms of oxotransferases using chemical and biochemical approaches. J. Inorg. Biochem., 96, 119, 2003. 7. Simpson, PJL, Nichols, DS and Codd, RA. Cold-adapted metallo-oxotransferase, periplasmic nitrate reductase, from an Antarctic bacterium. J. Inorg. Biochem., 96, 230, 2003. 26 School of Chemistry Annual Research Report 27 Dr Mark J Coster Toward New AIDS Treatments Based on Inhibition of HIV-1 Integrase (Beare, Fischer, Issa, Burrell*, Li*) Room 518 School of Chemistry, F11 Telephone: +61 2 9351 2752 Facsimile: +61 2 9351 3329 Email: [email protected] http://www.chem.usyd.edu.au/about/staff_coster.html HIV-1 integrase (IN) is responsible for integration of HIV DNA into the host genome, and has recently been identified as a highly promising, yet largely untapped, target for anti-retroviral therapies. Our research is focused on the development of new HIV integrase inhibitors based on two natural product structures, integramycin and lithospermic acid. Our approach to the synthesis of integramycin, for which an ARC Discovery grant was awarded for 2005–7, is modular in nature and should allow biological evaluation of various structural subunits of the natural product. A simple synthetic procedure for accessing the tetramic acid portion of this molecule has been developed and is being further explored. A carbonylative annulation approach to benzofuran analogues of lithospermic acid has proven fruitful and has recently been extended to provide the dihydrobenzofuran portion of lithospermic acid by benzofuran reduction. organic synthesis and stereochemistry Our research interests include: (i) the development of new synthetic methodologies, with a particular emphasis on stereoselectivity; (ii) application of these methods to the synthesis of complex, biologically active natural products, and; (iii) design and synthesis of natural product analogues as potential therapeutic agents. Anti-Cancer Drugs from the Sea: Synthesis of Highly Cytotoxic Marine Macrolides (Cergol, Davidson, Loke, O’Connor, Pigott, Reynolds, Szczepina) Many marine-derived natural products exhibit exceptional levels of biological activity, combined with unique modes of action. However, the pre-clinical and clinical development of marine-derived natural products into pharmaceuticals is often hampered by a limited supply from the natural source. We are currently engaged in synthetic efforts toward two promising marine-derived anti-cancer macrolides, (–)-lasonolide A and amphidinolide H, with the aim to develop efficient syntheses of the natural products and simplified structural analogues for biological evaluation. The lasonolide project was awarded an ARC Discovery grant for 2005–2007, and the amphidinolide H project is funded by a University of Sydney Cancer Research grant for 2004–2005. Progress has been made toward the development of synthetic routes to tetrahydropyran and the dienoate subunits of lasonolide A, while a new metathesis based approach to the difficult 1,3-diene portion of amphidinolide H is under investigation. The Boron-Mediated Ketone–Ketone Aldol Reaction (Cergol, Bacskay, Turner) The first examples of the boron-mediated, cross aldol reaction of ketones were demonstrated in 2004. An investigation of the scope and stereoselectivity of this reaction was completed and efforts are ongoing to complement the experimental work with quantum computational studies of the various possible transition state structures for reactions where high diastereoselectivities were observed. Efforts are ongoing to further explore the scope of this reaction and investigate its potential uses in asymmetric synthesis. Selected Publications Towards the Total Synthesis of Abyssomicin C (Labowitch) The marine-derived natural product, abyssomicin C shows activity against Gram-positive bacteria, including methicillin-resistant S. aureus (MRSA), via a mechanism of action involving inhibition of p-aminobenzoate biosynthesis. Progress has been made in exploring a Diels–Alder based synthetic approach towards the polycyclic core of this molecule. New PET Imaging Agents (Banister, Gunosewoyo, Moussa, Kassiou) This collaborative project is aimed at developing new organic molecules for the imaging of important receptors associated with neurodegenerative disorders, using positron emission tomography (PET) techniques. Current work is aimed at the synthesis of polycyclic hydrocarbon derivatives with potential for use in imaging the P2X7 receptor. 1. Issa, F, Fischer, J, Turner, P and Coster, MJ. Regioselective reduction of 3-methoxymaleimides: An efficient method for the synthesis of 5-hydroxytetramates. J. Org. Chem., 71, 4703-4705, 2006. 2. Cergol, KM, Turner, P and Coster, MJ. The boron-mediated ketone–ketone aldol reaction. Tetrahedron Lett., 46, 1505-1509, 2005. 3. Paterson, I and Coster, MJ. Total synthesis of spongistatin 1 (altohyrtin A): A tale of ten aldols. Strategies and Tactics in Organic Synthesis, Volume 4, Chapter 8, Harmata, M., Ed., Elsevier: Oxford, pp 211-245, 2004. 4. Paterson, I, Aceña, JL, Bach, J, Chen, DY-K, Coster, MJ. Synthesis and biological evaluation of spongistatin/altohyrtin analogues – E-ring dehydration and C46 side-chain truncation. Chem. Commun., 462-463, 2003. 5. Banwell, MG, Coster, MJ, Harvey, MJ and Moraes, J. Selective cleavage of N-benzyl protected 2°-amines by triphosgene. J. Org. Chem., 68, 613-616, 2003. 6. Banwell, MG, Coster, MJ, Karunaratne, OP and Smith, JAA. Chemoenzymatic Synthesis of the Styryllactone (+)-Goniodiol from Naphthalene. J. Chem. Soc., Perkin Trans., 1, 1622-1624, 2002. 7. Coster, MJ and De Voss, JJ. Medium ring ethers by ring expansion-ring contraction: Synthesis of lauthisan. Org. Lett., 4, 30473050, 2002. 8. Paterson, I and Coster, MJ. Total synthesis of altohyrtin A (spongistatin 1): An alternative synthesis of the CD-spiroacetal subunit. Tetrahedron Lett., 43, 3285-3289, 2002. 9. Paterson, I, Chen, DY-K, Coster, MJ, Aceña, JL, Bach, J, Gibson, KR, Keown, LE, Oballa, RM, Trieselmann, T, Wallace, DJ, Hodgson, AP and Norcross, RD. Stereocontrolled total synthesis of (+)-altohyrtin A/spongistatin 1. Angew. Chem. Int. Ed., 40, 4055-4060, 2001. 28 School of Chemistry Professor Maxwell J Crossley, FAA Room 514 School of Chemistry, F11 Telephone: +61 2 9351 2751 Facsimile: +61 2 9351 3329 Email: [email protected] http://www.chem.usyd.edu.au/about/staff_crossley.html Annual Research Report 29 Synthesis and Photophysics of Models for the Photosynthetic Reaction Centre (P. Sintic, Blake, McDonald, Brotherhood, Hutchison*, Ghiggino*, Fukuzumi,* Ohkubo*) Tris-and tetrakis-porphyrin chemical mimics of the chromophore arrangement of the photosynthetic reaction centre (PRC) have been further studied. It was found that complexation of ligands, especially chloride ion, at the zinc(II) site can be used to control the redox driving force for charge separation and the lifetimes of the CS states. In this way very long-lived CS states were observed. The kinetic and thermodynamic properties of the synthetic PRC’s were investigated using ultrafast and ESR spectroscopy and electrochemistry. Singlet-singlet annihilation studies gave further insight into energy transfer in these systems. More elaborate models that incorporate an additional C-60 acceptor unit were designed and synthesised. These are the closest mimics of the natural systems to be developed anywhere. Electrochemistry of Porphyrins (Bond*, Hogan*, Kadish*, Khoury, E*, P. Sintic) Exploration of the redox properties of many different porphyrin-containing systems was undertaken and trends discerned. synthesis of functional organic molecules Porphyrin Arrays As Models For Light-Harvesting Systems And Charge Separation Involved In Photosynthesis (Khoury, Hambly, D’Alessandro, Blake, McDonald, Saito*, Ohkubo*, Fukuzumi*, Sundström*, Canton*, J. Larsen*, White*) Light capture is the first step of photosynthesis. Artificial porphyrin systems designed to mimic light capture in Nature are currently under investigation. These are based on multi-porphyrin arrays assembled on dendrimer cores, designed to mimic the LH1 and LH2 systems and the light-harvesting arrays of Photosystem I. Use of other dendritic cores in the synthesis and their effect on the photophysical properties of resultant porphyrin-appended dendrimers is being explored along with variation of the porphyrin component. Studies of singlet-singlet and triplet-triplet annihilation were carried out. New Advanced Materials (Khoury, Blake, Perry, Fang, Brotherhood, A. Larsen, Chan, Thordarson, Webb, M. Sintic, Stocks, Reimers, Hush) The design and synthesis of new advanced materials based on metalloporphyrins was continued. A novel approach to rigid extended aromatic systems has been further developed to include the synthesis of novel polymers with the potential to behave as electrical conductors and semi-conductors. Studies in the areas of molecular switching devices and molecular shift-registers and novel molecular circuitry were continued. Additional methodology for construction of porphyrin building blocks that allow up to four attachments of molecular wire components was established. New ideas for the development of a non-volatile molecular-scale memory device were further developed and further work was undertaken on design and synthesis of these advanced materials. A means by which multi-directional extension can be made to a porphyrin nucleus was developed and is exemplied by synthesis of the compounds 1 and 2. Porphyrin-Based Photovoltaic Cells (Reimers, Blake, Dastoor*, Fukuzumi*, Hasobe*, Franzon*) A solid-state and a solution photovoltaic cell were constructed using thin films and nano-clusters of porphyrin arrays on optically transparent electrodes as light-harvesting units. Both cells were found to have desirable properties for further investigation. A new approach to aligned donor-acceptor systems was explored. Aggregates formed between porphyrinappended dendrimers and C60 were found to be relatively efficient materials for use in photovoltaic devices. Molecular Recognition in Novel Chiral Bis-porphyrin Cavities (Brotherhood) Compounds with highly selective recognition of dicarboxylic acids were prepared and studied in depth. Porphyrin Analogues as Gingivitis Inhibitors (Simpkins, Yap, Hunter*) The black-pigment Gram-negative bacterium Porphyromonas gingivalis is an important etiological agent of adult periodontal disease. This bacterium has been reported to display an absolute requirement for either hemin or hemoglobin as growth factors. In this year, a second porphyrin-antibiotic conjugate that is recognised by HA2 receptors of the gingipains and is a highly selective inhibitor of the P. gingivitis bacterium has been designed, synthesised, evaluated and patented. Porphyrins in Photonic Crystal Fibres (Martelli*, Canning*, Stocks, M. Sintic) Compounds that form highly ordered monolayers on the interior of optical fibres were synthesised and studied. Selected Publications 1. Crossley, MJ, Thordarson, P, Hunter, N, Yap, B and Collyer, CA. Porphyrin linked metronidazole for treatment of gum disease caused by Porphyromonas Gingivalis. PCT Int. Appl. W02006005137, A1 20060119; CAN 144:128797; AN 2006:54402; 85 pp.  International Classification: (IPC1-7): C07D403/14, 19th January 2006. 2. Hogan, CF, Harris, AR, Bond, AM, Sly, J and Crossley MJ. Electrochemical studies of porphyrin-appended dendrimers, Phys. Chem. Chem. Phys., 8, 2058-2065, 2006. 3. Ohkubo, K, Sintic, PJ, Tkachenko, NV, Lemmetyinen, H, E, W, Ou, Z, Shao, J, Kadish, KM, Crossley, MJ and Fukuzumi, S. Photoinduced Electron-transfer dynamics and long-lived CS states of donor-acceptor linked dyads and a triad containing a gold porphyrin in nonpolar solvents, Chem. Phys., 326, 3-14, 2006. 4. Martelli, C, Canning, J, Stocks, D and Crossley, MJ. Water-soluble porphyrin detection in a pure-silica photonic crystal fibre, Optical Letters, 31, 2100-2102, 2006. 5. Cai, Z-L, Crossley, MJ, Reimers, JR, Kobayashi, R and Amos, RD. Density-functional theory for charge-transfer: The nature of the N-bands of porphyrins and chlorophylls revealed through CAM-B3LYP, CASPT2, and SAC-CI calculations, J. Phys. Chem. B, 110, 15624-15632, 2006. 6. Larsen, J, Brüggemann, B, Polívka, T, Sly, J, Crossley, MJ, Sundström, V, and Åkesson, E. Energy transfer dynamics in Zn-porphyrinappended dendrimers, in Femtochemistry VII: Fundamental Ultrafast Processes in Chemistry, Physics, and Biology, ed. A. Welford Castleman, Jr., Elsevier: Amsterdam, 113-116, 2006. 7. Armstrong, RA, Foran, GJ, Hough, WA, D’Alessandro, DM, Lay, PA and Crossley, MJ. Spectroelectrochemical evidence for communication within a laterally-bridged dimanganese(III) bis-porphyrin, Dalton Trans., 4805-4813, 2006. 8. Larsen, J, Brüggemann, B, Sly, J, Crossley, MJ, Sundström, V and Åkesson, E. Solvent induced control of energy transfer with Zn(II)-porphyrin dendrimers, Chem. Phys. Lett., 433, 159-164, 2006. 9. Brotherhood, PR, Wu, RA-S, Turner, P and Crossley, MJ. Cavity effect amplification in the recognition of dicarboxylic acids by initial ditopic H-bond formation followed by kinetic trapping, Chem. Commun., 225-227, 2007. 10. Kadish, KM, E, W, Zhan, R, Khoury, T, Govenlock, LJ, Prashar, KJ, Sintic, PJ, Ohkubo, K, Fukuzumi, S and Crossley, MJ. Porphyrin-diones and porphyrin-tetraones: Reversible redox units being localized within the porphyrin macrocycle and their effect on tautomerism, J. Am. Chem. Soc., 129, 6576-6588, 2007. 11. Webb, JEA, Crossley, MJ, Turner, P and Thordarson, P. Bisisophthalamide aggregates and their response to anion stimuli, J. Am. Chem. Soc., 129, 7155-7162, 2007. 12. Hulsken, B, van Hameren, R, Gerritsen, JW, Khoury, T, Thordarson, P, Crossley, MJ, Rowan, AE, Nolte, RJM, Elemans, JAAW and Speller, S. Real-time single molecule imaging of oxidation catalysis at a liquid-solid interface, Nature Nanotechnolgy, 2, 285-289, 2007. 13. Hulsken, B, van Hameren, R, Thordarson, P, Gerritsen, JW, Nolte, RJM, Rowan, AE, Crossley, MJ, Elemans, JAAW and Speller, S. Scanning tunneling microscopy and spectroscopy studies of porphyrins at solid-liquid interfaces, Jpn. J. Appl. Phys., 45, 19531955, 2006. 30 School of Chemistry Emeritus Professor Hans C Freeman AM, FAA Honorary Staf Room 146 School of Chemistry, F11 Telephone: +61 2 9351 4504/16028 Facsimile: +61 2 9351 3329 Email: [email protected] http://www.chem.usyd.edu.au/about/staff_freeman.html The structure and function of metalloproteins Many biological processes depend on types of protein, whose molecular structure includes one or more essential metal atoms. Research on the crystal structures of such proteins was initiated in the (then) Department of Inorganic Chemistry in about 1975. An early success was the structure analysis of plastocyanin, a ‘blue’ copper protein with unusual spectroscopic properties and an essential electron-transfer function in photosynthesis. Since then, the structures and amino-acid sequences of plastocyanin from numerous organisms have been reported. A systematic study of these data, aimed at understanding how the proteins of this type evolved, is in progress. Current research on metalloproteins is focused on the crystal structures of auracyanin, a ‘blue’ copper protein from the primitive photosynthetic bacterium Chloroflexus aurantiacus; and copper amine oxidases, a widely distributed class of copper enzymes. In order to explore the mechanism and specificity of the copper amine oxidases, we are undertaking crystal structure analyses of complexes of the enzymes with organic inhibitor molecules, and complexes of the enzymes with electronic ‘wires’. The electronic ‘wires’ are synthetic compounds that can connect a catalytic site buried deep in an enzyme molecule with the external solvent. In addition. they have been shown to be potent inhibitors of the enzymes’ activity. The University’s protein structure laboratory, originally located in the School of Chemistry, was Australia’s first centre for the study of macromolecular crystal structures. It was moved to the Department of Biochemistry (now the School of Molecular and Microbial BioSciences) in 1995. The study of metalloprotein structures is a continuing collaboration with Professor J Mitchell Guss, Director of the Protein Crystallography Laboratory. International collaborators in 2005 included Professor RE Blankenship, Arizona State University, and Dr. M. C. del Rosario, University of California at San Francisco (auracyanin), Professor DM Dooley, Montana State University (amine oxidases), and Professor HB Gray, California Institute of Technology (‘wire’ complexes). Collaborators within the University of Sydney were Dr H. Harris, Chemistry (X-ray absorption spectra), Dr WB Church, Pharmacy (plastocyanin structural comparisons), Dr LS Jermiin and Professor AWD Larkum, Biological Sciences (plastocyanin phylogenetic studies). Selected Publications 1. Freeman, HC. Metalloprotein crystallography. In “Spectroscopic Methods in Bioinorganic Chemistry”, K.O. Hodgson and E.I. Solomon (Eds.), ACS Symposium Series No. 692, American Chemical Society, Washington, Chapter 4, 62-95, 1998. 2. Wilce, MCJ, Bond, CS, Dixon, NE, Freeman, HC, Guss, JM, Lilley, PE and Wilce, JA. Structure and mechanism of a proline-specific aminopeptidase from Escherichia coli. Proc. Natl. Acad. Sci. USA, 95, 3472-3477, 1998. Annual Research Report 31 3. Bond, CS, Bendall, DS, Freeman, HC, Guss, JM, Howe, CM, Wagner, MJ and Wilce, MCJ. The structure of plastocyanin from the cyanobacterium Phormidium laminosum. Acta Cryst., D55, 414-421, 1999. 4. Shi, D, Hambley, TW and Freeman, HC. Crystal structures of three platinum(II)-dipeptide complexes. J. Inorg. Biochem., 73, 173-186, 1999. 5. Bond, CS, Blankenship, RE, Freeman, HC, Guss, JM, Maher, MJ, Selvaraj, FM, Wilce, MCJ and Willingham, KM. Crystal structure of auracyanin, a ‘blue’ copper protein from the green thermophilic photosynthetic bacterium Chloroflexus aurantiacus. J. Mol. Biol., 306, 47-67, 2001. 6. Freeman, HC and Guss, JM. Plastocyanin. In “Handbook of Metalloproteins”, R. Huber, T. L. Poulos and K. Wieghardt (Eds.), Wiley, Chichester, 1153-1169, 2001. 7. Rooney, MB, Honeychurch, MJ, Selvaraj, FM, Blankenship, RE, Bond, AM and Freeman, HC. A thin-film electrochemical study of the ‘blue’ copper proteins, auracyanin A and auracyanin B, from the photosynthetic bacterium Chloroflexus aurantiacus: The reduction potential as a function of pH. J. Biol. Inorg. Chem., 8, 306-317, 2003. 8. Duff, AP, Cohen, AE, Ellis, PJ, Kuchar, JA, Langley, DB, Shepard, EM, Dooley, DM, Freeman, HC and Guss, JM.  The crystal structure of Pichia pastoris lysyl oxidase. Biochemistry, 42, 15148-15157, 2003. 9. Maher, JM, Ghosh, M, Grunden, AM, Menon, AL, Adams, MWW, Freeman, HC and Guss, JM. Structure of the prolidase from Pyrococcus furiosus. Biochemistry, 43, 2771-2783, 2004. 10. Duff, AP, Trambaiolo, DM, Cohen, AE, Ellis, PJ, Langley, DB, Dooley, DM, Guss, JM and Freeman, HC. Using xenon as a probe for dioxygen-binding sites in copper amine oxidases. J. Mol. Biol., 344, 599-607, 2004. 11. Sträter, N, Jasper, B, Scholte, M, Krebs, B, Duff, AP, Langley, DB, Han, R, Averill, BA, Freeman, HC and Guss, JM. Crystal structures of recombinant human purple acid phosphatase with and without an inhibitory conformation of the repression loop. J. Mol. Biol., 351, 233-246, 2005. 12. Contakes, SM, Juda, GA, Langley, DB, Halpern Manners, NW, Duff, AP, Dunn, AR, Gray, HB, Dooley, DM, Guss, JM and Freeman, HC. Reversible inhibition of copper amine oxidase activity by channel-blocking ruthenium(II) and rhenium(I) molecular wires. Proc. Natl. Acad. Sci. USA, 102, 13451-13456, 2005. 13. Duff, AP, Cohen, AE, Ellis, PJ, Hilmer, K, Langley, DB, Dooley, DM, Freeman, HC, Guss, JM. The 1.23Å structure of Pichia pastoris lysyl oxidase reveals a lysine-lysine cross-link. Acta Cryst., D62, 1073-1084, 2006. 14. Langley, DB, Duff, AP, Freeman, HC, Guss, JM. The copper-containing amine oxidase from Arthrobacter globiformis: refinement at 1.55 and 2.20Å resolution in two crystal forms. Acta Cryst., F62, 1052-1057, 2006. 15. Duff, AP, Shepard, EM, Langley, DB, Dooley, DM, Freeman, HC, Guss, JM. A C-terminal disulfide bond in the copper-containing amine oxidase from pea seedlings violates the two-fold symmetry of the molecular dimmer. Acta Cryst., F62, 1168-1173, 2006. 32 School of Chemistry Dr Adrian V George Room 210/223 School of Chemistry, F11 Telephone: +61 2 9351 4413 Facsimile: +61 2 9351 3329 Email: [email protected] http://www.chem.usyd.edu.au/about/staff_george.html synthesis, analysis and education Detection of Steroid Use in Sport (Brooker, Cawley) Dehydroepiandrosterone (DHEA), androst-4-ene3,17-dione (ADIONE), androst-4-ene-3β,17β-diol (4-ADIOL;) and androst-5-ene-3β,17β-diol (5ADIOL), are naturally produced androgens, that may be administered by athletes with the aim of increasing levels of the more active androgens such as testosterone (T) and dihydrotestosterone (DHT). The International Olympic Committee (IOC) prohibits administration of these steroids in athletes; however their detection remains difficult due to an incomplete understanding of metabolism as well as inter-individual variations. In this study, a marker compound that indicates exogenouse abuse of each of these steroids has been found. Confirmation of administration can then be made by use of Gas Chromatography-Combustion-Isotope Ratio Mass Spectrometry (GC-C-IRMS). A study of over 1000 athletes has established a typical range of steroid isotope ratios observed in athletes of different gender, age and ethnic origin. This has allowed a range of carbon isotope ratios to be established that indicate steroid abuse. Improved High-Performance Liquid Chromatography - Tandem Mass Spectrometry (LC-MS/MS) methodology for the quantification and confirmation of synthetic glucocorticosteroid (GCs) abuse in sport has also been developed and validated. Utilizing stable isotopically labeled processed internal standards, the method was used to assess excretion studies from permitted (topical/local) and prohibited (systemic) modes of therapeutic synthetic GC administration. Results from four forms of topical/local administration (dermal, inhalation, nasal spray, heel injection) of the synthetic GC triamcinolone acetonide (TA) showed that all TA excretion was completed within 24 hours, except for the injection study where detection was confirmed for up to four days post-administration. Results from an oral (systemic) administration of triamcinolone (T) showed that the maximum urinary concentration was greater than 3 µg/mL, or more than 100 times the World Anti-doping Agency (WADA) specified (laboratory) minimum required performance limit. This work is being extended to the detection of abuse of endogenous steroid hormones by use of isotope ratio mass spectrometry. Profiling of Synthetic Illicit Drugs (Salouros) Isotope ratio techniques may be used to detect the origin of opium based illicit drugs. This is not satisfactory for synthetic drugs based on amphetamine. Trace impurities in clandestine manufactured drugs are the result of a number of reasons. They can be due to impurities being present in the precursors, solvents and/or reagents which can be carried Annual Research Report 33 over into the final product unchanged or they can react and be transformed into other products. Impurities can also be generated as by-products in the drug manufacturing process. Finally the conditions of storage, such as exposure to light and heat, as well as cutting agents introduced may affect the drug and/or impurities, thus introducing new impurities. Research is being undertaken to link the impurity profile in a reaction with method and conditions of synthesis. This will enable a ‘finger print’ of a synthetic approach to be established and, ultimately, provide a method to determine the origin of batches of seized drugs. Education in Chemistry (Masters, Read, Schmid, Yeung) Detailed analysis, both qualitative and quantitative, of examination scripts from some first year chemistry units has been undertaken.  When combined with qualitative data from students about their experiences and perceptions, a number of interesting questions can be addressed.  Firstly, the question of the extent to which the outcomes from our current assessment system are a reflection of students’ understanding can be examined.  Analysis of students’ approaches to examination questions provides information about both misconceptions held and overall motivations and goals (performance orientation versus mastery orientation).  Such information can be used not only to improve teaching in areas of student difficulty, but can also inform curriculum design more generally, with the ultimate goal of promoting deeper student understanding of the material under study. Secondly, the analysis provides data that supports the common belief that organic chemistry is an area that some students simply ‘don’t get’.  The existence of barriers to deeper understanding of organic chemistry has been proven, and the nature of these barriers examined.  Such information has obvious implications for improving teaching and learning in this fundamental area of chemistry, although more work in this area is needed.  In another project the connection between a person’s learning style (eg whether they prefer to learn in group situations or ‘go it alone’) and they way they interact with different leaning situations is probed. In particular whether the personalization of text (where the material is presented in a conversational style) results in different learning outcomes compared to a more traditional impersonalized presentation. Organometallic Catalysis (Frey, Gardiner) The project aim is to use the porphyrinogen and calixpyrrole structure as a ligand for metals engaged in catalysis reactions. By providing a cavity for the metal we intend to extend the lifetime of the catalyst and have the ability to modify the reactivity of the metal through a variety of interactions with the calixpyrrole host. Large radii lanthanoid metals, such as samarium, have been coordinated in the cavity. Syntheses of a range of these cavity materials has been developed. Selected Publications 1. Cawley, AT, Hine, ER, Trout, GJ, George, AV and Kazlauskas, R. Searching for new markers of endogenous steroid administration in athletes: “Looking outside the metabolic box”. Forensic Science International, 143 (103), 2004. 2. George, AV, Cawley, AT, Kazlauskas, R, Trout, GJ and Rogerson, JH. Isotopic fractionation of endogenous anabolic androgenic steroids and its relationship to doping control in sports. Journal of Chromatographic Science, 43 (1), 32-38, 2005. 3. George, AV, Cawley, AT, Kazlauskas, R and Trout, GJ. Determination of urinary steroid sulfate metabolites using ion paired extraction. Journal of Chromatography B-Analytical Technologies in the Biomedical and Life Sciences, 825 (1), 1-10, 2005. 4. Youl, DJ, Read, JR, George, AV, and Schmid, S. (2006). Bridging courses: Good learning environments for engaging students? 9th Pacific Rim First Year in Higher Education (FYHE) Conference: ‘Engaging Students’. Griffith University in conjunction with Queensland University of Technology, Gold Coast, 12-14 July 2006.  Available from http://www.fyhe.qut.edu.au. ISBN 0-646-46313-6. 5. Yeung, A, George, AV, King, MM, Schmid, S. (2006) Testing the personalisation hypothesis in pre-laboratory e-learning environments. In Symposium Proceedings: Assessment in Science Teaching and Learning. Sydney, NSW: UniServe Science, 146 – 152. Available from http://science.uniserve.edu.au/pubs/procs/2006/yeung.pdf. ISBN 1-86487-865-7. 34 School of Chemistry Professor Robert G Gilbert, FAA Room 351 School of Chemistry, F11 Telephone: +61 2 9351 3366 Facsimile: +61 2 9351 3329 Email: [email protected] http://www.chem.usyd.edu.au/about/staff_gilbert.html polymer colloids Polymers and Emulsion Polymerization: Novel Structure and Properties (Castignolles, Sangster, Vosloo, Thickett, Aungsupravate, Sharma, Koh, Mange, Seabrook, Leswin, Youssef, Taylor, Li). The relationship between molecular and mesoscopic structure on the one hand and mechanical and other end-use properties on the other is a major unsolved problem in polymer colloids. The study of how changes at the molecular level affect physical properties incorporates projects ranging from the preparation of novel nanoparticles to the development of new methods for living radical polymerization in emulsion systems, including both surface coatings (paints etc.) and barrier products (surgical gloves, etc.). Other ongoing projects include the preparation of nanoscale particles through emulsion polymerization, synthesis and characterization of novel polymer colloids with grafted and branched architectures, effects of molecular architecture on mechanical properties (with University of Queensland and the preparation of next-generation environmentally-friendly surface coatings (with Dulux Australia). Fundamental investigations have explored the effect of mobile surfactants and electrosteric stabilizers on the kinetics of particle growth and formation, as well as examining their effects on the end-use properties of surface coatings derived from polymer latices. Studies have been completed on the effect of grafted in-situ stabilizer on the effect of entry and exit of monomeric polymeric radicals. Work continues on the fundamental science of free radical polymerization with a project on reversible addition-fragmentation chain transfer using emulsion polymerization and involvement in IUPAC initiatives to develop more rigorous protocols for determination of propagation and termination rate coefficients. Polymer Colloids in Natural Systems (Gaborieau, Hernandez, Ward, Cuevas, Willoughby, Chang) The aims of this project are to apply the experimental and theoretical techniques developed for the characterization of synthetic polymer colloids to natural polymers. This is leading to the development of models for the molecular architecture of starch hydrocolloids and starch biosynthesis. Theoretical and experimental work is being carried out on obtaining and interpreting reliable data on branched biopolymers, especially starchesExtensive new knowledge has been produced on how the molecular weight distribution of starches affects physical properties such as “mouth-feel”, and how these molecular weight distributions may be used to infer biological pathways in starch synthesis (with the International Rice Research Institute in Manila, and the CRC for Quality Rice and NSW Agriculture). The last-named work has produced the exciting discovery which will enable rice breeders to understand why two apparently very similar varieties of rice grain have very different cooking properties: a result of major importance to farmers. Selected Publications 1. Castignolles, P, Gaborieau, M, Hilder, EF, Sprong, E, Ferguson, CJ and Gilbert, RG. High-resolution separation of oligo(acrylic acid) by capillary zone electrophoresis. Macromolecular Rapid Communications, 27, 42-46, 2006. 2. Chang, JC, Gurr, GM, Fletcher, MJ and Gilbert, RG. Structure–property and structure–function relations of leafhopper (Kahaono montana) silk. Australian Journal of Chemistry, 59, 579-585, 2006. 3. De Bruyn, H, Sprong, E, Gaborieau, M, David, G, Roper, JA, Gilbert, RG. Starch-graft-Copolymer Latexes Initiated and Stabilized by Ozonolyzed Amylopectin. Journal of Polymer Science: Part A: Polymer Chemistry, 44, 5832-5845, 2006. Annual Research Report 35 4. Gilbert, RG. Particle formation by self-assembly in controlled radical emulsion polymerizations. Macromolecules, 39, 4256-4258, 2006. 5. Mock, EB, De Bruyn, H, Hawkett, BS, Gilbert, RG and Zukoski, CF. Synthesis of anisotropic nanoparticles by seeded emulsion polymerization. Langmuir, 22, 4037-4043, 2006. 6. Perry, PA, Fitzgerald, MA and Gilbert, RG. Fluorescence recovery after photobleaching as a probe of diffusion in starch systems. Biomacromolecules, 7, 521-530, 2006. 7. Prescott, SW, Ballard, MJ, Rizzardo, E and Gilbert, RG. Rate optimization in controlled radical emulsion polymerization using RAFT. Macromolecular Theory and Simulations, 15, 70-86, 2006. 8. Ratinac, KR, Gilbert, RG, Ye, L, Jones, AS and Ringer, SP. The effects of processing and organoclay properties on the structure of poly(methyl methacrylate)–clay nanocomposites. Polymer, 47, 6337-6361, 2006. 9. Save, M, Guillaneuf, Y and Gilbert, RG. Controlled radical polymerization in aqueous dispersed media. Australian Journal of Chemistry, 59, 693-711, 2006. 10. Sprong, E, Leswin, JSK, Lamb, DJ, Ferguson, CJ, Hawkett, BS, Pham, BTT, Nguyen, D, Such, CH, Serelis, AK and Gilbert, RG. Molecular watchmaking: ab initio emulsion polymerization by RAFT-controlled self-assembly. Macromolecular Symposia, 231, 84-93, 2006. 11. Thickett, SC and Gilbert, RG. Mechanism of radical entry in electrosterically stabilized emulsion polymerization systems. Macromolecules, 39, 6495-6504, 2006. 12. Thickett, SC and Gilbert, RG. Rate-controlling events for radical exit in electrosterically stabilized emulsion polymerization systems. Macromolecules, 39, 2081-2091, 2006. 13. van Berkel, KY, Russell, GT and Gilbert, RG. The dissociation rate coefficient of persulfate in emulsion polymerization systems. Polymer, 47, 4667-4675, 2006. 14. Ward, RM, Gao, Q, de Bruyn, H, Gilbert, RG and Fitzgerald, MA. Improved methods for the structural analysis of the amyloserich fraction from rice flour. Biomacromolecules, 7, 866-876, 2006. 36 School of Chemistry Professor Trevor W Hambley Room 412a School of Chemistry, F11 Telephone: +61 2 9351 2830 Facsimile: +61 2 9351 3329 Email: [email protected] http://www.chem.usyd.edu.au/about/staff_hambley.html medicinal inorganic chemistry Tuning the Chemistry of Platinum(IV) Drugs (Alderden, Callaghan#, New) Platinum(IV) complexes are more inert than their Pt(II) analogues and therefore have the potential to be less toxic. Fluorescent tags were attached at the leaving and non-leaving group positions of Pt(II) complexes, and to the axial position of a Pt(IV) cisplatin-based complex. The fluorescence of all fluorophores was quenched partially or fully on binding to platinum. The axially-substituted complex exhibited a reduction potential in the range of cytotoxic Pt(IV) complexes, and treatment with cysteine and ascorbic acid led to an increase in fluorescence, consistent with reduction and release of the fluorophore. This confirms the potential of such complexes as fluorescent probes of the reduction event. Annual Research Report 37 Trans-platinum complexes are generally therapeutically inactive, but attachment of bulky amines generates active complexes. A transplatin analogue containing the fluorophore 7-azaindole was synthesised, and found to have a trans activating effect. This complex is therefore a suitable fluorescent model for the study of active trans‑platinum complexes. A2780 ovarian cancer cells were treated with cis­- and trans‑substituted azaindole complexes and visualised by two-photon confocal fluorescence microscopy. The preliminary images obtained reveal the appearance of fluorescence in cells over a period of time, suggesting cleavage of the fluorophore from the complex. These results confirm that coordination state sensitive fluorescence is a promising technique for probing the uptake and metabolism of platinum complexes within cells, and highlight modifications to the fluorophores which will enable more sensitive studies. Selective Targeting of Solid Tumours using Cobalt Complexes (Yamamoto) The goal of our work is to develop new agents that selectively target solid tumours by taking advantage of the differences between tumours and healthy tissues. The specific aims of this project are to develop new cobalt-based hypoxia-selective agents and to modify such agents to achieve the desired level of targeting. In order to do this, we are developing new methods for determining the oxidation state of the hypoxia-selective agents and to investigate their fate in solid tumours and in models of this environment. The rational development of hypoxia-selective agents has been hampered by a lack of knowledge of where and when the agent is reduced and the cytotoxic ligand released. We have investigated cobalt complexes with ligands attached that become fluorescent on release the first time this approach has been used to monitor the loss of ligands from cobalt complexes. The damping of fluorescence on coordination to cobalt(III) is so great that the complex is effectively non-fluorescent. The appearance of fluorescence indicates the separation of the ligand from the complex, either as a result of reduction or ligand loss. In either case, we are able to monitor the critical event in the delivery of a cytotoxin within a tumour cell by visually monitoring where and when the fluorescence appears. Using this technique, we have shown that coumarin-343, coumarin-343 hydroxamate and their cobalt(III) complexes have dramatically different distribution patterns in A2780 ovarian cancer cells. The ability of such fluorescence based methods to report on the release of ligands in solid tumours and tumour models is the next stage of this study and is expected to reveal the potential of cobalt complexes to target the hypoxic regions of solid tumours. The Distribution of Platinum Complexes in Cells and Tumours (Alderden, Whan, Zhang) The development of new metal-based drugs that reach all regions of a tumour has been limited by our ability to track the uptake of the complex. However, the use of fluorophore tagged complexes offers a solution to this problem and we and others have been using anthraquinone tagged platinum complexes to study uptake in cells. These studies show that the tag modifies the properties of the platinum moiety, resulting in increased uptake into the cell, but perhaps also increased disposition to subcellular organelles such as lysosomes (below) and modified cytotoxicity. For instance, Pt1C3 (see right) has the potential to form covalent (coordinate) bonds with DNA in the same way as cisplatin, but can also bind non-covalently with the anthraquinone intercalated between the DNA bases. MTT cytotoxicity assays with A2780 human ovarian carcinoma cells reveals that Pt1C3 has a cytotoxicity that is similar to that of cisplatin after 72 h drug exposure, though interestingly it is more active than cisplatin is after 24 h, when its cytotoxicity is similar to that of 1C3 itself. Thus, Pt1C3 displays the cell killing features of both the intercalator and the platinum moiety which may be advantageous in achieving high efficacy against a non-uniform cell population. The cell killing properties of these compounds is reflected in their subcellular distribution which has features associated with both the platinum and intercalator (below), demonstrating the value of being able to visualize the distribution. What is needed is to establish whether these same visualization techniques can be used to monitor the uptake in solid tumours and tumour models and thereby contribute to the optimization of the properties needed to give improved uptake throughout a tumour. Confocal images of A2780 cells showing: top row; the fluorescence due to coumarin-343 blue) overlaid with the fluorescence due to the nuclear stain SYTO® 21 (green) and bottom row; the fluorescence due to [Co(coumarin343)2(cyclam)]ClO4 (blue) overlaid with the fluorescence due to the nuclear stain SYTO® 21 (green) Targeting of Metastatic Tumours using MMP Binding Agents (Doan, Guenther, Kassiou) Almost all compounds used in the treatment of cancer cause serious side effects because they lack selectivity for tumours. However, the rapidly increasing knowledge and understanding of the differences between the chemistry and biochemistry of tumours and healthy tissues means that it is now possible to envisage drugs that act selectively on tumours. Our work is aimed at developing new agents that selectively target solid tumours by taking advantage of these differences. An important difference that has emerged relatively recently is the overexpression of matrix metalloproteinases (MMPs) in metastasising tumours. The synthesis of a range of novel MMP binding agents with the ability to carry therapeutic and/or imaging radionuclides was begun. Selected Publications Confocal images of A2780 cells showing the fluorescence due to [Pt(dien)1C3] (red) overlaid with the fluorescence due to the nuclear stain SYTO® 21 (green) revealing uptake in lysosomes and limited uptake in the nuclei. 1. A Co(III) complex of the MMP inhibitor marimastat: a potential hypoxia activated prodrug. T.W. Failes, C. Cullinane, C.I. Diakos, N. Yamamoto, J.G. Lyons, and T.W. Hambley. Chemistry, A European Journal, , 13, 2974-2982, 2007. 2. Cytotoxic efficacy of an anthraquinone linked platinum anticancer drug. R.A. Alderden, H.R. Mellor, S. Modok, T.W. Hambley, and R. Callaghan. Biochemical Pharmacology, 71, 1136-1145, 2006. 38 School of Chemistry Professor Margaret M Harding Honorary Staff School of Chemistry, F11 Telephone: +61 2 9351 4504 Facsimile: +61 2 9351 3329 Email: [email protected] http://www.chem.usyd.edu.au/about/staff_harding.html biological and medicinal chemistry Annual Research Report 39 cellular uptake relative to other neutral and polar thiol derivatives of molybdocene dichloride previously studied, the derivative is predicted to show reduced cellular uptake. The results show that incorporation of electron withdrawing groups on the aromatic rings of thiol ligands is insufficient to achieve hydrolysis within hours, and strongly suggests that if a lipophilic analogue can be prepared that retains the trifluoroethane thiol fragment, high cell uptake followed by slow hydrolysis can be achieved in cells. DNA Nanshuttles (Lee, Saccavini, Rendina) Molecular clefts derived from the dibenzobicyclo[b,f][3.3.1]nona-5a,6a-diene-6,12-dione framework contain a rigid angular backbone and a chiral cavity by virtue of the bridgehead structure. Tunable handles in the form of the dione and aryl groups allow for functionalization and structural modification of these clefts. Synthesis, functionalization and resolution of some of these clefts have been recently reported. by our group. These structural features provide the ideal platform for construction of metallosupramolecular nanosquares with tailored or programmed properties. A range of clefts of varying dimensions with pyridyl groups installed at the distal arms have been designed and synthesized, using standard cross-coupling methodologies (Suzuki and Sonogashira reactions). The preparation of water-soluble derivatives (via installation of polyols for example) and the assembly of water-soluble metallomacrocycles allows entry into a new classs of metallomacrocycles that encircle DNA, a binding mode that is utilised by Nature with toroidal proteins, but is unprecedented in synthetic chemistry. Selected Publications Antifreeze Proteins and Glycoproteins (Turner, Inglis, Price*) Antifreeze proteins (AFPs) and glycoproteins (AFGPs) permit many species of fish to survive in sub-zero oceans without freezing. These antifreeze compounds have potential applications in the frozen food industry (eg. maintaining the texture of ice cream), medical science (eg., cryosurgery) and veterinary science (eg. storage of sperm). Commercial applications are limited by the amounts of compounds available from fish and the lack of understanding of how these proteins work. Pulsed Field Gradient Spin Echo NMR Spectroscopy was used to measure diffusion coefficients of the a-helical type I antifreeze protein from the winter flounder, two synthetic derivatives in which the four Thr residues were replaced with Val and Ala respectively, and the low molecular weight fraction antifreeze glycoprotein. Under the conditions studied, the natural type I antifreeze protein and low molecular weight glycoprotein gave diffusion values that were consistent with the presence of monomeric protein in solution. While significant aggregation of the Ala analogue was observed (2-10 mM), there was no evidence for aggregation in the Val analogue (1-3 mM). These results correlate well with solubilitydata and thermal hysteresis data and have important implications for the design of synthetic antifreeze proteins. Organometallic Anticancer Agents (Waern, Dillon) A range of molybdocene derivatives were designed to probe the importance of solubility, charge and the lability of the Mo-X bond on cell uptake and cytotoxicity and hence to provide fundamental data that is essential to assess whether Cp2MoCl2, or metal complexes based on this framework, are promising lead compounds for the development of molybdocene-based anticancer drugs. These first structure activity studies on molybdocene dichloride established that the labile Mo–Cl bonds in Cp2MoCl2 are a requirement for activity. Incorporation of thiols in place of the halogen ligands provides access to stable, water soluble derivatives, some of which are able to enter cells, but that lack the cytotoxicity of the parent complex. Incorporation of the electron-withdrawing fluorinated aromatic rings into the structure resulted in more labile ligands, though not on a time scale to be relevant inc cells. The distinct cytotoxicity and cell uptake profiles of Cp2MoCl2 compared with Cp2Mo(GS)2 show that while rapid coordination of Cp2MoCl2 to glutathione occurs in water at pH 7, this interaction is not significant in cell culture media and that other transport mechanisms are involved in vitro and in vivo. The design, synthesis, and hydrolytic stability of thiol derivatives incorporating electron withdrawing substituents was completed. These derivatives were studied in order to evaluate the effect of the trifluoromethyl groups on the stability of the Mo–S bond, and thus provide fundamental data needed to guide the design of potential prodrugs of Cp2MoCl2 that hydrolyze on an hour timescale to release the active “Cp2Mo2+” species in the cell. The hydrolysis of the trifluoroethane thiol ligands clearly demonstrates that the incorporation of a trifluoromethyl group one carbon away from the Mo–S bond results in increased lability of the Mo–S bonds in molybdocene derivatives Cp2Mo(SR)2. In aqueous DMSO, the rate of hydrolysis (approximately 50% in 14 h) is on a time-scale that is potentially useful in the design of prodrugs of Cp2MoCl2. However as this complex lacks the lipophilic aromatic groups, which exhibited high 1. Liepinsh, E, Otting, G, Harding, MM, Ward, LG, Mackay, JP and Haymet, ADJ. Solution structure of a hydrophobic analogue of the winter flounder antifreeze protein. European Journal of Biochemistry, 264, 1269-1266, 2002. 2. Fairley, K, Westman, BJ, Pham, LH, Haymet, ADJ, Harding, MM and Mackay, JP. Type I shorthorn sculpin antifreeze protein: Recombinant synthesis, NMR spectroscopy & ice growth inhibition properties. Journal of Biological Chemistry, 277, 24073-24080, 2002. 3. Tomczak, MM, Hincha, DK, Crowe, JH, Harding, MM and Haymet, ADJ. The effect of hydrophobic analogues of the type I winter flounder antifreeze protein on lipid bilayers. FEBS Letters, 551, 13-19, 2003. 4. Harding, MM, Anderberg, PI and Haymet, ADJ. “Antifreeze” glycoproteins from polar fish. European Journal of Biochemistry, 270, 1381-1392, 2003. 5. Waern, JB and Harding, MM. Coordination chemistry of the antitumor metallocene molybdocene dichloride with biological ligands. Inorganic Chemistry, 43, 206-213, 2004. 6. Harding, MM, Waern, JB and Dillon, CT. Organometallic anticancer agents: Cellular uptake and cytotoxicity studies on thiol derivatives of the antitumor agent molybdocene dichloride. Journal of Medicinal Chemistry, 48, (6), 2093-2099, 2005. 7. Kwan, A-H, Fairley, K, Anderberg, PI, Liew, CW, Hardingm MM and Mackay, JP. Solution structure of a recombinant type I sculpin antifreeze protein: the effects of supercooling and acetylation. Biochemistry, 44, 1980-1988, 2005. 8. Campbell, KS, Foster, AJ, Dillon, DT and Harding, MM. Genotoxicity and transmission electron microscopy studies of molybdocene dichloride. Journal of Inorganic Biochemistry, 100, 1194-1198, 2006. 9. Inglis, SR, McGann, MJ, Price, WS and Harding, MM. Diffusion NMR studies on fish antifreeze proteins and synthetic analogues. FEBS Letters, 580, 3911-3915, 2006. 10. Lee, CKY, Groneman, JL, Turner, P, Rendina, LM and Harding, MM. Synthesis and x-ray crystallographic analysis of chiral pyridyl substituted carbocyclic molecular clefts. Tetrahedron, 62, 4870-4878, 2006. 11. Waern, JB, Turner, P and Harding, P. Synthesis and hydrolysis of thiol derivatives of molybdocene dichloride incorporating electron-withdrawing substituents. Organometallics, 25, 3417-3421, 2006. 40 School of Chemistry Dr Hugh Harris Room 516 School of Chemistry, F11 Telephone: +61 2 9351 2745 Facsimile: +61 2 9351 3329 Email: [email protected] Sulfite Oxidase (George*, Rajagopalan*) Human sulfite oxidase catalyzes the two-electron oxidation of sulfite to sulfate, a vital step in the catabolism of sulfur containing amino acids. This occurs at a molybdenum centre which is reduced from MoVI to MoIV in the process. The molybdenum is coordinated by the ene-1,2-dithiolate of the molybdopterin cofactor and a protein based cysteine thiolate plus two oxo ligands in the MoVI form, one of which is converted to hydroxide or water in the MoIV form. As yet, the precise functional role of each of the ligands to the metal is not clear. We have combined high resolution EXAFS with DFT calculations to identify the O-donor ligand in the reduced form as water and not hydroxide. Oxidized bioinorganic chemistry Structure of the Cu-binding Domain of the Amyloid Precursor Protein (Parker*) Alzheimer’s disease is thought to be triggered by the production of the peptide Aβ generated through proteolytic cleavage of the amyloid precursor protein (APP). APP can function as a metalloprotein for Cu transport into and out of cells using its Cu-binding domain (CuBD). Cu binding to CuBD reduces the production of Aβ. Thus a mimic of Cu action may have therapeutic potential. We have determined the structures of the apo, Cu+ and Cu2+ forms of CuBD using XRD, XAS and EPR. These reveal only small conformational changes in the Cu-binding site for the Cu-bound forms compared to the apo structure. The site resembles a Type 2 non-blue Cu centre. We have proposed a model to explain how Cu binding leads to decreased Aβ production. Imaging the Biotransformation of Arsenic in a Hyperaccumulating Fern (George*, Pickering*) The fern Pteris vittata accumulates unusually high levels of arsenic. Using X-ray absorption spectroscopy (XAS) and XAS imaging, we have revealed the distribution of arsenic species in vivo. Arsenate is transported through the vascular tissue from the roots to the fronds (leaves), where it is reduced to arsenite and stored at high concentrations. Arsenic-thiolate species surrounding veins may be intermediates in this reduction. In gametophytes, arsenite is compartmentalized within the cell vacuole. Arsenic is excluded from cell walls, rhizoids and reproductive areas. This study provides important insights into arsenic hyperaccumulation and demonstrates the strengths of XAS imaging for distinguishing highly localized species. [arsenite] [arsenate] 41 Annual Research Report Reduced Selected Publications 1. Harris, H, Fisher, K and Dance, I. Coordination and dehydrogenation of PH3 by 23 transition metal ions in the gas phase: FTICR experiments and density functional interpretations. Inorg. Chem., 40, 6972-6982, 2001. 2. Brown, KR. Keller, GL. Pickering, IJ. Harris, HH. George, GN and Winge, DR. Structures of the cuprous-thiolate clusters of the Mac1 and Ace1 transcriptional activators. Biochemistry, 41, 6469-6476, 2002. 3. George, GN, Pickering, IJ, Harris, HH, Gailer, J, Klein, D, Lichtmannegger, J and Summer K-H. Thiomolybdate causes formation of copper-molybdenum clusters in an animal model of Wilson’s disease. J. Amer. Chem. Soc., 125, 1704-1705, 2003. 4. Harris, HH, Pickering, IJ and George, GN. The chemical form of mercury in fish. Science, 301, 1203, 2003. 5. Sneeden, EY, Harris, HH, Pickering, IJ, Prince, RC, Johnson, S, Li, X, Block, E and George, GN. The sulfur chemistry of Shiitake mushroom. J. Amer. Chem. Soc., 126, 458-459, 2004. 6. George, GN, Prince, RC, Gailer, J, Buttigieg, GA, Denton, MB, Harris, HH, and Pickering, IJ. Mercury binding to the chelation therapy agents DMSA and DMPS and the rational design of custom chelators for mercury. Chem. Res. Toxicol., 17, 999-1006, 2004. 7. Harris, HH, Levina, A, Dillon, CT, Mulyani, I, Lai, B, Cai, Z and Lay, P. Time dependent uptake, distribution and biotransformation of chromium(VI) in individual human lung cells: Application of synchrotron radiation techniques. J. Biol. Inorg. Chem., 10, 105-118, 2005. 8. Levina, A, Harris, HH and Lay, PA. Binding of chromium(VI) to histones: Implications for chromium(VI)-induced genotoxicity. J. Biol. Inorg. Chem., 11, 225-234, 2006. 9. Harris, HH, George, GN and Rajagopalan, KV. High-resolution EXAFS of the active site of human sulfite oxidase: Comparison with density functional theory and x-ray crystallographic results. Inorg. Chem., 45, 493-495, 2006. 10. Milsmann, C, Levina, A, Harris, HH, Foran, GJ, Turner, P and Lay, PA. Charge distribution in chromium and vanadium catecholato complexes: X-ray absorption spectroscopic and computational studies. Inorganic Chemistry, 4743-4754, 2006. 11. Harris, HH and Dance, IG. Iron-carbon clusters: Geometric structures and interconversions. Polyhedron, 26, 250-265, 2007. 42 School of Chemistry Professor Peter R Harrowell Room 316 School of Chemistry, F11 Telephone: +61 2 9351 4102 Facsimile: +61 2 9351 3329 Email: [email protected] http://www.chem.usyd.edu.au/about/staff_harrowell.html Annual Research Report 43 Structure and Stability of Ionic Clusters and Reverse Micelles (Wootton) Small clusters represent a fascinating window onto how atoms and molecules behave at surfaces and the enhanced possibilities for structures once long range order is no longer necessary. Using computer simulations we are currently studying the following three questions. i) Can ions form polyhedral clusters that are stable with respect to crystal fragments? ii) How are ion clusters hydrated by water? iii) What is the structure and phase behaviour of small clusters of liquid crystal forming molecules? A systematic study of silver halide clusters has indicated that polyhedral clusters (ionic analogues of buckyballs) are stable when the anion is considerably larger than the cation. A study of clusters of hard sphere monovalent ions showed how custers convert from polyhedra to crystal fragments as the cluster size increases. Reverse micelles formed from ionic surfactants are, at low water concentrations, ionic clusters and we are currently working on resolving the long-standing problem of what determines their equilibrium size in terms of stable ordered structures. Molecular Walkers (Barrett) physical chemistry of materials The binding of macromolecules to surfaces is a key process in many nanotechnology applications. We have been examining how the degree of structural registry between a molecule and a crystal surface can dramatically alter both its binding energy and the mobility of the molecule. Using a very generic representation of molecular shape and rigidity, we are currently preparing a comprehensive mapping of the possible surface behaviour of molecules. Structure and Dynamics of Amorphous Alloys (Fernandez, Widmer-Cooper, Fynewever) The theoretical description of the properties of amorphous solids represents a major challenge in both materials science and the fundamental theory of condensed matter. Our tools are computer simulations of the dynamics of model liquids and the theoretical methods of statistical mechanics. We have introduced a fundamental new direction to this problem with the recognition that a meaningful structural description of the amorphous states is an essential prerequisite to a meaningful explanation of its dynamic behaviour. Our work has focussed on amorphous mixtures, models of the glassy alloys currently underdevelopment as advanced materials. In seeking to understand the structure of such mixtures, Fernandez and PH published a major study of the energetic of substitutionally ordered crystals comprising of binary mixtures of atoms. This study, along with providing a library of possible atomic structures and their associated energetics, offers a ready reference for designing model mixtures with desired crystal phases for studies of interfaces, phase transitions, etc. We also published a detailed study of the structure of a glassy alloy, modelled on the Ni-P system. In this work we identified a small set of coordination clusters that dominated the structure of the glass. We explored the relationship between these clusters, the structure of the glass and the stability with respect to crystallisation. This work has provided the starting point to our ongoing efforts to provide a general expression of glass and crystal structure in terms of combinations of generic structures. Turning to another major theme of our glass work, we (Widmer-Cooper, Fynewever and PH) published a new perspective on the phenomenon of dynamic heterogeneity in supercooled liquids. Addressing the persistent difficulty in finding a clear correlation between structure and these spatial variations in dynamics, we proposed that the propensity for motion rather than the actual motion itself was the more suitable quantity to link with structure. By establishing exactly what aspect of the dynamics is structurally determined we have provided a much clearer focus to the question of the structure-dynamics relationship. This work is currently being developed into a clear statement of the glass transition problem and the form the answer must take. Lubrication Films and the Statistical Theory of Friction (Petravic, Jabbarzadeh) Using a combination of nonequilibrium simulations and statistical theory of linear response, we are developing a comprehensive picture of the molecular level processes responsible for a remarkable range of rheology observed in thin films of lubricant between smooth crystalline walls. Studying nanometer thin films of dodecane between mica walls we (Jabbarzadeh, Tanner and PH) have established, in agreement with experiment, that both ultra-low friction films as well as practically rigid films can be produced depending on film thickness, wall structure and degree of film equilibration. The ultra-low friction films are associated with a state in which the linear alkane molecules are aligned while the very high friction state is the result of the formation of a novel ‘mosaic’ structure, quite distinct from anything observed in bulk crystals. We have also established that decreasing the in-plane order of the walls results in the destablization of both extremes of the rheological states. This latter result could provide valuable in designing surfaces for nanoscale fluidics. We (Petravic and PH) are also addressing the fundamental question of surface transport properties, thermal conductivity and friction, through the development of a new formulation of linear response theory aimed specifically at systems driven by boundary constraints. The general formalism is complete and was published in 200513 and we are working on using it to understand the molecular level contributions to these fundamental properties. Selected Publications 1. Harrowell, P. Glass transitions in plane view. Nature Physics, 2, 157-158, 2006. 2. Jabbarzadeh, A, Harrowell, P and Tanner, RI. Crystal bridge formation marks the transition to rigidity in a thin lubrication film. Physical Review Letters, 96, 206102, 2006. 3. Jabbarzadeh, A, Harrowell, P and Tanner, RI. Low friction lubrication between amorphous walls: Unraveling the contributions of surface roughness and in-plane disorder. Journal of Chemical Physics, 125, 034703, 2006. 4. Petravic, J and Harrowell, P. An equilibrium calculation of the thermal transport coefficients between two planes of arbitrary separation in a condensed phase. Journal of Chemical Physics, 124, 044512, 2006. 5. Petravic, J and Harrowell, P. Crystal-melt coexistence under shear: Interpreting the nonlinear rheology. Journal of Chemical Physics, 125, 124502, 2006. 6. Petravic, J and Harrowell, P. The boundary fluctuation theory of transport coefficients in the linear-response limit. Journal of Chemical Physics, 124, 014103, 2006. 7. Petravic, J and Harrowell, P. Erratum: Linear response theory for thermal conductivity and viscosity in terms of boundary fluctuations. Phys. Rev. E., 74, 049903, 2006. 8. Thomas, BS, Marks, NA and Harrowell, P. Inversion of defect interactions due to ordering in Sr1-3x/2LaxTiO3 perovskites: An atomistic simulation study. Physical Review B, 74, 214109, 2006. 9. Widmer-Cooper, A and Harrowell, P. Free volume cannot explain the spatial heterogeneity of Debye–Waller factors in a glassforming binary alloy. Journal of Non-crystalline Solids, 352, 5098-5102, 2006. 10. Widmer-Cooper, A and Harrowell, P. Predicting the long-time dynamic heterogeneity in a supercooled liquid on the basis of short-time heterogeneities. Physical Review Letters, 96, 185701, 2006. 11. Harrowell, P and Petravic, J. Linear response theory for thermal conductivity and viscosity in terms of boundary fluctuations. Physical Review E, 71, (6), 061201-1-061201-6, 2005. 12. Harrowell, P and Widmer-Cooper, A. On the relationship between structure and dynamics in a supercooled liquid. Journal of Physics Condensed Matter, 17, (49), 4025-4034, 2005. 13. Harrowell, P, Jabbarzadeh, A and Tanner, RI. Very low friction state of a dodecane film confined between mica surfaces. Physical Review Letters, 94, 126103-1-126103-4, 2005. 14. Widmer-Cooper, A, Fynewever, H and Harrowell, P. How reproducible are dynamic heterogeneities in a supercooled liquid? Phys. Rev.Lett., 93, 135701, 2004. 15. Wootton,A and Harrowell, P. Inorganic nanotubes stabilized by ion size asymmetry: Energy calculations for AgI clusters. J.Phys. Chem.B, 108, 8412, 2004. 16. Fernandez, J and Harrowell, P. Ordered binary crystal phases of Lennard-Jones mixtures. J.Chem.Phys., 120, 9222, 2004. 17. Fernandez, J and Harrowell, P. Organisation of coordination polyhedra in an amorphous alloy. J.Phys.Chem.B, 108, 6850, 2004. 18. Butler, S and Harrowell, P. Factors determining the crystal-liquid coexistence under shear. Nature, 415, 1008, 2002. 19. Wootton, A, Thomas, B and Harrowell, P. Radiation-induced densification in amorphous silica: A computer simulation study. J.Chem.Phys., 115, 3336, 2001. 20. Wild, R and Harrowell, P. Density functional theory of the kinetics of crystallization of hard-sphere suspensions. Coupling structure to density. J.Chem.Phys., 114, 9059, 2001. 44 School of Chemistry Dr Toby Hudson Room 209d School of Chemistry, F11 Telephone: +61 2 9351 4813 Facsimile: +61 2 9351 3329 Email: [email protected] http://www.chem.usyd.edu.au/~hudson_t Theoretical Materials Chemistry Annual Research Report 45 hopping Monte Carlo, attempt to solve this problem by exploring the vast configuration space efficiently. Fundamental to all of these methods are choices about: the way the system is represented; the mechanisms used for altering it; the ability to recognize recurring states that have already been tested; and the selection criteria for accepting a change. We developed a new, highly efficient method for recognizing states represented by discrete parameters [5]. In this vein we adapted genetic algorithms to use a discrete representation - the bond connectivity matrix - in atomic systems. We developed a robust procedure to map the system from bonds to Cartesian coordinates. However these genetic algorithms are not yet competitive in this system. This stems from the fact that when represented by their bonds, high valence networks are (redundantly) over-constrained. Thus when we try to “breed” pairs of different trial solutions, we get numerous clashing constraints, so the “child” is almost never a “viable” low-energy structure. We have also begun data mining the Inorganic Crystal Structure Database with the intention of extracting common structural motifs and trends for use in structural search. Initial results have found that two commonly occurring structures, when optimized, can pack binary hard spheres with a particular radius ratio even more densely than the close-packing the two species can obtain when separated. Only one example of this has previously been found amongst non-interstitial structures. Phase Field Models for Nucleation in Eutectic Binary Systems (Clements, Harrowell) The process of nucleation from the melt is a key determinant of the microstructure of a material, and its crystallization kinetics. This process is by its nature both small and fast, making it difficult to probe experimentally, but amenable to simulation. Simple analytic models are available for single-component systems if they are modelled with a single spatial parameter: crystallinity. However, in multi-component systems there is competition between nuclei of the different solids, as well as an intricate coordination between structural and compositional ordering. We constructed a phase-field model able to reproduce the essential features of a binary phase diagram with a eutectic point. This model was then solved for the case of a spherically-symmetric critical nucleus, allowing us to determine the compositional and structural radial profiles, together with the free energy of formation. This methodology can be applied to solidification at any temperature from any liquid composition, which allows us to overlay the phase diagram with measures of the predicted kinetics and microstructure upon a quench into these solid-solid coexistence regions. We are interested in applying a similar model to the equilibrium liquid state to investigate the nature of compositional and structural fluctuations. Amorphous Network Solids (Harrowell, Sutton†, Dwyer†, Winkelman†, Nguyen-Manh†, Cockayne†) In amorphous materials, computer modelling has the ability to probe atomic and topological information directly, whereas experiment often only gives averages and distributions. Nevertheless, this is vital to understanding their electronic and structural properties in applications such as photoelectric amorphous semiconductors. In contrast to crystals, where relaxation and diffusion mechanisms are dominated by the motion of individual, well-defined defects [4,5,8,9,10], amorphous materials often evolve using collective and unpredictable mechanisms. We developed a systematic series of topology-altering mechanisms, which can be applied to any network, and conserve the valence of every atom [1]. The series includes concerted mechanisms involving multiple bond rearrangements. It can be used to categorize observed topological changes, or as a broad set of trial moves that can be used in Monte Carlo simulations of these materials. These mechanisms were tested in separate MC simulations on a simple tetravalent continuous random network, allowing us to establish their efficiency for both energetic minimization, and structural sampling [1]. On both measures, we showed that a previously known and widely used mechanism is indeed optimal at low temperatures, and found other good candidates for use in combination with it, or for use at higher temperatures. Structural Search Algorithms (Kummerfeld, Harrowell, Mason†) In condensed matter systems there are an extremely large number of metastable local energy minima, which confound easy discovery of the true global minimum. This problem strikes a number of fields, including cluster chemistry, protein folding, and complex crystals. Stochastic search algorithms such as simulated annealing, genetic algorithms, and basin Global energy minimum structures of Lennard-Jones clusters LJ-55, LJ-81, and LJ-150, obtained from a representation in which only the bond connectivity matrix was provided. † Co-worker not associated with the University of Sydney. Selected Publications 1. Hudson, TS and Harrowell, P. A systematic enumeration of local topological relaxation mechanisms in amorphous networks and their efficiency in network relaxation. Journal of Chemical Physics, 126, 184502, 2007. 2. Hudson, TS, Nguyen-Manh, D, van Duin, ACT and Sutton, AP. Grand canonical Monte Carlo simulations of intergranular glassy films in b silicon nitride. Materials Science and Engineering A-Structural Materials Properties Microstructure and Processing, 422, 123-135, 2006. 3. Winkelman, GB, Dwyer, C, Marsh, C, Hudson, TS, Nguyen-Manh, D, Doblinger, M and Cockayne, DJH. The crystal/glass interface in doped Si3N4. Materials Science & Engineering, A: Structural Materials: Properties, Microstructure and Processing, A422 (1-2), 77-84, 2006. 4. Hudson, TS, Caturla, M-J, Dudarev, SL and Sutton, AP. Effects of elastic interactions on post-cascade radiation damage evolution in kinetic Monte-Carlo simulations. Philosophical Magazine, 85, 661-675, 2005. 5. Mason, DR, Hudson, TS and Sutton, AP. Fast recall of state-history in kinetic Monte-Carlo simulations utilising the Zobrist key. Computer Physics Communications, 165, 37-48, 2005. 6. Winkelman, GB, Dwyer, C, Hudson, TS, Nguyen-Manh, D, Doblinger, M, Satet, RL, Hoffmann, MJ and Cockayne, DJH. Three dimensional organization of rare-earth atoms at grain boundaries in silicon nitride. Applied Physics Letters, 87, 1-3, 2005. 7. Winkelman, GB, Dwyer, C, Hudson, TS, Nguyen-Manh, D, Doeblinger, M, Satet, RL, Hoffmann MJ and Cockayne, DJH. Arrangement of rare-earth elements at prismatic grain boundaries in silicon nitride. Philosophical Magazine Letters, 85, 755-762, 2004. 8. Hudson, TS, Dudarev, SL and Sutton, AP. Suppression of interstitial cluster diffusion by oversized solute atoms. Journal of Nuclear Materials, 329-333, 971-976, 2004. 9. Hudson, TS, Dudarev, SL and Sutton, AP. Confinement of interstitial cluster diffusion by oversized solute atoms. Proceedings of the Royal Society of London: Math. Phys. & Eng. Sci., 460, 2457-2475, 2004. 10. Hudson, TS, Dudarev, SL and Sutton, AP. Absence of saturation of void swelling in rate theory with anisotropic diffusion. Journal of Nuclear Materials, 307-311, 976-981, 2002. 46 School of Chemistry Annual Research Report Dr Julia M James Analytical & Environmental Geochemistry Our research interests are in the area of environmental geochemistry with special emphasis on the chemical reactions taking place in caves. Some studies in progress are: Paleoclimatic Studies From Speleothems And Cave Sediments We are obtaining paleoclimatic records from speleothems and sediments throughout Australia using uranium/thorium radionuclide methods. The average temperatures at the time of deposition are established by stable isotope measurements. Submerged calcite deposits found under the Nullarbor Plain are being studied for their association with bacterial colonies and the variation in surface temperature and sea level changes over the last 4 million years. These results are important in modelling future changes in sea-level from the greenhouse effect. Trace Organics And Trace Metals In Speleothems Studies Extraction and identification of trace metals and organic materials and their complexes from within the calcite matrix are being carried out. We have established that amino acids are present in many speleothems and are using amino acid racemisation dating techniques to study the geochemical record of specimens up to one million years old. Selected Publications 1. James, JM. Corrosion par melange des eaux dans les grottes de la plaine de Nullarbor, Australie (Mixing corrosion in the caves of the Nullarbor Plain, Australia). Special issue of Karstologia, Karst et Evolutions Climatics, 332-347, 1992. 2. Contos, AK, James, JM, Heywood, B, Pitt, K and Rogers, P. Morphoanalysis of bacterially precipitated subaqueous calcium carbonate from Weebubbie Cave, Australia. Geomicrobiology, 18, 331-343, 2001, 3. Holmes, AJ, Tujula, NA, Holley, NM, Contos, AK, James, JM and Rogers, PAW. Phylogenetic structure of unusual aquatic microbial formations in the Nullarbor Caves, Australia. Environmental Microbiology, 3, (4), 256-264, 2001. 4. Hose, GC, James, JM and Gray, MR. Spiders webs as environmental indicators. Environmental Pollution, 725-733, 2002. 5. James, JM. The crystal gallery. In Beneath the Surface: A Natural History of Australian Caves, edited by Finlayson, B and HamiltonSmith, E, University of NSW Press, 53-86, 2003. 6. James, JM, Contos, AK and Barnes, C. The Nullarbor Caves. In Encyclopaedia of Caves, edited by David Culver, and William White, WB, New York, Elsevier, 418-426, 2004.7. 7. James, JM. Giant dolines of the Muller Plateau, Papua New Guinea. Cave and Karst Science, 32, 85-91, 2005. 8. Webb, JA and James, JM. Karst evolution of the Nullarbor Plain, Australia, in Harmon, R.S., and Wicks, C., eds. Perspectives on karst geomorphology, hydrology, and geochemistry — A tribute volume to Derek C. Ford and William B. White: Geological Society of America Special Paper 404, 65–78, 2006. Diver sampling rare calcite precipitating microbial mantles in the Weebubbie Lake Honorary Staff Room 146 School of Chemistry, F11 Telephone: +61 2 9351 2743 Facsimile: +61 2 9351 3329 Email: [email protected] http://www.chem.usyd.edu.au/about/staff_james.html 47 48 School of Chemistry Dr Katrina A Jolliffe Room 515 School of Chemistry, F11 Telephone: +61 2 9351 2297 Facsimile: +61 2 9351 3329 Email: [email protected] http://www.chem.usyd.edu.au/about/staff_jolliffe.html Annual Research Report 49 useful is to get enough 10B to the tumour cells. Cyclic RGD peptides are capable of specifically targeting integrin proteins which are overexpressed by tumour cells. We are investigating the attachment of 10B-containing agents to these tumour targeting peptides to enable the selective delivery of 10B to multiple tumour types for BNCT. Cyclic Peptide Based Anion Receptors (Reynolds, McDonough, Young, Butler) The selective recognition and sensing of biologically important anions under physiological conditions is of intense current interest to both chemists and biologists, since this has numerous applications in biomedicine. Backbone modified cyclic peptides are ideal scaffolds for the construction of molecular anion receptors and we are currently investigating the synthesis and application of a range of such receptors. Anions such as pyrophosphate (P2O74-, PPi) play important roles in bioenergetic and metabolic processes. We have recently developed a cyclic-peptide based fluorogenic ‘chemosensing ensemble’ capable of selectively detecting low concentrations of PPi under physiological conditions. Organic Synthesis and supramolecular chemistry New Methods for the Efficient Cyclisation of Small Peptides (Sayyadi, Leesch, Cochrane) There has recently been a great deal of interest in the synthesis of small cyclic peptides. Naturally occurring cyclic peptides exhibit a wide range of biological activities and are often more resistant to enzymatic hydrolysis than their linear counterparts. Additionally, the restricted conformational flexibility of cyclic peptides allows them to present functional groups in a spatially well-defined manner and is of use in the study and mimicry of protein folding. However, the currently available methods for the head-to-tail cyclisation of linear peptides are often slow and low-yielding. We recently developed a new method for the efficient head-to-tail synthesis of small cyclic peptides and examined its use in a model system. We have now extended this methodology to the synthesis of novel cyclic peptides incorporating from 4-9 amino acids and have applied it in the synthesis of the anti-malarial cyclic peptide mahafacyclin B, increasing the cyclisation yield from 23% to over 60%. Other cyclic peptide targets including Axinellin A, a cyclic peptide with antitumour activity, and LIF-04a, a cyclic depsipeptide with antifungal activity, are currently being synthesised. Design and Synthesis of Selective Inhibitors of Fungal Virulence Factors (Obando, Sorrell*, Widmer*) Pathogenic fungi are increasingly implicated as a cause of serious and potentially fatal disease, especially in immunocompromised hosts. Many of these fungi have been found to secrete enzymes that contribute to their virulence and therefore present new targets for drug discovery. The primary aim of this project is to design and synthesise selective inhibitors of fungal phospholipases for use as therapeutic agents. We are examining a number of compound classes for antifungal and phospholipase inhibitory activity and have found that these are correlated, supporting the hypothesis that the fungal phospholipase is a new target for drug discovery. We have synthesised a number of compounds that show strong inhibition of the fungal enzyme but do not inhibit mammalian phospholipases and our best compound has comparable antifungal activity to the currently marketed antifungal drug, Amphotericin B. Boronated Cyclic Peptides for Cancer Treatment Using BNCT – (Rendina, Ziolkowski) Boron Neutron Capture Therapy (BNCT) is a new cancer treatment that relies on the remarkable neutron capture properties of the non-radioactive 10B nucleus. The major problem that needs to be overcome for BNCT to be clinically Self-Assembled Molecular Capsules (Yuen, O’Malley, Clegg, Lindoy) Backbone rigidified cyclic peptides are ideal platforms for use in the preparation of nanoscale molecular capsules, as they allow the functional groups required for self-assembly to be arranged in a spatially well-defined manner and will provide capsules with a large interior volume. We are investigating the use of azole-heterocycle containing cyclic peptides for this purpose and have prepared a number of scaffolds, functionalised with ligands, for self assembly upon the addition of an appropriate metal ion. Selected Publications 1. Ng, CKL, Singhal, V, Widmer, F, Wright, LC, Sorrell, TC and Jolliffe, KA. Synthesis, antifungal and hemolytic activity of a series of Bis(pyridinium)alkanes. Bioorg. Med. Chem., 15, 3422-3429, 2007. 2. McDonough, MJ, Reynolds, AJ, Lee, WYG and Jolliffe, KA. Selective recognition of pyrophosphate in water using a backbone modified cyclic peptide receptor. Chem Commun., 2971-2973, 2006. 3. Di Vittorio, KM, Johnson, JR, Johansson, E, Reynolds, AJ, Jolliffe, KA and Smith, BD. Synthetic peptides with selective affinity for apoptotic cells. Org. Biomol. Chem., 4, 1966-1976, 2006. 4. Ng, CKL, Obando, D, Widmer, F, Wright, L, Sorrell, TC and Jolliffe, KA. Correlation of antifungal activity with fungal phospholipase inhibition using a series of bisquaternary ammonium salts. J. Med. Chem., 49, 811-816, 2006. 5. Sayyadi, N, Skropeta, D and Jolliffe, KA. N,O-isopropylidenated threonines as tools for peptide cyclisation: Application to the total synthesis of mahafacyclin. Org. Lett., 7, 5497-5499, 2005. 6. Jolliffe, KA. Backbone modified cyclic peptides: New scaffolds for supramolecular chemistry. Supramol. Chem., 17, 81-86, 2005. 7. Skropeta, D, Jolliffe, KA and Turner, P. Pseudo-prolines as removable turn inducers: Tools for the cyclisation of small peptides. J. Org. Chem., 69, 8804-8809, 2004. 50 School of Chemistry Dr Meredith Jordan Room 241 School of Chemistry, F11 Telephone: +61 2 9351 4420 Facsimile: +61 2 9351 3329 Email: [email protected] http://www.chem.usyd.edu.au/about/staff_jordan.html 51 Annual Research Report Molecular Structure (Chebib,1 Crittenden, Thompson) We have combined the Grow package with quantum diffusion Monte Carlo methods to allow us to accurately predict the vibrationally averaged (ground state) structure of relatively large molecules and clusters. We have applied these methods to ethanediol. H2O, glycine.8H2O, glycyl radical.8H2O and GABA.5H2O. We have also developed the first chemically accurate PES for the CH5+ system, chemistry’s “cheshire cat”. Representations of some of our molecular structures are illustrated: intermolecular interactions Computational Drug Design (Chebib,1 Crittenden) γ-aminobutyric acid (GABA) is the major neuro-inhibitor in the brain. Understanding how GABA works aids in developing drugs to treat diseases such as epilepsy, depression, anxiety and Alzheimer’s disease. We have developed new computational techniques to study in vivo amino acids and have applied these, together with experiment, to GABA and a range of GABA analogues. This has enabled us to determine the first Quantitative Structure Activity Relationship (QSAR) for the GABAC receptor and to characterize the bioactive template molecule, TACA. below-plane substitution here tolerated, may possess either agonist or antagonist activity all above-plane substitution tolerated, with agonist activity below-plane substitution here strictly not tolerated GABA.5H2O The most probably structure of CH5+ Molecular Reactivity (Crittenden, Kable, Thompson) We have calculated the first accurate PES for the photodissociation of T1 acetaldehyde, a reaction important in atmospheric pollution. Dynamical calculations on this PES agree well with experiment and provide the first theoretical demonstration of reaction dynamics undergoing a transition from impulsive to statistical behaviour in the product state distributions as excess energy increases. Our calculations have also resolved a number of discrepancies in previous experimental and theoretical studies of this system. Faculty of Pharmacy, University of Sydney Faculty of Medicine, University of Sydney 3 School of Molecular and Microbial Biosciences, University of Sydney 1 2 The Calcium Sensing Receptor (CaSR) (Clifton-Bligh,2 Conigrave,3 Corley) The CaSR is involved in regulating calcium within the body and is a target for drugs to treat osteoporosis, one of the major health issues facing Australia. We have modelled the interaction of hydrated Ca2+, Mg2+ and Sr2+ ions with the amino acid residues implicated in the CaSR showing the importance of acidic and very polar residues together with the protein backbone group. We have used these models to describe the qualitative and quantitative differences observed between the binding of the Ca2+ and Mg2+ ions. Our calculations have enabled us to identify a putative binding site within the extracellular domain of the CaSR. Putative CaSR binding site: S147, S170, S171, D190, Y218, G273, S296, E297 Potential binding pocket for cation Molecular Potential Energy Surfaces (Collins,* Thompson, Crittenden) Molecular potential energy surfaces (PES) describe how the energy of a molecule changes as the positions of its constituent atoms change. We have developed new interpolation techniques for constructing PES based on highly accurate quantum chemical calculations. A new computer package Grow has been released making these techniques freely available and we are currently implementing Grow within the GAMESS quantum chemical program suite. Selected Publications 1. Crittenden, DL, Park, A, Qiu, J, Silverman, RB, Duke, RK, Johnston, GAR, Jordan, MJT and Chebib, M. Enantiomers of cisconstrained and flexible 2-substituted GABA analogues exert opposite effects at recombinant GABAC receptors. Bioorganic & Medicinal Chemistry, 14, 447-455, 2006. 2. Thompson, K, Crittenden, DL, Kable, SH and Jordan, MJ. A classical trajectory study of the photodissociation of T1 acetaldehyde: The transition from impulsive to statistical dynamics. Journal of Chemical Physics, 124, 044302, 2006. 3. Crittenden, DL, Chebib, M and Jordan, MJT. Quantitative structure-activity relationships of GABAC receptor agonists. J. Mol. Struct., (Theochem), 755, 81-89, 2005. 4. Crittenden, DL, Kumar, RJ, Hanrahan, J, Chebib, M and Jordan, MJT. The stabilisation of zwitterions in solution: Phosphonic and phosphinic acid GABA analogues. J. Phys. Chem. A, 109, 8398-8409, 2005. 5. Crittenden, DL, Chebib, M and Jordan, MJT. The stabilisation of zwitterions in solution: GABA analogues. J. Phys. Chem. A, 109, 4195-4201, 2005. 6. Thompson, KC, Crittenden, DL and Jordan, MJT. CH5+: Chemistry’s chameleon unmasked. J. Am. Chem. Soc., 127, 4954-4958, 2005. 7. Crittenden, DL, Thompson, KC and Jordan, MJT. On the extent of intramolecular hydrogen bonding in gas-phase and hydrated 1,2-ethanediol. J. Phys. Chem. A, 109, 2971-2977, 2005. 8. Crittenden, DL and Jordan, MJT. Interpolated potential energy surfaces: How accurate do the second derivatives have to be? J. Chem. Phys., 122, 044102, 2005. 52 School of Chemistry Associate Professor Scott H Kable Room 308 School of Chemistry, F11 Telephone: +61 2 9351 2756/3811 Facsimile: +61 2 9351 3329 Email: [email protected] http://www.chem.usyd.edu.au/about/staff_kable.htm laser-induced chemistry Lasers have revolutionised many aspects of chemistry, including our understanding of chemical reactivity, characterisation of new materials, and all forms of spectroscopy. The reason for this large diversity of applications lies in the range of effects that intense light has on different materials – breaking bonds, ablating solids, ionising materials, and tickling molecules to behave in certain ways. The research interests of our group include photochemistry, spectroscopy, mass spectrometry and theoretical chemistry. More details can be found on our web page. Photodissociation Dynamics (Jordan, Rowling, Heazlewood) Chemical reactions are often understood in terms of a specific reaction mechanism or pathway. When two or more competing mechanisms give rise to the same chemical products, then our ability to predict rates, branching ratios, and quantum yields is compromised. It is experimentally and theoretically challenging to separate the influence of each competing pathway to reveal the underlying mechanisms. The photodissociation of H2CO is crucial in the chemistry of the atmosphere, and exhibits two such competing mechanisms. The production of H + HCO is an example of a reaction occurring on two different electronic states, which compete in the production of a single set of products. The ground state (S0) is barrierless, whereas the lowest triplet state (T1) has a small barrier. In 2005, in collaboration with researchers from Emory University, we identified the fingerprints of these mechanisms (Science, 2006, 311, 1443), and recently published a full description of the process (J. Chem. Phys, 2007, in press). Reactions on S0 produce HCO with high rotational excitation (N in figure), and are modelled well by statistical theory of photodissociation. The T1 channel produces HCO that is rotationally cold. High level trajectory calculations confirm the identification and quantitatively reproduce the experimental data. We also examined the photodissociation dynamics of acetaldehyde and discovered that acetaldehyde reacts to form the molecular products CO + CH4 via two different mechanisms. One of these is the traditional “transition state mechanism” (see right), in which the reaction proceeds via a well-defined 3-centre transition state. The other proposed mechanism is via a “roaming”-type pathway, which was first demonstrated by Suits and Bowman in the case of formaldehyde. In the roaming mechanism, the reaction proceeds towards radical products, HCO + CH3 , however, doesn’t quite make it. The methyl group then roams around the periphery of the HCO core, then re-reacts with itself, Annual Research Report 53 abstracting a H-atom from HCO and ends up as extremely hot methane and very cold CO. If proven, then this is only the second example of roaming in the literature, and the first example of a anything except a H-atom roaming. Spectroscopy and Structure of Radicals (Bacskay, Schmidt, Reilly) Free radicals have proven elusive to study because of their inherence reactivity. Consequently, the chemistry and structure of many radicals remains unknown and has been the subject of active research for many years. In collaboration with Dr Schmidt in the School of Chemistry, we have turned our attention to radical species that might be found in the interstellar medium. Many UV-visible absorption and emission bands around and between stars appear to exhibit molecular fingerprints, yet the majority have not been identified. There are almost as many theories as observations, but the only way to positively identify these bands is by measuring them in the laboratory (see Dr Schmidt’s page for more details about the astro-spectroscopy project). In 2005, we installed and tested a new discharge nozzle and in 2006 we generated new spectra of important molecules and discovered new molecules. Dicarbon (C2) is a textbook example of chemical bonding, alongside N2 and O2. Last year we reported a new spectroscopic transition and measured a new electronic state of C2 (C2 is of such importance that transitions are usually named after the discoverers.) This is the only known transition involving this state, and will be crucial for astronomical models of carbon abundance in space. We have also very recently discovered a new molecule, the phenylpropargyl radical, that is formed in a benzene discharge. Most intriguingly, this molecule absorbs light at 476 nm, which corresponds to one of the mysterious, unassigned diffuse interstellar bands that have been taunting astronomers since their discovery 80 years ago. 2-Dimensional Fluorescence Spectroscopy (Schmidt, Reilly) The “soup” of unstable and reactive species formed in the discharge is very rich, and so too is the spectroscopy complicated by overlapping bands. We have developed a two-dimensional spectroscopic technique that we use to untangle the many spectral features and verify spectral bands that belong to the same carrier. This technique was published in J. Phys. Chem. A and featured on the front cover (right). The technique allows intuitive association of spectra features that belong to the same carrier, and also allows the complete separation of two completely overlapping transitions in the excitation spectrum , providing the emission signatures are different. This technique was indispensable in the discovery of the new C2 bands and the discovery of the phenylpropargyl radical described above. Selected Publications 1. Kokkin, DL, Reilly, NJ, Morris, CW, Nakajima, M, Nauta, K, Kable, SH and Schmidt, TW. Observation of the d3pg – c3Su band system of C2. Journal of Chemical Physics, 125, 231101, 2006. 2. Reilly, NJ, Schmidt, TW and Kable, SH. Two-dimensional fluorescence (excitation/emission) spectroscopy as a probe of complex chemical environments. Journal of Physical Chemistry A, 110, 12355-12359, 2006. 3. Houston, PL and Kable, SH. Photodissociation of acetaldehyde as a second example of the roaming mechanism. Proceedings of the National Academy of Sciences of the United States of America, 103, 16079-16082, 2006. ~ ~ 4. Yin, H-M and Kable, SH. Rotational analysis of the HCO B(2A´ ) – X(2A´ )311 and 312 bands. Journal of Molecular Spectroscopy, 237, 163-173, 2006. 5. Reilly, NJ, Cupitt, GC, Kable, SH and Schmidt, TW. An experimental and theoretical investigation of the dispersed fluorescence spectroscopy of HC4S. Journal of Chemical Physics, 124, 194310, 2006. 6. Yin, HM, Kable, SH, Zhang, X and Bowman, JM. Signatures of H2CO photodissociation from two electronic states. Science, 311, 1443-1446, 2006. 7. Zhu, H, Zheng, Z, Gao, X, Huang, Y, Yan, Z, Zou, J, Yin, H, Zou, Q, Kable, SH, Zhao, J, Xi, Y, Martens, WN and Frost, RL. Structural evolution in a hydrothermal reaction between Nb2O5 and NaOH solution: From Nb2O5 grains to microporous Na2Nb2O6 • 2/3H2O fibers and NaNbO3 cubes. Journal of the American Chemical Society, 128, 2373-2384, 2006. 8. Sharp, RG, Reilly, NJ, Kable, SH and Schmidt, TW. Sequence structure emission in the red rectangle bands. Astrophysical Journal, 639, 194-203, 2006. 9. Thompson, K, Crittenden, DL, Kable, SH and Jordan, MJ. A classical trajectory study of the photodissociation of T1 acetaldehyde: The transition from impulsive to statistical dynamics. Journal of Chemical Physics, 124, 044302, 2006. 54 School of Chemistry Associate Professor Brendan J Kennedy Room 458 School of Chemistry, F11 Telephone: +61 2 9351 2742 Facsimile: +61 2 9351 3329 Email: [email protected] http://www.chem.usyd.edu.au/about/staff_kennedy.html solid state and materials chemistry Perovskite-type oxides are the most widely used ceramics for technological applications as a consequence of the rich variety of physical properties they display that arise as a result of structural phase transitions. Much of our research is associated with understanding the origins of structural phase transitions and the complex interplay between structure and physical properties. Phase Transitions in Perovskite Oxides (Macquart, Zhou, Cheah, Howard1) The majority of experimental studies conducted over the past year have been directed towards providing experimental support for the group theoretical study of phase transitions in ordered double perovskites that was published in 2003 (Acta Cryst 2003 B59, 463-471). Extensive studies were completed on the series of oxides A2NiWO6, where A is an alkaline earth cation. The structures of the 27 oxides of this type have been determined using synchrotron X-ray powder diffraction methods, with additional neutron patterns being collected for a smaller number of samples. These studies demonstrated =1.430 =1.480  → I 4 / m r  → Fm 3 m . the symmetry increases as the average size of the A-site cation, rA increases as follows P 21 / n r Interest has also centered on the oxides A2LnMO6 where Ln is Pr or Tb and M is Ir or Ru. These oxides exhibit unusual valence transitions associated with the rare earth cation (Tb or Pr) that can be induced by chemical substitution, or by changes in temperature or pressure. In addition to these studies of double perovskites we have completed a detailed analysis of the phase transition behaviour in PrAlO3. This oxide is extremely unusual in that the Jahn-Tellar distortion associated with the PrIII cation has the same symmetry as the in-phase tilting of the AlO6 octahedra. Structural and lattice parameter data have then been used to follow details of octahedral tilting and spontaneous strains associated with the sequence of phase transitions Pm 3 m ↔ R3 c ↔ Imma ↔ C2/m. These are interpreted in terms of strain/order parameter coupling using a single Landau free energy expansion for a Pm 3m reference structure with two instabilities ( r+4 and G+3 active). The Pm 3 m ↔ R3 c transition appears to be second order in character with an extrapolated transition temperature of 1864 ± 31 K. The R3 c ↔ Imma transition is first order in character and can be understood as occurring because coupling takes place between tilting and electronic order parameter components via a common tetragonal strain. Strains for the Imma ↔ C2/m transition conform closely to the Landau solution for a proper ferroelastic transition with second order character and low temperature saturation. a a Structure and Properties of Bismuth Containing Oxides (Macquart, Zhou) Our studies in this area have been focused on understanding the ferroelectric to paraelectric phase transition in layered Aurivillius-type oxides such as SrBi2Nb2O9 is reported. Using a combination of high resolution diffraction studies and group theory we have shown that SrBi2Nb2O9 transforms from the polar orthorhombic structure in space group A21am to the high temperature paraelectric tetragonal structure (I4/mmm) via an intermediate orthorhombic phase in Amam. A number of other oxides have also been studies and recent work has been directed towards the preparation of novel layered Bi oxides that incorporate a paramagnetic ion. Annual Research Report 55 Neutron and X-Ray Studies of Materials (Saines, Arora, Howard) The rapid development in high-resolution instruments at advanced neutron and synchrotron facilities has opened up numerous new fields of chemistry. Two projects that have relied on such advances include the study of long life phosphors based on lanthanide doped aluminates of the type AAl2O4. Structural studies of these oxides suggest the reason for the limited solubility of rare earth cations in these oxides. The second area has been in the study of the up-take of heavy metals, in particular lead, by apatite type minerals. Micro SRIXE measurements have been used to study the incorporation of lead into teeth during the early stages of their development. These studies suggest an alternate strategy in monitoring exposure of infants to heavy metals. 1 ANSTO Selected Publications 1. Arora, M, Kennedy, BJ, Elhlou, S, Pearson, NJ, Walker, DM, Bayl, P and Chan, SWY. Spatial distribution of lead in human primary teeth as a biomarker of pre- and neonatal lead exposure. Science of the Total Environment, 371, 55-62, 2006. 2. Cheah, M, Saines, PJ and Kennedy, BJ. The Jahn–Teller distortion and cation ordering in the perovskite Sr2MnSbO6. Journal of Solid State Chemistry, 179, 1775-1781, 2006. 3. Cheah, MCL, Kennedy, BJ, Withers, RL, Yonemura, M and Kamiyama, T. Synthesis, structures and phase transitions in the double perovskites Sr2-xCaxCrNbO6. Journal of Solid State Chemistry, 179, 2487-2494, 2006. 4. Kennedy, BJ, Howard, CJ, Knight, KS, Zhang, Z and Zhou, Q. Structures and phase transitions in the ordered double perovskites Ba2BiIIIBiVO6 and Ba2BiIIISbVO6. Acta Crystallographica Section B-Structural Science, 62, 537-546, 2006. 5. Lian, J, Helean, KB, Kennedy, BJ, Wang, LM, Navrotsky, A and Ewing, RC. Effect of structure and thermodynamic stability on the response of lanthanide stannate-pyrochlores to ion beam irradiation. Journal of Physical Chemistry B, 110, 2343-2350, 2006. 6. Saines, PJ and Kennedy, BJ. Implications of the solubility of trivalent lanthanides in AAI2O4 (A=Ca, Sr, and Ba) for their role in phosphors. Powder Diffraction, 21, 285-288, 2006. 7. Saines, PJ, Elcombe, MM and Kennedy, BJ. Lanthanide distribution in some doped alkaline earth aluminates and gallates. Journal of Solid State Chemistry, 179, 613-622, 2006. 8. Saines, PJ, Elcome, MM and Kennedy, BJ. Structural studies of oxygen deficient lanthanide containing double perovskites. Physica B, 385-386, 187-189, 2006. 9. Somphon, W, Ting, V, Liu, Y, Withers, RL, Zhou, Q and Kennedy, BJ. Local crystal chemistry, structured diffuse scattering and the dielectric properties of (Bi1-xYx)2(MIIINbV)O7 (M=Fe3+, In3+) Bi-pyrochlores. Journal of Solid State Chemistry, 179, 24952505, 2006. 10. Zhou, Q and Kennedy, BJ. Thermal expansion and structure of orthorhombic CaMnO3. Journal of Physics and Chemistry of Solids, 67, 1595-1598, 2006. 11. Zhou, Q, Kennedy, BJ and Elcombe, MM. Neutron powder diffraction studies of Ca2-xSrxCoWO6 double perovskites. Physica B, 385-386, 190-192, 2006. 12. Zhou, Q, Kennedy, BJ and Elcombe, MM. Synthesis and structural studies of cation-substituted Aurivillius phases ASrBi2Nb2TiO12. Journal of Solid State Chemistry, 179, 3744-3750, 2006. 56 School of Chemistry Professor Cameron J Kepert Room 456 School of Chemistry, F11 Telephone: +61 2 9351 5741 Facsimile: +61 2 9351 3329 Email: [email protected] http://www.chem.usyd.edu.au/about/staff_kepert.html molecular framework materials Nanoporous Molecular Frameworks (Southon, Yuan, Duyker, Phillips, Weeks, Halder, Bevitt, Chapman, Faiz, Kolibac) A range of new framework materials that display reversible guest sorption is being investigated.2 Characterisation of the dynamic host-guest structures of these phases was explored using two new experimental techniques developed in our lab, the first involving the in-situ measurement of single crystal X-ray diffraction data during gas and vapour sorption/ desorption1,4,6,7,8,11,13 and the second involving the measurement of diffuse X-ray scattering to provide differential pair distribution functions (PDFs).10 Following our design and construction of purpose-built capillary flow cells, the uptake of a number of small molecular sorptives into a range of different nanoporous phases has been explored. Gas and vapour sorption measurements and in-situ powder X-ray diffraction investigations have further enhanced our kinetic, thermodynamic and structural understandings of the sorption chemistry of these phases. Hydrogen Storage (Peterson, Southon, Iremonger, Weeks, Chapman, Bevitt, Kolibac) The safe and efficient storage of hydrogen gas represents a pivotal challenge in the development of hydrogen as an alternative energy carrier. Our recent report of a system in which dihydrogen molecules bind directly to bare metal sites within a nanoporous molecular framework material (see picture)3 has provided an important new advance in this area and points the way to hybrid materials in which hydrogen gas can be loaded and released under non-extreme conditions of temperature and pressure. A systematic structural characterisation of progressive hydrogen loading provided a uniquely detailed understanding of the mechanism of pore filling. We are extending this interest to other systems that may display this novel property. Continuing investigations of hydrogen sorption in Prussian Blue phases12 has seen fully reversible dihydrogen uptakes approaching 2 wt%. Switching Nanoporous Materials (Halder, Amoore, Sciortino, Robertson, Liu, Neville, Iremonger, Hudson, Murray, Moubaraki, Toftlund, Letard, Guionneau) Our incorporation of molecular electronic switches into nanoporous frameworks1 and dinuclear complexes4 is leading to materials and molecules that have unique physicochemical properties and potential applications in molecular sensing and data storage. Through the systematic variation of the bridging ligand and counter-ion we have developed an extensive family of materials of this type, allowing fine-tuning of guest-exchange (pore size and shape) and switching (transition temperature) properties. Of particular note is the recent synthesis and characterisation of the first dinuclear spin crossover complex to be exhibit a full two-step crossover (see figure). Variation of included guest molecules perturbs the crossover properties of this complex, converting it from two-step to single-step. Measurements performed in Bordeaux have demonstrated that a number of our phases may be switched under laser irradiation at low temperature (the LIESST effect). Annual Research Report 57 Porous Magnetic Frameworks (Shigematsu, Neville, Chapman, Kurmoo) As an extension of our efforts to incorporate electronic and magnetic function into nanoporous molecular frameworks we are designing and synthesising porous materials that display magnetic ordering. Guest-exchange in such materials may be used to perturb the magnetic properties, thereby providing a unique technique for investigating magnetic structureproperty relationships. Of particular note in this area is our recent discovery of a highly robust nanoporous phase that converts from an antiferromagnet to a ferromagnet with the reversible removal of unbound water molecules.13 Negative Thermal Expansion (Duyker, Phillips, Kobayashi, Yuan, Chapman, Goodwin, Pretsch, Kennedy, Withers, Dove, Hagen, Hester, Knight) Investigations of the anomalous thermal expansion behaviour of metal cyanide frameworks have uncovered a wealth of novel properties.5,6,8,9 We attribute the unprecedented negative thermal expansion (NTE) in these systems to two different modes of transverse vibrational motion of the linear cyanide bridge, each one leading to a decrease in the M…M distance with increasing temperature. Characterisations have been performed at ISIS, Harwell, UK, the Australian National Beamline Facility, Tsukuba, Japan, and the Advanced Photon Source, Chicago, USA. Data from the latter has led to the characterisation of metal-5,6 and guest-8 dependent NTE in these phases, and to the first PDF analysis of an NTE material.9 Investigations of single diamondoid network phases, which includes both neutral and anionic network phases, has led to detailed understandings of the influence of the guest volume and charge on NTE. Systematic characterisation of lanthanoid-containing NTE phases have allowed us to decorrelate the influence of metal-cyanide bond energy and ionic radius on NTE properties. Porous Mineral Formulations (Yuan, Antill, Green, Matthews, Anderson, Wells) In this project we are collaborating with an industrial partner on the generation of new technologies for the controlled release delivery of agrochemicals from porous mineral phases. Recent progress has seen the successful control of release properties through the modification of surface chemistry. In parallel with this project we are using halloysite nanotubes (geometric analogues of the more expensive carbon or boron nitride nanotubes) as templates for fabrication of nanostructures such as nanowires, rods and clusters. Selected Publications 1. Neville, SM, Moubaraki, B, Murray, KS and Kepert, CJ. A thermal spin transition in a nanoporous iron(II) coordination framework material. Angew. Chem. Int. Ed., 46, 2059-2062, 2007. 2. Kepert, CJ. Advanced functional properties in nanoporous coordination framework materials. Chem. Commun., 695-700, 2006. 40th Anniversary Focus Article. 3. Peterson, VK, Liu, Y, Brown, CM and Kepert, CJ. Neutron powder diffraction study of D2 sorption in Cu3(1,3,5-benzenetricarboxylate)2. J. Am. Chem. Soc., 128, 15578-15579, 2006. Highlighted in C&EN: see http://pubs.acs.org/cen/news/85/i01/8501notw8.html. 4. Amoore, JJM, Kepert, CJ, Moubaraki, B, Murray, KS and Neville, SM. Structural and magnetic resolution of a two-step spincrossover transition in a dinuclear iron(II) pyridyl-bridged compound. Chem. Eur. J., 12, 8220-8227, 2006. VIP Article with cover picture. 5. Chapman, KW, Chupas, PJ and Kepert, CJ. Compositional dependence of negative thermal expansion in the Prussian Blue analogues MIIPtIV(CN)6 (M = Mn-Zn, Cd). J. Am. Chem. Soc., 128, 7009-7014, 2006. 6. Pretsch, T, Chapman, KW, Halder, GJ and Kepert, CJ. Dehydration of the nanoporous coordination framework ErIII[CoIII(CN)6]∙ 4(H2O): Single crystal to single crystal transformation and negative thermal expansion in ErIII[CoIII(CN)6]. Chem. Commun., 18571859, 2006. 7. G.J. Halder, C.J. Kepert, “Single-crystal-to-single-crystal structural transformations in molecular framework materials”, Aust. J. Chem., 59, 597-604 (2006). Invited Review with cover picture. 8. Goodwin, AL, Chapman, KW and Kepert, CJ. Guest-dependent negative thermal expansion in nanoporous Prussian Blue analogues MIIPtIV(CN)6·x{H2O} (0 ≤ x ≤ 2; M = Zn, Cd). J. Am. Chem. Soc., 127, 17980-17981, 2005. 9. Chapman, KW, Chupas, PJ and Kepert, CJ. Direct observation of a transverse vibrational mechanism for negative thermal expansion in Zn(CN)2: An atomic pair distribution function analysis. J. Am. Chem. Soc., 127, 15630-15636, 2005. 10. Chapman, KW, Chupas, PJ and Kepert, CJ. Selective recovery of dynamic guest structure in a nanoporous prussian blue through in-situ X-ray diffraction: A differential pair distribution function analysis. J. Am. Chem. Soc., 127, 11232-11233, 2005. 11. Halder, GJ and Kepert, CJ. In-situ single crystal x-ray diffraction studies of desorption and sorption in a flexible nanoporous molecular framework material. J. Am. Chem. Soc., 127, 7891-7900, 2005. 12. Chapman, KW, Southon, PD, Weeks, CL and Kepert, CJ. Reversible hydrogen gas uptake in nanoporous prussian blue analogues. Chem. Commun., 3322-3324, 2005. 13. Kurmoo, M, Kumagai, H, Chapman, KW and Kepert, CJ. Reversible antiferromagnetic-ferromagnetic transformation upon dehydration-hydration in the porous metal-organic framework, [Co3(OH)2(C4O4)2]·3H2O. Chem. Commun., 3012-3014, 2005. 14. Goodwin, AL and Kepert, CJ. Negative thermal expansion and low-frequency modes in cyanide-bridged framework materials. Phys. Rev. B, 71, 140301, 2005. 58 School of Chemistry Professor Peter A Lay, FAA Room 307 School of Chemistry, F11 Telephone: +61 2 9351 4269 Facsimile: +61 2 9351 3329 Email: [email protected] http://www.chem.usyd.edu.au/about/staff_lay.html bioinorganic chemistry and electrochemistry Chemistry, Biochemistry and Cell Biology of Chromium in Relation to Cr-Induced Cancers and Cr Dietary Supplements (Bartholomäus, Codd, Foran*, Harris, Levina, Meejoo, Mulyani, Nguyen) The biochemistry of Cr(VI/V/IV/III), and their effects on cellular biology leading to Cr-induced cancers, have been studied. New methods have been developed for the synthesis of Cr(V)-diol and sugar complexes and their chemistry has been studied under conditions that are relevant to Cr-induced cancers. Empirical methods have been developed for determining the structures of Cr complexes in cells and tissues using linear combinations of XANES from model complexes that contain all of the ligand donor groups that are expected to be found in biology. These have been used to ascertain that the purported Cr-containing protein, chromodulin (a protein that is postulated to be involved in glucose metabolism), is likely to be an artifact of its isolation method. However, a new Cr-binding protein has been identified from blood serum when Cr(III) dietary supplements are allowed to react with the serum. We have obtained further evidence that Cr(III) dietary supplements are oxidised to carcinogenic Cr(VI) by certain enzymatic processes and that Cr(VI) and Cr(V) inhibit the same phosphatase enzymes and, in the same manner, as well-known vanadium anti-diabetic complexes, whereas the Cr(III) supplements themselves are inactive. Bioactive Ru and Mo Complexes (Gwee, Levina, Seuring) Considerable research has been conducted on the biotransformation of Ru anti-cancer drugs and Mo dietary supplements for the treatment of diabetes. We have used similar methodologies as those use in the Cr project to study the biotransformations in biological fluids and cells. In the case of molybdenum, molybdate and related species tend to dominate under most biological conditions, whereas Ru anti-cancer drugs undergo substantial hydrolysis and oligomerisation processes under physiological conditions and tend to bind with various proteins and cells. These studies are being used to understand the mode of action of the drugs and in the design of new Ru and Mo drugs. XAS Studies of Isolated and Intracellular Heme Proteins (Armstrong, Cai*, Cheng, Gell*, Harris, Lai*, Levina, Mackay*, Rayner*, Rich, Stocker*, Thomas*, Vogt*, Witting*) Raman and EPR spectroscopic and XAFS studies have shown that NO and CO adducts of a-Hb exhibit only minor changes to the heme centre on the binding of a-Hb stabilising protein (AHSP), which contrasts with the chemistry observed for the O2 adduct, which is converted to a low-spin Fe(III) complex with two axial histidines on AHSP binding. Experiments have been performed on the effects of hypoxia and then exposure to O2 with cardiac myocytes (heart muscle cells) under conditions that mimic ischemia reperfusion injury (heart damage after heart attacks). There is a general efflux of metal ions from the cytoplasm, which occurs well before apoptosis and this appears to be important in the initial damage to the tissues. Similar studies have also been conducted with neurons and these studies have been extended to develop new potential drugs for the treatment of heart attacks and strokes. Finally, the effect of induction of heme oxygenase-1 on mammalian cells has been studied in relation to its role in a variety of essential functions. Annual Research Report 59 Fullerenes: Derivatives, Conjugates and their Complexes (Armstrong, Boyd*, Carter, Gallagher, Sen Gupta) New fullerene/porphyrin conjugates have been prepared that have the potential to be powerful anti-cancer drugs and their physical and spectroscopic properties have been correlated with their biological activities using chemometric techniques. Cu Anti-inflammatory Drugs (Bonin, Dillon, Firkin, Hackett*, Hambley, Haque, Kennedy, Kaur, Kueh, McConaghy*, Nguyen, Reeve*, Rose*, Teo, Weder, Zhou) Cu-indomethacin and related pharmaceuticals were prepared and characterised by EPR spectroscopy and X-ray crystallography. The complexes are much less ulcerogenic than indomethacin and cause less renal damage that the muchtouted COX-II inhibitors. New formulations are being used internationally in veterinary applications and are planned enter human clinical trials for the treatment of inflammation and cancer. Detailed studies of the pharmacology of these drugs in rats have been undertaken, and new drugs with even higher efficacy and lower side effects have been developed and a raft of PCT and provisional patent applications have been filed for new compounds and indications. Cancer Diagnosis in Tissues and Identification of Microbes by Vibrational Spectroscopy (Ali, Armstrong, Carter, Mountford*, Rich, Russell*, Sorrell*, Tam) Multivariate analysis of microprobe vibrational spectroscopy was used to design new diagnostics for breast cancer, and in particular pre-cancerous lesions. Strong correlations have been obtained for vibrational spectroscopic diagnosis with diagnoses obtained form standard pathology studies and NMR techniques and chemometrics studies have been used to improve the identification of regions of cancer and to improve the diagnostic reliabilities. Vibrational spectroscopic techniques are also being developed to identify and differentiate pathogenic microorganisms and to examine their susceptibility to new drugs. Mushroom Tyrosinase (Gheibi, Levina) The binding of substrates to Cu in this enzyme have been studied by a number of spectroscopic and kinetic studies, as well as XAS. Selected Publications 1. Weder, JE, Dillon, CT, Hambley, TW, Kennedy, BJ, Lay, PA, Biffin, JR, Regtop, HL and Davies, NM. Copper complexes of nonsteroidal anti-inflammatory drugs: An opportunity yet to be realized. Coordination Chemistry Reviews, 232, 95-126, 2002. 2. Levina, A, Codd, R, Dillon, CT and Lay, PA. Chromium in biology: Nutritional aspects and toxicology. Progress in Inorganic Chemistry, 51, 145-250, 2003. 3. Kim, K-C, Hauke, F, Hirsch, A, Boyd, PDW, Carter, E, Armstrong, RS, Lay, PA and Reed, CA. Synthesis of the C59N+ carbocation. A monomeric azafullerene isoelectronic to C60. Journal of the American Chemical Society, 125, 4024-4025, 2003. 4. Mulyani, I, Levina, A and Lay, PA. Biological oxidation of chromium(III): Does the anti-diabetic activity of chromium(III) involve carcinogenic chromium(VI)? Angewandte Chemie, International Edition, 43, 4504-4507, 2004. 5. Feng, L, Gell, DA, Zhou, S, Gu, L, Kong, Y, Li, J, Hu, M, Yan, N, Lee, C, Rich, AM, Armstrong, RS, Lay, PA, Gow, AJ, Weiss, MJ, Mackay, JP and Shi, Y. Molecular mechanism of AHSP-mediated stabilization of a-hemoglobin. Cell, 119, 629-640, 2004. 6. Levina, A, Armstrong, RS and Lay, PA. Three-dimensional structure determination using multiple-scattering analysis of XAFS: Applications to metalloproteins and coordination chemistry. Coordination Chemistry Reviews, 249, 141-160, 2005. 7. Lay, PA and Levina, A. Mechanistic studies of relevance to the biological activities of chromium. Coordination Chemistry Reviews, 249, 281-298, 2005. 8. Immoos, CE, Sulc, F, Farmer, PJ, Czarnecki, K, Bocian, DF, Levina, A, Aitken, JB, Armstrong, RS and Lay, PA. Bonding in HNOmyoglobin as characterized by x-ray absorbance and resonance raman spectroscopies. Journal of the American Chemical Society, 127, 814-815, 2005. 9. Ramadan, S, Bonin, AM, Kennedy, BJ, Hambley, TW and Lay, PA. NMR analysis of indomethacin-induced gastric ulcers. Chemical Research in Toxicology, 18, 123-128, 2005. 10. Harris, HH, Levina, A, Dillon, CT, Mulyani, I, Lai, B, Cai, Z and Lay, PA. Time-dependent uptake, distribution and biotransformation of chromium(VI) in individual and bulk human lung cells: Application of synchrotron radiation techniques. Journal of Biological Inorganic Chemistry, 10, 105-118, 2005. 11. Levina, A, Harris, HH and Lay, PA. Binding of chromium(VI) to histones: Implications for chromium(VI)-induced genotoxicity. Journal of Biological Inorganic Chemistry, 11, 225-234, 2006. 12. Witting, PK, Harris, HH, Rayner, BS, Aitken, JB, Dillon, CT, Stocker, R, Lai, B, Cai, Z, Lay, PA. The endothelium-derived hyperpolarizing factor, H2O2, promotes metal ion efflux in aortic endothelal cells. Elemental mapping by a hard X-ray microprobe. Biochemistry, 45, 12500-12509, 2006. 60 School of Chemistry Emeritus Professor Leonard F Lindoy, FAA Honorary Staff Room 146 School of Chemistry, F11 Telephone: +61 2 9351 2734 Facsimile: +61 2 9351 3329 Email: [email protected] http://www.chem.usyd.edu.au/about/staff_lindoy.html Annual Research Report 61 cationic tetrahedral cage structures capable of including tetrahedral anions (such as BF4-, PF6- and FeCl4-) have been constructed, in this case using self assembly techniques. Molecular Electronics and Sensors (Bray, Wei, Herrmann*, Müller*) This project is being carried out jointly with the CSIRO Division of Industrial Physics. It is concerned with the synthesis and investigation of organic cross-linked gold nanoparticle films, with emphasis on their electrical properties. Attention is being given to both the theoretical consequences of nanoparticle size and cross-linking as well as to the potential practical applications of these unusual materials metallosupramolecular chemistry Metallo-Supramolecular Chemistry: Metal-Directed Synthesis of Molecular Architectures Including Triangles, Tetrahedra, and Molecular Frameworks (Bray, Clegg, Gloe*, Jolliffe, Meehan*, Murray*, McMurtrie*) The synthesis of unusual supramolecular architectures employing metal directed procedures and incorporating linked β-diketonato ligand systems has been carried out. This project is aimed at using the latent directional and electronic information in molecules and ions (including metal ions) to assemble new supramolecular materials showing unusual properties. Macrocycle Design and Synthesis for Metal Ion Recognition (Bray, Meehan*, Vasilescu*, Wei, ) This project has involved the design and synthesis of new macrocylic systems incorporating mixed donor sets that are capable of binding selected transition and post-tranistion metal ions selectively. New Framework Materials: Self-Assembly of New Hydrogen Bonded and Metal-Ion Linked Arrays (Bishop, Clegg, McMurtrie, Turner) The project is concerned with the design and synthesis of new molecular architectures incorporating linked macrocyclic and related systems as structural components – with emphasis being given to the use of hydrogen bonded or metal-donor atom links in the bridges between macrocyclic rings.. As such, the project represents an extension of our previous studies in which a number of different macrocyclic rings have been linked covalently by means of conventional organic synthetic procedures. In particular, the new species are designed to form linked products by means of self-assembly processes - thus offering synthetic economy in the construction of the novel materials. New Reagents for Selective Metal Cation, Anion and Metal Salt Extraction and Membrane Transport (Galbraith, Gloe*, Tasker*) In this project the design and synthesis of new reagents for use in solvent extraction and bulk membrane transport experiments is being carried out. Recent results include the successful selective membrane transport of individual anions and the use of ditopic receptors for metal salt extraction. New Cage Receptors for Metal Ions and anions (Clegg, Glasson*, Murray*, Meehan*, Perkins, Turner) We have undertaken the construction of a range of new cage and cage-like molecules for the selective binding of both cations and anions. These include an inherently chiral supra-cage. The cage interacts with a single octahedral metal ion such that a helical twist extends about 22 angstroms along the axial length of the system. In other studies unusual Selected Publications 1. Lindoy, LF and Atkinson, IM. Self-assembly in supramolecular chemistry. Royal Society for Chemistry, Cambridge UK - a monograph of 219 pp, 2000. 2. Armstrong, RS, Atkinson, IM, Carter, E, Mahinay, MS, Skelton, BW, Turner, P, Wei, G, White, AH and Lindoy, LF. Self-assembly directed by NH-O hydrogen bonding: New layered molecular arrays derived from 4-tert-butylbenzoic acid and aliphatic diamines. Proc. Nat. Acad. Sci., 99, 4987-4992, 2002. 3. Bray, DJ, Liao, L-L, Antonioli, B, Gloe, K, Lindoy, LF, McMurtrie, JC, Wei, G and Zhang, X-Y. Assembly of a tri-silver metallo capsule – synthesis, X-ray structure and membrane transport behaviour. Dalton Trans., 2082-2083, 2005 4. Bishop, MM, Lindoy, LF, Parkin, A and Turner, P. Towards a system for the systematic structural study of intermolecular interactions in crystals of transition metal complexes. Dalton Trans., 2563-2571, 2005. 5. Clegg, JK, Lindoy, LF, McMurtrie, JC and Schilter, D. Dinuclear bis-beta-diketonato ligand derivatives of iron(III) and copper(II) and use of the latter as components for the assembly of extended metallo-supramolecular structures. Dalton Trans., 857-864, 2005. 6. Antonioli, B, Clegg, JK, Bray, DJ, Gloe, K, Gloe, K, Heßke, H and Lindoy, LF. An unprecedented bridging [Ag2(NO3)6]4– anion as a component of aninfinite silver(I) molecular ladder incorporating a dinuclear cationic silver complex of a bis-dipyridylamine ligand. Cryst.Eng.Comm., 8, 748-750, 2006. 7. Perkins, DF, Lindoy, LF, McAuley, A, Meehan, GV and Turner, P. Manganese(II), iron(II), cobalt(II) and copper(II) plexes of an extended inherently chiral tris-bipyridyl cage. Proc. Nat. Acad. Sci., 103, 532-537, 2006. 8. Self-assembled metallo-supramolecular systems incorporating beta-diketone motifs as structural elements. Bray, DJ, Clegg, JK, Lindoy, L.F and Schilter, D in Advances in Inorganic Chemistry, Eds. van Eldik, R and Bowman-James, K. Academic Press, Volume 59, 1-37, 2007. 62 School of Chemistry Dr Christopher Ling Room 455 School of Chemistry, F11 Telephone: +61 2 9351 4780 Facsimile: +61 2 9351 3329 Email: [email protected] http://www.chem.usyd.edu.au/about/staff_ling.html neutron scattering and materials science Incommensurate Misfit-layered Thermoelectric Cobaltates (Schmid) Misfit-layered cobaltates are a family of layered ceramic oxides attracting considerable attention for their excellent properties as thermoelectrics (allowing the direct conversion of a thermal gradient into an electrical current for power generation, or vice versa for heating/cooling applications). Their defining structural feature is the stacking of alternating layer types: a pseudo-hexagonal CdI2-type layer of edge-sharing CoO6 octahedra (H subsystem); and 3 or 4 pseudo-tetragonal rock-salt-type metal oxide layers (RS subsystem). A lattice mismatch between these two types of layers means that these oxides must be described crystallographically as incommensurately modulated composites. A large number of misfit-layered cobaltates are known, incorporating various solid solutions of metal ions into the cation sites of the RS subsystem. One of the most intensively studied, [Ca2CoO3]RS[CoO2]H1.61, is notable for its unusually high thermopower, straightforward synthetic procedure and the presence of only two cation species. Adding to the interest in this phase are the simultaneous presence of cobalt in three oxidation states (II, III, IV) and observations of giant magnetoresistance and three magnetic transitions. Recently, it has been found that a significant number of oxygen vacancies exist in the structure, but their actual location had not been determined. Furthermore, the oxygen content was found to vary according to synthetic procedure, suggesting a possible means of controlling the physical properties - the thermoelectric power was found to increase with the number of oxygen vacancies. In this study [6], we used single crystal X-ray diffraction to locate the oxygen vacancies on the disordered oxygen site in the central layer of the RS subsystem. As-made samples contain 14(2) % oxygen vacancies on this site, while a further ~13 % vacancies can be introduced by high-temperature annealing under mildly reducing atmospheres. Doping Nd3+ for Ca2+ was found to substantially reduce the tolerance of the structure for oxygen vacancies to ~4 % on the disordered site, while doping Ti4+ for Co2+/3+/4+ was found to decrease the number of oxygen vacancies while maintaining the same average cobalt oxidation state of 3.13+. Ti4+ was located on the disordered cobalt site in the central layer of the RS subsystem. The RS subsystem therefore appears to be responsible for all the flexibility of this compound, with the H subsystem (which shows no sign at all of oxygen vacancies or cation doping) responsible for maintaining its structural integrity. Novel Transition Metal Networks Within Stabilised Oxygen-Ion Conductors The excellent ionic conduction properties of the high-temperature phase of bismuth oxide, δ-Bi2O3, derive from the 25% oxygen vacancies in its disordered fluorite-type structure. Although only stable above 937 K, its fluorite-type substructure and ionic conduction can be preserved to room temperature when doped with 5+ or 6+ valent transition metal cations such as Nb(V), Ta(V), W(VI), or Mo(VI), which localise some of the oxygen vacancies. These doped δ-Bi2O3-related Annual Research Report 63 phases have extremely complex superstructures that are largely invisible to X-ray powder diffraction (XRD) due to the dominant X-ray scattering power of Bi over O. In the absence of single crystals, only neutron powder diffraction (NPD) data can be relied upon to solve and refine these superstructures; however, NPD suffers from the opposite problem to XRD in that it often contains too much evenly-weighted information, making it hard to find an unambiguous and reliable solution. This project concerns the insertion of unpaired d electrons into the unique transition metal networks found in these superstructures, in order to elicit novel low-dimensional and geometrically frustrated magnetic states. In the first stage we have revisited some of the most complex of these superstructures that were never previously solved by diffraction methods. We have found that ab initio quantum calculations, using the localised density approximation (LDA) to density functional theory (DFT), are remarkably effective at perturbing the fluorite-type oxygen sublattice surrounding dopant transition metal cations. The structures of Bi14MO24 (M = Cr, Mo, W) [3] and Bi94Nb32O221 [4] could be solved by DFT geometry optimisation, starting from a simple model based only on the distribution of the dopant metal cations (which could be unambiguously determined using XRD). The optimised structures almost perfectly fit experimental NPD data, subsequent Rietveld-refinement leading to atomic shifts of less than 0.1 Å. The figure shows the oxygen atom coordination around M atoms in Bi14MO24 that results from the 8-fold crystallographic disordering of the highly ordered MO4 tetrahedra identified in the DFT-optimised structure. Multiferroic Layered Oxides (Kennedy) Multifunctional crystalline materials, in which several physical properties (magnetic, electronic, and/or structural) co-exist and interact on the atomic scale, are of great scientific and technological interest. This project concerns multiferroic oxides that exhibit both ferroelectricity (an electrical polarisation due to atomic displacements, used in capacitors) and ferromagnetism (a long-range spin polarisation due to magnetic exchange interactions, used in transformers and data storage). Multiferroics are of interest for applications as sensors and actuators, particularly in microwave devices, and as magnetically recordable ferroelectric (non-volatile) data storage media. Very few materials exhibit truly multiferroic behaviour, because ferroelectricity generally requires d0 transition-metal ions (e.g. Ti4+) while ferromagnetism requires the presence of mobile d electrons, i.e., the two properties are mutually exclusive in simple oxides. Most applied research into multiferroics therefore focuses on layered composites of ferroelectric and ferromagnetic oxides manufactured by techniques such as chemical vapour deposition. However, such ‘artificially’ layered oxides are far coarser and less homogeneous than ‘naturally’ layered oxides, the potential of which remains relatively unexplored. In this project we are using the naturally layered Aurivillius phase oxides as templates for multiferroicity. Aurivillius phases consist of ordered intergrowths of α-PbO-type layers of composition [Bi2O2]2+ and n perovskite-type layers of composition [An-1BnO3n+1]2-, where A is a large cation such as Bi3+ or Pr3+, and B is a small cation such as Nb5+ or Ti4+. Aurivillius phases are strongly ferroelectric due to displacements of A and B cations within the perovskite-type layers. Our goal is to substitute magnetic cations such as Fe3+ and Mn4+ into the B sites of the central perovskite-type layers (light grey octahedra) in order to make them ferromagnetic, while leaving non-magnetic cations in the outer perovskite-type layers (white octahedra) so that they remain ferroelectric. Thus far we have achieved partial layers of Mn4+, Ru4+ and Ir4+ [2]; and Cr3+, Mn3+, Fe3+ and Co3+. Selected Publications 1. Ling, CD and Johnson, M. Modelling, refinement and analysis of the “type III” d-Bi2O3-related superstructure in the system Bi2O3-Nb2O5. Journal of Solid State Chemistry, 177, 1838-1846, 2004. 3. Ling, CD. Solving d-Bi2O3-related superstructures by combining neutron powder diffraction and ab initio calculations. Physica B, 385-386, 193-195, 2006. 5. Hunger, J, Beta, IA, Böhlig, H, Ling, CD, Jovic, H and Hunger, B. Adsorption structures of water in NaX studied by DRIFT spectroscopy and neutron powder diffraction. Journal of Physical Chemistry B, 110, 342-353, 2006. 1. Ling, CD, Aivazian, K, Schmid, S and Jensen, P. Structural investigation of oxygen non-stoichiometry and cation doping in misfitlayered thermoelectric [Ca2CoO3-x][CoO2]d, d ≈ 1.61. Journal of Solid State Chemistry, 180, 1446-1455, 2007. 2. Sharma, N, Ling, CD, Wrighter, GE, Chen, PY, Kennedy, BJ and Lee, PL. Three-layer aurivillius phases containing magnetic transition metal cations: Bi2‑xSr2+x(Nb,Ta)2+xM1‑xO12, M = Ru4+, Ir4+, Mn4+, x ≈ 0.5. Journal of Solid State Chemistry, 180, 370-376, 2007. 6. Ling, CD, Avdeev, M and Aivazian, K. Synthesis, structure, and stability of the high-Ttemperature 6H-type perovskite phase Ba3BaSb2O9. Acta Crystallographica Section B, In Press. 64 School of Chemistry Dr Nigel T Lucas Room 516 School of Chemistry, F11 Telephone: +61 2 9351 2745 Facsimile: +61 2 9351 3329 Email: [email protected] http://www.chem.usyd.edu.au/about/staff_lucas.html Annual Research Report 65 Large Polycyclic Aromatic Hydrocarbons as π-Ligands (Müllen†, El Hamaoui†) One of the difficulties in dealing with larger PAHs is that with increasing molecular weight, the solubility of the compounds decreases, primarily as a result of strong aggregation of the discs through π-π interactions. The processability of large PAHs can be dramatically improved through the coordination of metal fragments to the disc surface to suppress the formation of extended aggregates. Additionally, site-selectivity as a result of the multiplicity of available coordination sites provides information about the electronic properties of the PAH. The [Ru(η5-C5Me5)]+ fragment binds to one of the peripheral rings of HBC(t-Bu)6 to afford the crystallographically-confirmed sandwich complex 3 as the major product (triflate anion not shown). The related complex [Ru(η5-C5Me5)(η6-HBC)]OTf (4) affords graphitic nanorods when subjected to controlled solid-state pyrolysis, serving as both metal catalyst and carbon source. SYNTHETIC & SUPRAMOLECULAR CHEMISTRY The identification and subsequent bulk preparation of the fullerenes in the mid- to late-1980’s ignited the rapid growth of synthetic work on carbon allotropes and new carbon-rich materials. More recently, advances in the synthesis of large polycyclic aromatic hydrocarbons (PAHs) have allowed the efficient preparation of monodisperse ‘synthetic graphites’ (graphenes) of unprecedented size. When functionalised with long alkyl chains, these soluble disc-like molecules can self-assemble, through strong π-π interactions, into columnar liquid crystalline mesophases which have shown promise as semiconductor materials. Our key projects extend on previous work with large PAHs through the investigation of their coordination chemistry and the characterisation of metal-containing adducts. Metallographic Discs (Darwish, Müllen†, Wu†) By varying the number and type of ligated metal centres bound to the graphitic discs, it is possible that the supramolecular ordering of the discs can be controlled and their molecular physical properties tuned. The most intensively studied of the PAHs described above is hexa-peri-hexabenzocoronene (HBC, C42H18), and it can be rationally synthesised in good yield with a wide range of functionalities and substitution patterns. Using an appropriately functionalised precursor disc, 1-6 ligated metal centres can be introduced around the core periphery. When the ligands are rigid and bulky, crystalline materials are obtained, whereas the use of ligands with long, flexible, alkyl chains can afford materials with liquid crystalline properties. Complexes bearing one or two HBC-based ligands with pyridine, bipyridine (1), phosphine or cyclopentadienyl (2) coordinating groups are have been prepared and characterised. Assembly and Imaging of Graphitic Molecules at Surfaces (Zareie†, McDonagh†) Investigations into the self-organization of a wide range of organic compounds at surfaces has been revolutionized by the direct imaging of chemical species using scanning probe microscopies. To complement the supramolecular studies of new PAH-based ligands and metal complexes in the bulk, their 2-dimensional self-assembly at highly-ordered surfaces is being explored using scanning tunnelling microscopy (STM). The relative importance of intermolecular and molecular-surface interactions are being assessed by systematic variation of the molecular shape and functional group substitution. For example, the graphite surface assembly of the pyridine-substituted HBC(C12H25)5(4-py) ligand and its bis-axially substituted Ru(phthalocyanine) derivative are dramatically different. Immobilisation of Metal Complexes on Oxide Surfaces (McDonagh†, Colbran†, Hook†, Dance†) Palladium, platinum and tungsten complexes containing the bifunctional ligand (diphenylphosphino)catechol have been synthesized. The catecholate functionality strongly binds to titanium dioxide nanoparticles allowing the complexes to be effectively anchored to the TiO2 surface. Solid state 31P NMR spectroscopy has been used to probe the surface-bound compounds. Diffuse reflectance infra-red spectroscopy provides data on surface-bound tungsten carbonyl complexes. The palladium phosphine complex [PdBr2{PPh2(4catechol)}2] supported on TiO2 effectively catalyses the coupling of phenylacetylene with 4-nitroiodobenzene. A crystal structure of cis-[PtBr2{PPh2(4-catechol)}2]·(ethanol)2 reveals two catechol rings well disposed to act as double bidentate ligands for adjacent metal atoms on the surface of a nanocrystal of TiO2 and provides geometric parameters for the computational modelling of such a process. † Co-worker not associated with The University of Sydney Selected Publications 1. Lucas, NT, McDonagh, AM, Dance, IG, Colbran, SC and Craig, DC. cis-[PtBr2{PPh2(4-catechol)}2]: synthesis, crystal structure, and computational modelling of its binding to nanocrystalline TiO2. Dalton Trans., 680–685, 2006. 2. Cifuentes, MP, Powell, CE, Morrall, JP, McDonagh, AM, Lucas, NT, Humphrey, MG, Samoc, M, Houbrechts, S, Asselberghs, I, Clays, K, Persoons, A, Isoshima, T. Electrochemical, spectroelectrochemical, and molecular quadratic and cubic nonlinear optical properties of alkynylruthenium dendrimers. J. Am. Chem. Soc., 128, 10819–10832, 2006. 3. Usher, AJ, Lucas, NT, Dalton, GT, Randles, MD, Viau, L, Humphrey, MG, Petrie, S, Stranger, R, Willis, AC, Rae, AD. Mixedmetal cluster chemistry. 29. Core expansion and ligand-driven metal exchange at group 6-iridium clusters. Inorg. Chem., 45, 10859–10872, 2006. 4. Chow, H, Dean, PAW, Craig, DC, Lucas, NT, Scudder, ML and Dance, IG. The subtle tetramorphism of MePh3P+I3-. New J. Chem., 27, 704–713, 2003. 5. Samoc, A, Samoc, M, Luther-Davies, B, Freydank, AC and Lucas, NT. Investigation of nonlinear optical chromophores with femtosecond degenerate four-wave mixing in solutions. J. Nonl. Opt. Phys. Mater., 12, 235–246, 2003. 6. Lucas, NT, Notaras, EGA, Petrie, S, Stranger, R and Humphrey, MG. Mixed-metal cluster chemistry. 22. Synthesis and crystallographic, electrochemical, and theoretical studies of alkyne-coordinated group 6-iridium clusters linked by phenyleneethylnylene groups. Organometallics, 22, 708–721, 2003. 7. Lucas, NT, Notaras, EGA, Cifuentes, MP and Humphrey, MG. Mixed-metal cluster Chemistry. 21. Synthesis and crystallographic and electrochemical studies of alkyne-coordinated group 6–iridium clusters linked by phenylenevinylene groups. Organometallics, 22, 284–301, 2003. 8. Lucas, NT, Blitz, JP, Petrie, S, Stranger, R, Humphrey, MG, Heath, GA and Otieno-Alego, V. Mixed-metal cluster chemistry. 19. Crystallographic, spectroscopic, electrochemical, spectroelectrochemical, and theoretical studies of systematically varied tetrahedral group 6–iridium clusters. J. Am. Chem. Soc., 124, 5139–5153, 2002. 9. Lucas, NT, Humphrey, MG and Rae, AD. Mixed-metal cluster chemistry. 16. Syntheses of oligourethanes containing clusters in the backbone. Macromolecules, 34, 6188–6195, 2001. 66 School of Chemistry Annual Research Report Associate Professor John Mackie Selected Publications Honorary Staff Room 146 School of Chemistry, F11 Telephone: +61 2 9351 2734 Facsimile: +61 2 9351 3329 Email: [email protected] http://www.chem.usyd.edu.au/about/staff_mackie.html chemical reactions at high temperature Theoretical Studies in Combustion Chemistry (Bacskay) Reactions of the NH radical are most important in combustion especially in understanding the mechanism of NOx formation when air is the oxidant. NH reactions are also important in processes such as the Thermal De-NOx technique for reduction of NO in combustion systems. NH has been found experimentally to react rapidly with H2, H2O and CO2, all important components of combustion gases. Using Gaussian techniques we have been investigating the elementary mechanisms whereby NH reacts with these three species. The reaction between NH and H2 is a straightforward abstraction reaction to produce NH2 and H. However, the reactions with H2O and CO2 are complex. Several intermediates have been located on both triplet and singlet reaction potential energy surfaces for NH + CO2 with the occurrence of intersystem crossing. The NH + H2O surface is also complex with several low energy intermediates having been located on the singlet surface but with no stable intermediates on the triplet surface. Conversion of Halons into Useful Chemicals (Dlugogorski*, Kennedy*) The use of halon fire suppressants such as CHF3 are now banned under the Montreal Protocol because they are significant ozone depleting agents. There is a pressing need to convert the large stockpiles of halons into useful chemicals. Together with colleagues at the University of Newcastle, the reaction between CHF3 and methane to produce the valuable industrial chemical, CH2CF2, is being studied theoretically using Gaussian techniques, and in the laboratory in flow reactors. An important intermediate reaction in the mechanism leading to the formation of CH2CF2 is the reaction between CH3 radicals and the carbene, CF2. A detailed quantum chemical and kinetic study has revealed that this reaction proceeds via an intermediate, CH3CF2 via chemical activation. The intermediate is, however, not stable and rapidly fissions of an H atom producing the desired CH2CF2. Rate constants for the overall mechanism have been derived using a multiwell kinetic approach. Dioxins from Combustion of Wood (Dlugogorski*, Kennedy*) Wood treated by preserving agents incorporating organochlorine pesticides can lead to the emission of the environmentally harmful polychlorinated dioxins and dibenzofurans upon combustion or incineration. The chemical reaction pathways leading to dioxin formation are being investigated experimentally in the laboratory using TGA, DSC and mass spectrometry and theoretically using quantum chemical techniques. Reaction pathways to chlorinated dibenzofuran from the organochlorine pesticide, permethrin, have been identified by Gaussian techniques and reaction path analysis carried out. Further quantum chemical studies are being carried out of reaction pathways which can lead to the complete destruction of dibenzofurans in incineration. 67 1. Hynes, RG, Mackie, JC and Masri, AR. Inhibition of premixed hydrogen-air flames by 2-H heptafluoropropane. Combust. Flame, 113, 554-565, 1998. 2. Bacskay, GB, Martoprawiro, M and Mackie, JC. The thermal decomposition of pyrrole: An ab initio quantum chemical study of the potential energy surface associated with the hydrogen cyanide plus propyne channel. Chem. Phys. Letters, 300, 321-330, 1999. 3. Hynes, RG, Mackie, JC and Masri, AR. A shock tube study of the pyrolysis of the halon replacement molecule, CF3CHFCF3. J. Phys. Chem. A, 103, 54-61, 1999. 4. Martoprawiro, M, Bacskay, GB and Mackie, JC. Ab initio quantum chemical and kinetic modeling study of the pyrolysis kinetics of pyrrole. J. Phys. Chem. A, 103, 3923-3934, 1999. 5. Haworth, NL, Smith, MH, Bacskay, GB and Mackie, JC. Heats of formation of hydrofluorocarbons obtained by gaussian-3 and related quantum chemical calculations. J. Phys. Chem. A, 104, 7600-7614, 2000. 6. Haworth, NL, Bacskay, GB and Mackie, JC. The role of phosphorus dioxide in the H+OH recombination reaction: Ab initio quantum chemical computation of thermochemical and rate parameters. J. Phys. Chem. A, 106, 1533-1541, 2002. 7. Mackie, JC, Bacskay, GB and Haworth, NL. Reactions of phosphorus-containing species of importance in the catalytic recombination of H + OH: Quantum chemical and kinetic studies. J. Phys. Chem. A, 106, 10825-10830, 2002. 8. Haworth, NL, Mackie, JC and Bacskay, GB. An ab initio quantum chemical and kinetic study of the NNH + O reaction potential energy surface: How important is this route to NO in combustion? J. Phys. Chem. A, 107, 6792-6803, 2003. 9. Bacskay, GB and Mackie, JC. Oxidation of CO by SO2: A theoretical study. J. Phys. Chem. A, 109, 2019-2025, 2005. 10. Mackie, JC and Bacskay, GB. Quantum chemical study of the mechanism of reaction between NH (X 3S) and H2, H2O, and CO2 under combustion conditions. J. Phys. Chem. A, 109, 11967-11974, 2005. 11. Hai Yu, Mackie, JC, Kennedy, EM and Dlugogorski, BZ. Experimental and quantum chemical study of the reaction CF2 + CH3 ↔ CF2CH3 → CH2:CF2 + H: A key mechanism in the reaction between methane and fluorocarbons. Ind. Eng. Chem. Res., 45, 3758-3762, 2006. 68 School of Chemistry Professor Thomas Maschmeyer Room 303 School of Chemistry, F11 Telephone: +61 2 9351 2581 Facsimile: +61 2 9351 3329 Email: [email protected] http://www.chem.usyd.edu.au/about/staff_maschmeyer.html green chemistry/processes, functional nano-materials and high throughput experimentation General The world is standing at the technological threshold of a revolution that is driven by the need for truly sustainable (industrial) processes. At current rates of resource usage, a world population operating with Australian standards of living would require between 4 – 6 planets (depending on the method of calculation). Clearly, this is untenable and, from a chemical viewpoint, the inherent challenges can only be met by devising strategies for waste reduction, energy optimisation and process intensification as outlined in the 12 principles of “Green Chemistry”. Our group aims to tackle these issues by generating and using new fundamental insights on the molecular and nanoscopic level to develop feasible leads for the design of new catalytic chemical routes and processes that will enhance sustainability. Examples of project areas: • New ionic liquids (supported and/or chiral) as catalytic and synthesis media. • Preparation, characterisation and testing of ceramic nanoparticles stabilised and supported in mesoporous hosts as catalysts and functional materials. • Micro-wave assisted synthesis for green chemistry. • Functional coatings on microstructured reactors. • Chemistry in supercritical solvents. • Converting biomass to biofuel. • Hydrogen generation from water. Annual Research Report 69 Brief Curriculum Vitae In 1994, as Australian Bicentennial Fellow, Thomas Maschmeyer went to the Royal Institution, London. Subsequently, he was made Assistant Director of their Davy Faraday Laboratories and also Associate Lecturer and Affiliated Fellow (Peterhouse) at the University of Cambridge. In 1998, at the age of 31, he was appointed Professor and Head of the Department of Industrial Organic Chemistry at the Delft University of Technology, making him the youngest Professor of Chemistry in Europe at that time. Additionally, in 2000, Thomas became Vice-Chairman of the Delft Institute of Chemical Technology. During this time he was also advisor to the Dutch Federal Ministry of Finance and Economic Affairs. He returned to his alma mater in late 2003, when he commenced his new positions as Federation Fellow and Professor of Chemistry. Recent highlights include: his founding role in ‘Avantium’ (a Dutch spin-off company with ca. 100 employees, specialising in High-Throughput Experimentation Research), the design of the ‘grafting approach’ (leading to highly selective catalysts via the use of molecularly confined spaces) and the design of new types of mesoporous materials. Both design approaches lead to catalysts that are superior to their industrial counterparts and are part of on-going industrial development/up-scaling programmes. He also devised and commissioned ceramic membrane reactors that represent new technological solutions to many chemical process problems, as they allow conversion and separation to occur simultaneously, with the added benefit of being able to operate beyond the reaction equilibrium. Selected Publications 1. Maschmeyer, Th, Rey, F, Sankar, G and Thomas, JM. Heterogeneous catalysts obtained by grafting metallocene complexes onto mesoporous silica. Nature, 378, 159-162, 1995. 2. Oldroyd, RD, Thomas, JM, Maschmeyer, Th, MacFaul, PA, Snelgrove, DW, Ingold, KU and Wayner, DDM. The titanium(IV) catalysed epoxidation of alkenes by tert-alkyl hydroperoxides. Angewandte Chemie, IEE., 35, (23/24), 2787-2789, 1997. 3. Maschmeyer, Th, Oldroyd, RD, Sankar, G, Thomas, JM, Shannon, IJ, Klepetko, JA, Masters, AF, Beattie, JK and Catlow, CRA. Designing a solid catalyst for the selective low-temperature oxidation of cyclohexane to cyclohexanone. Angewandte Chemie, IEE., 36, (15), 1639-1642, 1997. 4. Shephard, DS, Maschmeyer, Th, Johnson, BFG, Thomas, JM, Sankar, G, Ozkaya, D, Zhou, W, Oldroyd, RD and Bell, RG. Bimetallic nanoparticle catalysts anchored inside mesoporous silica. Angewandte Chemie, IEE., 36, (20), 2242-2245, 1997. 5. Zhou, W, Thomas, JM, Shephard, DS, Johnson, BFG, Ozkaya, D, Maschmeyer, Th, Bell, RG and Ge, Q. Ordering of ruthenium cluster carbonyls in mesoporous silica. Science, 280, (5364), 705-708, 1998. 6. Shephard, DS, Zhou, W, Maschmeyer, Th, Matters, JM, Roper, CL, Parsons, S, Johnson, BFG and Duer, MJ. Site directed surface derivatisation of MCM 41 – Use of high-resolution transmission electron-microscopy and molecular recognition for determining the position of functionality within mesoporous materials. Angew. Chem. Int. Ed. Eng., 37, (19), 2719-2723, 1998. 7. Nowotny, M, Maschmeyer, Th, Johnson, BFG, Lahuerta, P, Thomas, JM and Davies, JE. Heterogeneous dinuclear rhodium(II) hydroformylation catalysts – performance evaluation and silsesquioxane-based chemical modeling. Angewandte Chemie, IEE., 40, (5), 955-958, 2001. 8. Pescarmona, PP, Van der Waal, JC, Maxwell, IE and Maschmeyer, Th. A new efficient route to titanium-silsesquioxane epoxidation catalysts developed using high-speed experimentation techniques. Angewandte Chemie, IEE., 40, (4), 740-743, 2001. 9. Shan, Z, Gianotti, E, Jansen, JC, Peters, JA, Marchese, L and Maschmeyer, Th. One-step synthesis of a highly Active mesoporous titanium-containing silica by using bifunctional templating. Chemistry – A European Journal, 7, (7), 1437-1443, 2001. 10. Nowotny, M, Pedersen, LN, Hanefeld, U and Maschmeyer, T. Increasing the ketone selectivity of the cobalt-catalyzed radical chain oxidation of cyclohexane. Chemistry – A European Journal, 8, (16), 3724-3731, 2002. 11. Maschmeyer, T. Assembled catalysts – just interesting, or maybe important? Topics in Catalysis, 24, 29-36, 2003. 12. Pescarmona, PP, Van der Waal, JC and Maschmeyer, T. Silsesquioxane-based homogeneous and heterogeneous epoxidation catalysts developed by using high-speed experimentation. Chemistry – A European Journal, 10, (7), 1657-1665, 2004. 13. Pescarmona, PP, Van der Waal, JC and Van de Water, LGA. Parallel approaches to the synthesis and testing of catalysts for liquidphase reactions, in: High throughput screening in chemical catalysis. Eds. Hagemeyer, A, Strasser, P and Volpe jnr., AF, Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, 211-237, ISBN: 3-527-30814-8, 2004. 14. Simons, C, Hanefeld, U, Arends, IWCE, Sheldon, RA and Maschmeyer, T. Noncovalent anchoring of asymmetric hydrogenation catalysts on a new mesoporous aluminosilicate: Application and solvent effects. Chemistry – A European Journal, 10, (22), 5829-5835, 2004. 15. Simons, C, Hanefeld, U, Arends, I, Minnaard, AJ, Maschmeyer, T and Sheldon, RA. Efficient immobilisation of Rh-MonoPhos on the aluminosilicate AlTUD-1. Chemical Communications, (24), 2830-2831, 2004. 16. Klomp, D, Djanashvili, K, Svennum, NC, Chantapariyavat, N, Wong, C-S, Vilela, F, Maschmeyer, T, Peters, JA and Hanefeld, U. Combined epimerization and acylation: Meerwein-Ponndorf-Verley-Oppenauer catalysts in action. Organic & Biomolecular Chemistry, 3, (3), 483-489, 2005. 17. Veum, L, Kanerva, L, Halling, PJ, Maschmeyer, Th and Hanefeld, U. Optimization of the enantioselective synthesis of cyanohydrin esters. Advanced Synthesis & Catalysis, 347, (7&8), 1015-1021, 2005. 18. Simons, C, Hanefeld, U, Arends, IWCE, Maschmeyer, Th and Sheldon, RA. A one-pot enantioselective chemo-enzymatic synthesis of amino acids in water. Advanced Synthesis & Catalysis, 348, (4&5), 471-475, 2006. 19. Hamdy, MS, Berg, O, Jansen, JC, Maschmeyer, Th, Moulijn, JA and Mul, G. TiO2 nanoparticles in mesoporous TUD 1: Synthesis, characterization and photocatalytic performance in propane oxidation. Chemistry – A European Journal, 12, (2), 620-628, 2006. 70 School of Chemistry Dr Craig P Marshall Room LG82a, Madsen Building F09 School of Chemistry, F11 Telephone: +61 2 9351 3994 Facsimile: +61 2 9351 3329 Email: [email protected] Annual Research Report 71 obtained from the bitumen indicated similarities with hydrothermal petroleum generated in the Guaymas Basin (Gulf of California) where hot waters permeate organic-rich sediments and generate oil with a distinctive chemistry. We have found a closely comparable suite of hydrocarbons in the McArthur River deposit. Determining the taxonomic affinities of microbes in the mesophilic zone surrounding the orebody has been very successful. Significantly we have discovered a dinoflagellate affinity for some of the micro-eukaryote fossils. Furthermore, we are currently developing a new line of investigation to elucidate the biological affinities of these enigmatic microfossils by the application of synchrotron IR micro-spectroscopy at NSRRC Taiwan. This is the first application of synchrotron techniques applied to micro-eukaryote fossils. The project was awarded an ARC Discovery Project in 2004. A comparable study of Early Archaean hydrothermal deposits in the Pilbara region has also been undertaken. We have also started investigating modern hydrothermal deposits in Yellowstone National Park. Contemporary Ancient Analogue Micro-Organisms of Palaeobiological Significance (Neilian8, Burns8) Biogeochemistry Our current research interests cover a number of projects which investigate the diversity and timelines of the early forms of life from the fossil record. In addition, interpretation is maximized when careful observations on ancient populations are combined with actualistic studies of microbial populations in comparable modern environments. Although many geochemical reactions may be affected by microbial metabolism in geothermal environments the interactions between microbes and geothermal solutions are poorly understood. Experiments are been conducted that hope to investigate at the molecular level, the interaction between a polymerizing silica solution and metallic solutions that simulate processes occurring in near-Earth surface geothermal systems. Silicification and metal sorption experiments are been conducted on filamentous cyanobacteria Calothrix sp., Phormidium sp. and halophilic archaea Halobacterium sp. These micro-organisms are isolated and cultured from commonly occurring microbes in stromatolites from Shark Bay (Western Australia). The silicification and metal sorption experiments are performed on healthy cultures in growth phase by adding solutions of SiO2, Cu2+, Fe2+, and Pb2+. The extent of sorption and characterisation of the biological-mineral interfaces will be determined by Raman micro-spectroscopy, FTIR and SR FTIR micro-spectroscopies. 1 Tracing the Origins of Life in Earth’s Oldest Sedimentary Rocks (Love 1, Summons2, Allwood3, Walter4) Examining remnants of organic material in Earth’s oldest sedimentary rocks is an essential part of tracing the origins of life on our plant and important for developing techniques to search for traces of life on other plants. Accordingly, carbonaceous materials in Early Archaean (3.2-3.5 billion year old) sedimentary rocks are coming under scrutiny to determine whether evidence of biology can be elucidated. The Archaean Pilbara Craton, Australia, is the best place in the world to study the early Earth – it has a geological history from >3.5 through to 2.4 billion years old, preserved at low metamorphic grade with low strain rocks that contain Earth’s oldest hydrothermal systems. The aim of this project is to elucidate the macromolecular structure of the carbonaceous materials in these rocks and hence determine any molecular biomarkers which may provide evidence for either a biological or and non-biological origin of these materials. The research so far has resulted in 5 papers including one published in Nature in 2006 (ref 1). 2 3 UC Riverside, USA MIT, USA NASA, USA Macquarie University, Australia WHOI, USA 6 University of Liege, Belgium 7 Harvard University, USA 8 UNSW, Australia 4 5 Selected Publications A New Approach in Deciphering Early Protist Paleobiology and Evolution (Olcott , Javaux , Knoll7) 5 6 Acritarchs are organic walled microfossils of unknown biological affinities. They are conventionally interpreted as algal cysts but most probably include a larger range of organisms such as prokaryotic sheaths, heterotroph protists or even parts of multicellular beings. Biologists easily differentiate between prokaryotic and eukaryotic organisms using molecular and cell biology, but these characters rarely survive fossilization. Identifying the biological affinities of these microscopic organisms will clarify Proterozoic (2.5 Ga to 5.5 Ma) microbial paleobiology. It will also contribute to phylogenetic reconstructions, and improve our understanding of early evolutionary mechanisms and patterns, and the early interactions between environment and life. New approaches are necessary to elucidate their paleobiology. Single microfossils are being investigated by Raman and infrared spectroscopy. The Role of Microbes and Organic Matter in the Formation of Ore Deposits (Walter4) The main aims of this project were to determine the palaeo-temperature of McArthur Pb-Zn-Ag orebody, characterise organic matter from orebody and host sediments, and determine the biological affinities of microfossils in the surrounding sediments. The palaeo-temperatures represented by the ore fluid pathway are poorly understood. However, our studies using Raman spectroscopy of organic matter associated with the ore indicates a palaeo-temperature of the mineralizing fluids of 120-220ºC. This has significant impact on mineral exploration models for this style of deposit. The major issue was to resolve whether the ore sulfides formed within the sediment pile or in the overlying water body. Our results 1. Allwood, AC, Walter, MR, Kamber, BS, Marshall, CP and Burch, IW. Stromatolite reef from early Archaean era of Australia. Nature, 441, 714-718, 2006. 2. Marshall, CP, Love, GD, Snape, CE, Hill, AC, Allwood, AC, Walter, MR, Van Kranendonk, MJ, Bowden, SA, Sylva, SP and Summons, RE. Structural characterization of kerogen in 3.4 Ga Archaean cherts from the Pilbara Craton, Western Australia. Precambrian Research, 155, 1-23, 2007. 3. Allwood, AC, Walter, MR and Marshall, CP. Raman spectroscopy reveals thermal palaeoenvironments of c.3.5 billion-year-old organic matter. Vibrational Spectroscopy, 41, 190-197, 2006 4. Marshall, CP, Carter, EA, Leuko, S and Javaux, EJ. Vibrational spectroscopy of extant and fossil microbes: Relevance for the astrobiological exploration of Mars. Vibrational Spectroscopy, 41, 182-189, 2006. 72 School of Chemistry Dr Malcolm D McLeod Room 517 School of Chemistry, F11 Telephone: +61 2 9351 5877 Facsimile: +61 2 9351 3329 Email: [email protected] http://www.chem.usyd.edu.au/about/staff_mcleod.html organic synthesis Our research interests include the development of new synthetic methods and the chemical synthesis of biologically active natural products and their analogues. Enantioselective Total Synthesis of the Cytotoxic Macrolide (–)-Dactylolide (Louis, Hungerford) Annual Research Report 73 Chemistry and Biology of Nicotinic Acetylcholine Receptors (nAChRs) (Halliday, Lin, Collins*) Nicotinic acetylcholine receptor (nAChR) chemistry and biology is currently of enormous interest in the field of drug development. The receptors have been implicated as playing a role in conditions such as epilepsy, Alzheimer’s disease and schizophrenia. However, few compounds differentiate between the different nAChR subtypes. Methyllycaconitine is a selective and potent α7 nAChR antagonist but the size and complexity of this natural product render it unsuitable as a therapeutic agent in its own right. We have recently developed new methods for the double-Mannich annulation reaction that increase the yield and decrease the number of steps needed to access analogue structures (Ref 3). Testing of our analogues completed has shown that they act as antagonists at a number of different nAChR subtypes but they have different modes of action at each receptor subtype (Ref 4). Current research aims to improve the activity and selectivity of the class of ligands under investigation by varying their structure. The project was awarded an ARC Discovery Project Grant in 2005. Synthesis and Analysis of Anabolic Steroid Metabolites (Bain, Hungerford, Pu, Wilkinson, McKinney*, Stenhouse*) This project is conducted in collaboration with the Australian Racing Forensic Laboratories located in Randwick and aims to develop new methods for illicit drug detection in thoroughbred and harness and greyhound racing. The project was awarded two ARC Linkage Project Grants in 2002 and research is currently focused on three main areas: 1) the development of high throughput assays based on immunoassays for the rapid preliminary screening of race day samples (Ref 5); 2) the chemical synthesis of phase II metabolites and the development of direct methods for their detection (Ref 6) , and; 3) new methods that use genetically engineered enzymes called glycosynthases for the synthesis of steroid glucuronide conjugates. We reported enantioselective total synthesis of the cytotoxic marine natural product (–)-dactylolide in Organic Letters in early 2006 (Ref 1). This complex natural product contains a 20-membered macrocyclic ring with a high degree of unsaturation and a complex array of stereochemistry. A notable feature of the synthesis is a sequence of substrate controlled reactions to efficiently introduce the remote C19-stereochemistry present in the target. This allows for the absolute stereochemistry of the molecule to be derived in one catalytic asymmetric step using a hetero-Diels-Alder reaction. The total synthesis was published. Total Synthesis of the Microsclerodermins: Anti-fungal Cyclic Peptides (Stewart, Shuter, Hutton*) Our aim is to discover new anti-fungal treatments for drug-resistant pathogenic fungal infections based on the microsclerodermin family of natural products. A synthesis route is required as the small quantity available from the natural environment hampers the development of anti-fungal agents from this natural product. Innovative synthetic methods are being developed to prepare large quantities of microsclerodermins and related compounds for biological testing, thereby furthering the development of this promising class of anti-fungal drugs. The project was awarded an ARC Discovery Project in 2003 (with Dr Craig Hutton). The development of substrate controlled Asymmetric Aminohydroxylation (AA) and Asymmetric Dihydroxylation (AD) reactions has led to the synthesis of unusual amino acid components of microsclerodermins such as the pyrrolidinone, APTO and GABOB (Ref 2). Current work is directed to remaining unusual amino acid components of the target such as the chlorotryptophan residue and assembly of the macrocycle. Selected Publications 1. Louis, I, Hungerford, NL, Humphries, EJ and McLeod, MD. Enantioselective total synthesis of (–)-dactylolide. Org. Lett., 8, 11171120, 2006. 2. Harding, M, Bodkin, JA Hutton, CA and McLeod, MD. Substrate control in the asymmetric aminohydroxylation of monosubstituted alkenes: the enantioselective synthesis of GABOB and homoserine derivatives. Synlett, 18, 2829-2831, 2005. 3 Halliday, JI, Chebib, M, Turner, P, McLeod, MD Double-Mannich annulation of cyclic ketones using N,N-bis(ethoxymethyl)alky lamine reagents. Org. Lett., 8, 3399-3401, 2006. 4. Barker, D, Lin, DH-S, Carland, JE, Chu, CP-Y, Chebib, M, Brimble, MA, Savage, GP and McLeod, MD. Methyllycaconitine analogues have mixed antagonist effects at nicotinic acetylcholine receptors. Bioorg. Med. Chem., 13, 4565-4575, 2005. 5. Hungerford, NL, Sortais, B, Smart, CG, McKinney, AR, Ridley, DD, Stenhouse, AM, Suann, CJ, Munn, KJ, Sillence, MN and McLeod, MD. Analysis of anabolic steroids in the horse: development of a generic ELISA for the screening of 17α-alkyl anabolic steroid metabolites. J. Steroid Biochem. Mol. Biol., 96, 317-334, 2005. 6 Hungerford, NL, McKinney, AR, Stenhouse, AM, McLeod, MD. Selective manipulation of steroid hydroxyl groups with boronate esters: Efficient access to antigenic C-3 linked steroid-protein conjugates and steroid sulfate standards for drug detection. Org. Biomol. Chem., 4, 3951-3959, 2006. 74 School of Chemistry Annual Research Report 75 Dr Damian Moran Room 209a School of Chemistry, F11 Telephone: +61 2 9351 5358 Facsimile: +61 2 9351 3329 Email: [email protected] http://www.chem.usyd.edu.au/~dmoran/ computational predictions concerning structure, stability and mechanism The application of modern theoretical methods now provides a “green” alternative to the laboratory for the study of chemistry. While traditionally limited to relatively small molecules, the present explosive developments in computer hardware have guaranteed that the frontiers of computational chemistry are rapidly expanding. My research involves the application of computational chemistry to problems of chemical interest, including predictions concerning structure, stability and reaction mechanism. Recent research highlights include the discovery that several well established and commonly employed computational-chemistry methods incorrectly predict that planar aromatic molecules are bent (J. Am. Chem. Soc. 2006, 128, 9342). The impact of this discovery is demonstrated by noting that it featured in the highlights section of Science (2006, 313, 149) and of Nachrichten aus der Chemie (2006, 54, 842). Peptide Radical Rearrangements As part of a major collaboration, a broad computational investigation of neutral polypeptide radicals and their rearrangements is being undertaken. My recent efforts have included an investigation of the mass spectrometric fragmentation patterns of complexes between sodium ions and neutral peptide radicals. The structures of these cation complexes are complicated, which in turn convolutes interpretations concerning their fragmentation mechanisms. In this regard, computations have proven to be extremely helpful, particularly with respect to learning about the barriers to intramolecular radical rearrangement prior to fragmentation (Chem. Commun. 2006, 4233). Selected Publications 1. Hemelsoet, K, Van Speybroeck, V, Moran, D, Marin, GB, Radom, L and Waroquier, M. Thermochemistry and kinetics of hydrogen abstraction by methyl radical from polycyclic aromatic hydrocarbons. J. Phys. Chem. A, 110, 13624–13631, 2006. 2. Moran, D, Jacob, R, Wood, GPF, Coote, ML, Davies, MJ, J. O’Hair, RA, Easton, CJ and Radom, L. Rearrangements in model peptide-type radicals via intramolecular hydrogen-atom transfer. Helv. Chim. Acta, 89, 2254–2272, 2006. 3. Wee, S, Mortimer, A, Moran, D, Wright, A, Barlow, CK, J. O’Hair, RA, Radom, L and Easton, CJ. Gas-phase regiocontrolled generation of charged amino acid and peptide radicals. Chem. Commun., 4233–4235, 2006. 4. Moran, D, Simmonett, AC, Leach, FE, Allen, WD, Schleyer, PvR and Schaefer, HF. Popular theoretical methods predict benzene and arenes to be non-planar. J. Am. Chem. Soc., 128, 9342–9343, 2006. 5. Hemelsoet, K, Moran, D, Van Speybroeck, V, Waroquier, M and Radom, L. An assessment of theoretical procedures for predicting the thermochemistry and kinetics of hydrogen abstraction by methyl radical from benzene. J. Phys. Chem. A, 110, 8942–8951, 2006. 6. Corral, I, Mó, O, Yáñez, M, Salpin, JY, Tortajada, J, Moran, D and Radom, L. An experimental and theoretical investigation of gas-phase reactions of Ca2+ with glycine. Chemistry - Eur. J. 12, 6787–6796, 2006. 7. Barlow, CK, Moran, D, Radom, L, McFadyen, WD and O’Hair, RAJ. Metal-mediated formation of gas-phase amino acid radical cations. J. Phys. Chem. A, 110, 8304–8315, 2006. 8. Goh, SW, Buckley, AN, Lamb, RN, Rosenberg, RA and Moran, D. The oxidation states of copper and iron in mineral sulfides, and the oxides formed on initial exposure of these sulfides to air. Geochim. Cosmochim. Acta, 70, 2210–2228, 2006. 76 School of Chemistry Dr Klaas Nauta Room 315 School of Chemistry, F11 Telephone: +61 2 9351 3777 Facsimile: +61 2 9351 3329 Email: [email protected] superfluid helium droplets Helium nanodroplet spectroscopy is a new and exciting field in physical chemistry. Helium droplets are formed by expanding high pressure helium at low temperatures into vacuum. This produces a beam of helium droplets with a size range of several hundred to several hundreds of thousands atoms or, on average, a few nanometers in diameter. They are extremely small, significantly smaller than, e.g., atmospheric aerosoles (micrometers), but still large enough to capture and dissolve several molecular species. It is the ease with which the droplets can be ‘doped’ with molecules that makes them a very useful experimental tool. Dopant species are introduced by passing the droplets through a small scattering region where a slightly elevated background pressure of the compound of interest is maintained. The beam of doped helium droplets can then be probed via laser spectroscopy and mass spectrometry. Annual Research Report 77 Unique Stuctures Because individual molecules are each dissolved in their own helium droplet, from which they cannot escape, helium droplets have sometimes been termed ‘nanoscales laboratories’. Where more than one molecule dissolves in a single droplet, the dopant species combine to form a van der Waals complex whose structure is governed by relatively long range forces, e.g. dipole-dipole interaction. The internal temperature of the droplets, and hence the dopant molecules, has been measured at 0.37+/-0.03 K. At these temperatures, even small barriers on the potential energy surface can be enough to prevent rearrangement of one structural isomer into another. Studies have shown that unique van der Waals complexes are indeed formed inside helium droplets and often the resulting structures closely resemble the structural motif of the corresponding bulk (liquid or solid) phases of the dopant species. An example is the observation of a cyclic water hexamer, the structural motif of plain water ice and an isomer of water6 that is not stable by itself in the gas phase. Reactions at Zero Kelvin Well, not exactly 0 K, but close enough. The extremely low temperature inside helium droplets and the facility with which they can be doped with a wide variety of species opens up the possibility to capture and stabilise molecular complexes that in another medium, or in the gas phase, at higher temperatures, would not be stable. A famous example is the dimer of the OH radical which theory predicts should be stable but has yet eluded experimental observation. Helium droplets might be used to bring two cold (0.37 K) OH radicals together to form a weakly bound, metastable complex that cannot react (too cold!) without being externally triggered. Once formed, the complex may be excited via laser radiation to give it just enough energy to overcome the barrier to rearrangement, and reaction. Many radicalradical and radical-molecule reactions exist in nature and often these are very hard to study due to the transient nature of the intermediate complexes. Spectroscopy of Molecular Ions Over the past year the helium droplet apparatus was fitted with a time-of-flight mass spectrometer. The spectrometer was successfully tested by measuring the gas phase spectra of naphthalene-argon clusters, incidentally revealing the correct gas phase structure of naphthalene dimer for the first time. It is our goal, as part of the joint astro-chemistry project in the laser spectroscopy group, to use the combined helium-droplet/mass-spectrometry apparatus to measure the optical spectra of large molecular ions trapped in helium droplets. Molecular ions, e.g. PAH cations, have been frequently postulated as one of many possible carriers of absorption bands in the interstellar medium, but it has proven exceedingly difficult to measure their spectra in the laboratory. Helium droplet spectroscopy provides an elegant way of bypassing many of the problems associated with measuring the spectra of molecular cations. Selected Publications Superfluid Dynamics One unique property of liquid helium droplets is that they are superfluid. A result of this superfluidity is that a molecular dopant can rotate freely inside the helium. Although the helium will attempt to move with the molecule (and thus affect its moment of inertia), no energy is exchanged between the dopant molecule and the surrounding solvent. The motion is non-dissipative as opposed to motion in a classical liquid which is rapidly frictionally dampened. Studying the spectroscopy of various molecular species in helium droplets can teach us much about the nature of superfluidity at the microscopic level and how it interacts with and is affected by the presence of the molecule. 1. Nauta, K and Miller, RE. The spectroscopy of molecules and unique clusters in superfluid helium droplets. Campargue, R (editor), Springer-Verlag, Berlin, Atomic and Molecular Beams, 775-792, 2001. 2. Scoles, G and Lehmann, KK. Molecular spectroscopy - Nanomatrices are cool. Science, 287, 2429, 2000. 3. Nauta, K and Miller, RE. Nonequilibrium self-assembly of long chains of polar molecules in superfluid helium. Science, 283, 1895, 1999. 4. Nauta, K and Miller, RE. Formation of cyclic water hexamer in liquid helium: The smallest piece of ice. Science, 287, 293, 2000. 5. Grebenev, S, Toennies, JP and Vilesov, AF. Superfluidity within a small helium-4 cluster: The microscopic Andronikashvili experiment. Science, 279, 2083, 1998. 6. Lugovoj, E, Toennies, JP and Vilesov, A. Manipulating and enhancing chemical reactions in helium droplets. J. Chem. Phys, 112, 8217, 2000. 78 School of Chemistry Professor Leo Radom, FAA Room 309 School of Chemistry, F11 Telephone: +61 2 9351 2733 Facsimile: +61 2 9351 3329 Email: [email protected] http://www.chem.usyd.edu.au/about/staff_radom.html computational quantum chemistry Chemistry is traditionally an experimental science. However, recent advances in computer technology and the development of highly efficient computer algorithms have opened the way for a viable alternative approach to chemistry: chemistry by computer. We use such computer calculations, based on the laws of quantum mechanics, to determine the structures of molecules and to help understand how molecules react with one another. Enzyme-Catalysed Reactions (Sandala, Durbeej, Smith§, Coote†, Marsh‡, Golding‡) Vitamin B12 is one of nature’s essential vitamins. We have used ab initio quantum chemistry calculations to model reactions mediated by coenzyme B12 (also known as adenosylcobalamin or AdoCbl). Although these reactions have been extensively studied experimentally, there is certainly no consensus as to how they Figure 1 proceed. We have proposed mechanisms involving partial-protontransfer (donation or acceptance) provided by enzymatic hydrogen bonding. Supporting evidence for our proposals has come from site-directed mutagenesis experiments. These and other recent examples provide strong encouragement for the use of such computer calculations in a predictive manner in the study of enzyme reactions. Our most recent work has been concerned with suicide inactivation, involving the inactivation of B12 enzymes by substrate analogues. We have found that the inactivation is associated with the formation of highly stable radicals, impeding the regeneration of Ado• radicals and leading to disruption of the catalytic cycle (see Figure 1). Annual Research Report Development of Improved Theoretical Procedures (Wood, Merrick, Moran, Petersson‡) The ability to predict reliable thermochemistry represents a very important application of ab initio quantum chemistry. We have recently been designing and assessing methods that are suited for predicting accurate thermochemistry for free radicals because these represent particular challenges for theoretical investigation. Our latest work has been concerned with developing an improved procedure for examining radicals within the complete-basis-set (CBS) formalism, designated ROCBS-QB3. In separate work, we have been deriving scale factors that may be used to transform calculated harmonic vibrational frequencies to useful thermodynamic quantities for a wide variety of theoretical procedures. Interaction of Metal Ions With Biological Systems (Moran, Corral§, Yanez§, Mo§, Tortajada‡) Metal ions are of great importance in biological function. We have embarked on a broad-based theoretical study to probe the interaction of metal ions with prototypical biological molecules. Our initial investigations have focussed on the interaction of calcium dications with simple model systems in order to establish suitable theoretical procedures that can be applied to larger molecules. Calculations on the interaction of calcium dication with urea and glycine have been carried out in parallel with experimental mass spectrometric studies, and used to help interpret the observed mass spectrometric fragmentation patterns. Hydrogenation (Chan, Zhong, Miller, Smith§) Hydrogenation is a very important process in chemical systems. It is generally brought about by transition metal or heavy metal catalysts. However, in recent years it has been demonstrated that catalytic hydrogenation can also be accomplished in the absence of such metals. We are using theory to try to design systems in which metal-free hydrogenations can occur with low energy requirements. Our initial studies have involved the acid- and base-catalysed hydrogenation of ethene and other doubly-bonded systems, as well as catalysis by zeolites. As part of such studies, we have designed a new class of zeolites that show the potential to transform carbon dioxide to methanol at a low energy cost. In separate work on the hydrogenation of aromatic hydrocarbons, we have found examples where kinetics do not follow thermodynamics, e.g., in the production of 1,4- and 1,3-cyclohexadiene from benzene (see Figure 2). In the area of transfer hydrogenation, we have found that for the prototype reaction of ethane with ethene a concerted pathway is preferred over a stepwise pathway that involves Figure 2 free radicals. § † Fundamentals of Free Radical Chemistry (Menon, Ivanic, Wood, Moran, Taylor, Sandala, Durbeej, Hemelsoet§, Coote†, Easton†, Henry†, Van Speybroeck‡, Warochier‡) Radicals are ubiquitous in chemistry, biology, and polymer science. Because they are reactive species, they are often difficult to study experimentally and therefore theory has a potentially useful role to play in their characterisation. We have been using theory to determine radical stabilisation energies, with the important aim of seeing how individual substituents stabilise or destabilise a radical centre. We have also been examining the details of addition, abstraction and rearrangement reactions of radicals. These are very important in biological chemistry and polymer chemistry. We have been particularly interested in hydrogen-atom abstraction by the methyl radical from polycyclic aromatic hydrocarbons. Finally, in the context of the radical abstraction reactions, we have been examining quantum mechanical tunneling and isotope effects. Peptide Radical Chemistry (Wood, Moran, Barlow§, Wee§, Gordon§, Jacob†, Coote†, Easton†, Rauk‡, Davies‡, O’Hair‡) An understanding of the oxidation of proteins by free radicals is of great importance because of its implication in a number of human disorders such as Alzheimer’s disease, atherosclerosis, and diabetes, as well as aging. We have been using high-level quantum chemistry calculations to address the problem. Initial targets have included the cleavage of the peptide backbone following radical formation, and migration of the radical site within the peptide, both with and without attachment to a metal ion. We have also examined solvation effects. 79 ‡ Current or former Visiting Scholar/Professor in the School of Chemistry. Current/former member of Research School of Chemistry, ANU. Coworker not associated with University of Sydney or ANU. Selected Publications 1. Miller, DJ, Smith, DM, Chan, B and Radom, L. Transfer hydrogenation between ethane and ethene: A critical assessment of theoretical procedures. Mol. Phys., 104, 777–794, 2006. 2. Sandala, GM, Smith, DM, Coote, ML, Golding, BT and Radom, L. Insights into the hydrogen-abstraction reactions of diol dehydratase: Relevance to the catalytic mechanism and suicide inactivation. J. Am. Chem. Soc., 128, 3433–3444 (2006). 3. Chan, B and Radom, L. Design of effective zeolite catalysts for the complete hydrogenation of CO2. J. Am. Chem. Soc., 128, 5322–5323, 2006. 4. Moran, D, Jacob, R, Wood, GPF, Coote, ML, Davies, MJ, O’Hair, RAJ, Easton, CJ and Radom, L. Rearrangements in model peptide-type radicals via intramolecular hydrogen-atom transfer. Helv. Chim. Acta, 89, 2254–2272, 2006. 5. Wood, GPF, Radom, L, Petersson, GA, Barnes, EC, Frisch, MJ and Montgomery, JA. A restricted-open-shell complete-basis-set model chemistry. J. Chem. Phys., 125, 094106-1–094106-16, 2006. 6. Wood, GPF, Easton, CJ, Rauk, A, Davies, MJ and Radom, L. The effect of side chains on competing pathways for b-scission reactions of peptide-backbone alkoxyl radicals. J. Phys. Chem. A, 110, 10316–10323, 2006. 7. Hemelsoet, K, Van Speybroeck, V, Moran, D, Marin, GB, Radom, L and Waroquier, M. Thermochemistry and kinetics of hydrogen abstraction by methyl radical from polycyclic aromatic hydrocarbons. J. Phys. Chem. A, 110, 13624–13631, 2006. 8. Wee, S, Mortimer, A, Moran, D, Wright, A, Barlow, CK, O’Hair, RAJ, Radom, L, and Easton, CJ. Gas-phase regiocontrolled generation of charged amino acid and peptide radicals. Chem. Comm., 4233–4235, 2006. 9. Sandala, GM, Smith, DM and Radom, L. In search of radical intermediates in the reactions catalyzed by lysine 2,3-aminomutase and lysine 5,6-aminomutase. J. Am. Chem. Soc., 128, 16004–16005, 2006. 80 School of Chemistry Professor Jeffrey R Reimers Room 546 School of Chemistry, F11 Telephone: +61 2 9351 4417 Facsimile: +61 2 9351 3329 Email: [email protected] http://www.chem.usyd.edu.au/about/staff_reimers.html Annual Research Report 81 important as it provided the first observed direct molecular dependence of the current; it also allows for understanding the effects of heating of practical devices. A general theory has been developed7 and implemented in the circuit simulator fREEDA that allows molecular components to be simulated in solid-state devices of the complexity of say the Pentium® processor. A major research program funded by INTEL is also in progress, concerned with the development of a molecular memory for computers. Fundamentals (Cai) Fundamental research is performed in areas such as solvation, quantum chemistry, and quantum mechanics in order to determine effective means for dealing with both simple and complex chemical systems. In 2006 two Special Issues of the Journal Chemical Physics were produced highlighting electron transfer in chemistry, biology, and nanotechnology5-6. An explanation was also provided3 for the nature of the N-band absorptions of porphyrins and chlorophylls. While the spectroscopy of these molecules is usually dominated by the typically lower energy Q and Soret ban systems, we identify the nature of the N bands as charge-transfer states, see figure. These are shown to interact strongly with their environment, including chemical substituents, having profound effects for oligoporphyrin-based molecular wires. This work also established the first efficient a priori computational scheme capable of describing the excited states of porphyrins and chlorophylls. molecular electronics, Photosynthesis Photosynthesis and Photovoltaics (Canfield, Hush, Crossley) The conversion of optical to chemical energy by plants is central to most forms of life on this planet. We have computational quantum chemistry2 to optimize the structure of the 150000-atom Photosystem-I from green plants and used this to form a model for optical energy flow from the antenna pigments to the “special pair” responsible for the conversion of optical to electrical energy. One third of this optimized structure is shown in the figure. In addition, the actual solar-energy conversion process in purple bacteria has been studied9 in great detailed through prediction of the Stark spectra of a range of reaction centres produced and studied experimentally by Boxer (Stanford). This shows how to control the output voltage both in natural photosynthesis and in organic photovoltaic devices. Molecular Electronics (Solomon, Cafe, Chin, Larson, Wang, Ren, Hush, Crossley) A rather large research field has opened in the area of molecular electronics, the exploitation of the electrical conductivity properties of single molecules, with much research now performed by companies such as IBM, HP, Bell Labs, and Hitachi. We have been involved in the development of the field since its first conception. During 2006 we determined the mechanism for the physisorption of aromatic molecule on noble metal surfaces 8 and assembled a comprehensive review1 of the cycloaddition reactions of alkenes with the silicon (100) surface. A major theory was presented4,10-13 to explain the recently observed Inelastic Electron Conduction Spectroscopy of molecules such as alkaendithiols chemisorbed to span two gold electrodes. As shown in the simulated spectra presented in the figure, this technique allows the molecular vibrational spectrum to be measured from the second derivative of the current (I) passing through the molecule as a function of bias voltage (V). This is Selected Publications 1. Bilic, A, Reimers, JR and Hush, NS. Functionalization of semiconductor surfaces by organic layers: Concerted cycloaddition versus stepwise free-radical reaction mechanisms. Properties of Single Organic Molecules on Crystal Surfaces, 333-360, 2006. 2. Canfield, P, Dahlbom, MG, Hush, NS and Reimers, JR. Density-functional geometry optimization of the 150 000-atom photosystemI trimer. Journal of Chemical Physics, 124, 24301, 2006. 3. Cai, Z-L, Crossley, MJ, Reimers, JR, Kobayashi, R and Amos, RD. Density functional theory for charge transfer: The nature of the N-bands of porphyrins and chlorophylls revealed through CAM-B3LYP, CASPT2, and SAC-CI calculations. Journal of Physical Chemistry B, 110, 15624-15632, 2006. 4. Solomon, GC, Gagliardi, A, Pecchia, A, Frauenheim, T, Di Carlo, A, Reimers, JR and Hush, NS. Understanding the inelastic electron-tunneling spectra of alkanedithiols on gold. Journal of Chemical Physics, 124, 094704, 2006. 5. Reimers, JR, Ulstrup, J, Meyer Thomas, J and Solomon, GC. Special Issue: The molecules and methods of chemical biochemical, and nanoscale electron transfer – Part 2 in honour of Noel S. Hush on his 80th birthday. Chemical Physics, 324, 2006. 6. Reimers, JR, Ulstrup, J, Meyer Thomas, J and Solomon, GC. Special Issue: The molecules and methods of chemical biochemical, and nanoscale electron transfer – Part 2 in honour of Noel S. Hush on his 80th birthday. Chemical Physics, 326, 2006. 7. Kriplani, NM, Nackashi, DP, Amsinck, CJ, Di Spigna, NH, Steer, MB, Franzon, PD, Rick, RL, Solomon, GC and Reimers, JR. Physically based molecular device model in a transient circuit simulator. Chem. Phys., 326, 188, 2006. 8. Bilic, A, Reimers, JR, Hush, NS, Hoft, RC and Ford, MJ. Adsorption of benzene on copper, silver, and gold surfaces. Journal of Chemical Theory and Computation, 2, 1093-1105, 2006. 9. Kanchanawong, P, Dahlbom, MG, Treynor, TP, Reimers, JR, Hush, NS and Boxer, SG. Charge delocalization in the special-pair radical cation of mutant reaction centers of Rhodobacter sphaeroides from stark spectra and nonadiabatic spectral simulations. Journal of Physical Chemistry B, 110, 18688-18702, 2006. 10. Solomon, GC, Gagliardi, A, Pecchia, A, Frauenheim, T, Di Carlo, A, Reimers, JR and Hush, NS. Molecular origins of conduction channels observed in shot-noise measurements. Nano Letters, 6, 2431-2437, 2006. 11. Solomon, GC, Gagliardi, A, Pecchis, A, Frauenheim, T, Di Carlo, A, Reimers, JR and Hush, NS. The symmetry of single-molecule conduction. Journal of Chemical Physics, 125, 184702, 2006. 12. Pecchia, A, Gagliardi, A, Solomon, G, Di Carlo, A, Frauenheim, T and Reimers, JR. Incoherent tunnelling and heat dissipation in moecular bridges. J. Phys. Conf. Ser., 2006. 13. Gagliardi, A, Solomon, G, Pecchia, A, Di Carlo, A, Frauenheim, T, Reimers, JR and Hush, NS. Simulations of inelastic tunnelling in molecular bridges. In Nonequilibrium Carrier Dynamics in Semiconductors (Eds: Saraniti, M and Ravaioli, U), Springer-Verlag: Berlin, 110, 183-186, 2006. 82 School of Chemistry Dr Louis M Rendina Room 518 School of Chemistry, F11 Telephone: +61 2 9351 4781 Facsimile: +61 2 9351 3329 Email: [email protected] http://www.chem.usyd.edu.au/about/staff_rendina.html synthesis & bio-coordination chemistry Platinum-Carborane Complexes as New Agents for Boron Neutron Capture Therapy (Ching, Coderre*, Crossley, Fisher) The principal goal of this research program is to expand the clinical efficacies of platinum chemotherapy and radiotherapy by coupling the potent DNA-binding characteristics of certain platinum compounds with the remarkable neutron capture properties of the non-radioactive 10B nucleus that have been exploited in an experimental cancer treatment known as Boron Neutron Capture Therapy (BNCT). BNCT is currently undergoing Phase I/II clinical trials in several countries for the treatment of the brain tumour glioblastoma multiforme and malignant melanoma. The therapy utilizes 10B-containing drugs and thermal neutrons of low kinetic energy (< 0.025 eV), although epithermal neutrons allow for deeper tissue penetration. The very large, effective nuclear cross-section of the 10B nucleus (3837 barns, natural abundance = 19.8%) makes it highly amenable to the neutron capture process. The major (94 %) reaction is shown in eq. 1: B 10 + 1 n → [11B*] → He2+ 4 + Li+ 7 + γ + 2.4 MeV (eq. 1) The primary nuclear fission products that are produced in the neutron capture reactions have a high rate of linear energy transfer and they cover a short range (ca. 10 µm, or one cell diameter). As a result, the immense amount of energy derived from the nuclear reaction is dissipated in a very small volume and the selective destruction of tumour cells becomes feasible with this type of therapy. 10B compounds that are localised near key cellular components such as chromosomal DNA cause maximum cell damage in the presence of thermal neutrons. The proof-of-principle for the synthesis, DNAbinding, and tumour cell uptake of the archetypal Pt-carborane complexes has already been established in our laboratory and the complexes represent two new classes of DNA-binding agents for potential use in BNCT. We have investigated the deboronation reactions of closo-carborane derivatives to afford the corresponding anionic nido-carborane species, which in some cases easily react with acetone to afford boron-rich dithioether carborane ligands containing 18 boron atoms. We have also prepared novel dodecaborate(12) derivatives, e.g. [B12H11O(CH2)4SH]2–, as these should possess significantly enhanced aqueous solubility and boron content compared to the corresponding closo-carboranes analogues. Finally, we have prepared simple boronic acid derivatives of platinum(II) metallointercalator complexes. These species readily undergo acid-base chemistry and we have commenced studies into their sugar-boronate ester derivatives which should afford hydrophilic complexes possessing interesting biological properties. *Department of Nuclear Science and Engineering, MIT. Tumour-Targeted Boronated Phosphonium Salts as a New Class of Agents for Boron Neutron Capture Therapy (Ioppolo) It has been previously shown that phosphonium salts including triphenylmethylphosphonium (TPMP) represent a promising class of delocalised lipophilic cations (DLCs) for use in tumour targeting and imaging. It is known that the tumour selectivity and retention of TPMP in animal models is at least one order of magnitude greater than for clinical agents currently used in BNCT. The incorporation of boron into DLCs such as TPMP would potentially result in the selective delivery of this nucleus to the tumour site, notably by exploiting the key differences in the mitochondrial membrane potential between cancerous and healthy cells. This is a highly significant innovation in the area of BNCT and the expected outcomes include the development of new agents for the treatment of high-grade gliomas. We have recently Annual Research Report 83 prepared the first examples of boronated arylphosphonium salts. These compounds exhibit exquisite uptake in SF268 human glioblastoma cells in vitro. In some cases, e.g. when 1,2-carborane is used, the phosphonium salt undergoes facile deboronation in polar solution to afford the corresponding zwitterionic species containing a nido-carborane cage (Fig. 1) and may thus be considered to be a “masked” phosphonium salt. This work was recently the subject of a Provisional Patent (Ref. No. 2007900804) filed by The University of Sydney. Boronated RGD Cyclic Peptides as a New Class of Tumour-Specific Agents for Boron Neutron Capture Therapy (Jolliffe, MacKay, Ziolkowski) The primary goal of this project is to design and synthesise a series of boronated cyclic peptides that will have the capacity to target over-expressed integrin proteins involved Figure 1 in tumour angiogenesis and metastasis. In this project, there exists the potential of delivering boron selectively to the tumour site and greatly improving the efficacy of BNCT. Recent work has focussed on the synthesis of boronic acid derivatives of cyclic RGD (Arg-Gly-Asp) peptides, and the syntheses of the first prototype compounds are now close to completion. We have also established comprehensive in vitro cytotoxicity assays involving a series of tumour cell lines. DNA Nanoshuttles (Harding¶, Mulcahy, Saccavini, Schilter) A key feature that characterises the structure of toroidal DNA-binding proteins such as the DNA sliding clamp is the central hole (~35 Å) which is large enough to accommodate double-helical nucleic acid with little steric hindrance for B-DNA (~20 Å diameter). In general, the DNA-protein interaction is purely topological, and it is greatly stabilised by powerful electrostatic interactions between the polyanionic phosphodiester backbone of DNA and a region of high positive potential that surrounds the inner surface of the toroid. In this research program, we have sought to answer whether linear DNA can thread nanoscale cationic macrocycles of platinum that we have termed DNA Nanoshuttles. The interaction of nanoscale metal complexes with DNA is unprecedented and it would represent a significant advance in the field of metal-DNA chemistry. Recent work has focussed on (i) the synthesis of highly water-soluble N-donor ligands for incorporation into molecular squares and polygons and (ii) the generation of a cationic macrocycle with a cavity size of ca. 3 nm by the reaction of the labile precursor complexes [Pt(bpy)(NO3)2] or [Pd(bpy)(NO3)2] and PEG diamine ligands. ESI-MS analysis of the platinum(II) product revealed the presence of ions distributions centred at m/z = 1310, 1247 and 624; these are assigned to the ions [M – NO3–]+, [M – 2NO3– – H+]+ and [M – 2NO3–]2+, respectively. With the corresponding palladium(II) precursor, the unique species was formed in almost quantitative yield and the ESI spectra featured two prominent isotopic distributions centred at m/z = 1222 and 579. The envelopes are consistent with ions incorporating one palladium(II) ion and correspond to [M – NO3–]+ and [M – 2NO3–]2+, respectively. Complex has also been analysed by ESI-FT-ICR-MS and these high resolution results are in complete accord with the low-resolution spectra. Importantly, there is no evidence of higher nuclearity species in either case, e.g. [2+2] species or catenanes. Importantly, this reaction was found to be completely reproducible and the complexes are very water-soluble. An analogous organo-soluble species containing a chelating phosphine ligand was also prepared and fully characterized. We are now in a strong position to commence comprehensive DNA-binding studies with selected complexes in 2007. ¶ School of Chemistry, UNSW. Selected Publications 1. Ioppolo, JA, Clegg, JK and Rendina, LM. Dicarba-closo-dodecaborane(12) derivatives of phosphonium salts: Formation of nidocarborane phosphonium zwitterions. Dalton Trans., 1982-1985, 2007. 2. Ching, HYV, Clegg, JK and Rendina, LM. Synthesis and preliminary DNA-binding studies of diimineplatinum(II) complexes containing 3- or 4-pyridineboronic acid. Dalton Trans., 2121, 2007. 3. Crossley, EL, Ziolkowski, EJ, Coderre, JA and Rendina, LM. Boronated DNA-binding compounds as potential agents for boron neutron capture therapy. Mini Rev. Med. Chem., 7, 303-313, 2007. 4. Lee, CKY, Groneman, JL, Turner, P, Rendina, LM and Harding, MM. Synthesis and X-Ray crystallographic analysis of chiral pyridyl substituted carbocyclic molecular clefts. Tetrahedron, 62, 4870-4878, 2006, 84 School of Chemistry Dr Siegbert A Schmid Room 223 School of Chemistry, F11 Telephone: +61 2 9351 4196 Facsimile: +61 2 9351 3329 Email: [email protected] http://www.chem.usyd.edu.au/about/staff_schmid.html INORGANIC SOLID STATE CHEMISTRY and CHEMISTRY EDUCATION Research in my group focuses on two major areas – Inorganic Solid State Chemistry and Education in Chemistry. Research projects in the former area encompass a wide range of both synthetic chemistry and characterisation techniques, in particular X-ray and neutron powder and single-crystal diffraction as well as electron microscopy using in-house equipment as well as instrumentation at major national and international research facilities. In Chemistry Education projects were geared towards an understanding of how we best support student learning, e.g. by using Information & Communications Technology. Modulated Structures of Oxopyroborates A family of non-centrosymmetric oxo pyroborates, AMOB2O5 (A = K, Rb, Cs, Tl; M = Nb, Ta), have recently attracted considerable interest owing to their potential use as nonlinear optical materials. Previously the structure of KNbOB2O5, that adapts an eight-fold superstructure, was successfully solved and refined using a mixed conventional and superspace approach. Using average structure positions and refined atomic modulation functions it was possible to calculate and refine accurate atomic positional parameters in a superstructure model. This approach avoids problems in the refinement caused by often large numbers of either weak or unobserved satellite reflections and might be used more generally. For both KNbOB2O5 and the previously refined structure of RbNbOB2O5 (Schmid et al., 2000) apparent valence calculations show, that potassium and rubidium, respectively, are satisfactorily bonded, providing a key to understanding the cause of the modulation. Caesium, the largest A ion in this family, forms an unmodulated structure. The undistorted channels formed by the framework, however, are too large to provide the smaller ions with an adequate bonding environment. Instead the modulation reduces the size of the channels to fit those smaller ions. Temperature dependent X-ray powder diffraction patterns for some members of the family were collected at the Photon Factory, Tsukuba, Japan, with a view to better understand the driving forces that cause commensurate or incommensurate modulation. The Personalisation Hypothesis in Pre-Laboratory E-Learning Environments (Yeung, George, King†) There has been much research activity investigating best practices for design of multimedia instructional materials and for establishing effective e-learning environments. One area of such study has concerned the personalisation hypothesis, first proposed by in 2000. The hypothesis is that student learning in virtual environments is better facilitated by the use of personalised text forms (first person, more conversational style) than by non-personalised text forms (third person, more formal style). Findings supporting the hypothesis have been based on students’ performance on both retention and transfer tests, with most of the testing having been carried out in e-learning environments in the domains of physics and biology. This work set out to test the personalisation hypothesis using first year university students studying chemistry. The e-learning environments chosen involved compulsory pre-laboratory activities, used to prepare students to carry out experiments in acid-base chemistry. Approximately 600 students took part in the project, covering a range of levels of prior knowledge within the domain. Retention and transfer tests were carried out immediately after students’ had completed the pre-laboratory work and academic performance in this topic in the end-of-semester examination was Annual Research Report 85 also investigated. The importance of factors such as gender, language background, and learning style preferences were considered. Li-Intercalation and Solid State Batteries (Barisic) Compounds that can reversibly intercalate lithium have the potential to be used as cathodes in rechargeable lithium ion batteries. Two characteristics, the availability of interstitial or defect sites for the incorporation of lithium and the presence of reducible cations are found in some defect perovskites. The aim of this study is to synthesise a number of defect perovskites, which might be useful as host materials for Li intercalation, and investigate their structures using X-ray and neutron powder diffraction. Phases in the SrO-ZrO2-Nb2O5 system were investigated. Samples across the Sr0.7-xZr0.4-2xNb0.6-2xO3, 0.02 ≤ x ≤ 0.30, composition range have been prepared from starting oxides (Zr, Nb) and carbonates (Sr) in stoichiometric quantities. Samples were heated at 1400°C in air and repeatedly reground. It was found that the solid solution field extends from ~0.02 < x ≤ 0.3. Figure 1 shows the relationship between the cell dimensions and the composition (Sr content) of the sample. X-ray diffraction patterns have shown that all compositions adopt a cubic perovskite sub-structure but that the correct symmetry is lower in all cases. The resulting tetragonal Figure 1. Composition dependence of the lattice and orthorhombic space groups are indicated in Figure 1 parameters of Sr0.7+xZr0.4+2xNb0.6-2xO3, with a normalised as well. c value, c/√2. For the two-phase sample the I4/mcm c Neutron powder diffraction data were collected value is the larger of the two c values and the a value from four samples prepared in 15 g batches. After careful is the smaller of the two a values. characterisation of the structures for the Li free samples, these exact samples were then chemically intercalated with Li (via the butyl-lithium route). Lithium intercalation was carried out chemically on three samples of the Sr0.7+xZr0.4+2xNb0.6-2xO3 series with compositions x = 0.05, 0.10, and 0.15. Subsequently neutron diffraction patterns were collected for two of these samples at RT. It was found that only subtle changes were detectable in the neutron diffraction patterns. All the same reflections were present, at the same relative intensities. However, on closer inspection, it was evident that there were some distinct and fundamental differences between the two patterns, e.g. a reversal of intensity in some split peaks. The reversal results from a change in symmetry to a space group which has the a and c lattice parameters switched, i.e. Imma. The best fit was obtained using a two-phase Imma and I4/mcm model, with Imma being the predominant phase. The lowering in symmetry is possibly due to the fact that the lithium ions are extremely small and the oxygen octahedra need to tilt more in order to satisfy their bonding requirements. Given that intercalation of lithium results in the reduction of Nb5+ to Nb4+, the increased size of Nb4+ could be another reason behind the phase change. † Collaborators from outside the School of Chemistry Selected Publications 1. Norén, L, Withers, RL, Schmid, S, Brink, FJ and Ting, V. Old friends in a new light. “SnSb” revisited. J. Solid State Chem. 179, 404–412 (2006). 2. Schmid, S, Elcombe, M and Rhode, M. Defect perovskites in the SrO-ZrO2-Nb2O5 system. Australian Institute of Physics, Conference Proceedings ‘Wagga Wagga 2006’. On-line at http://www.aip.org.au/wagga2006/TP15_Schmid.pdf. 3. Yeung, A, George, A, Schmid, S and King, M. Testing the personalization hypothesis in pre-laboratory e-learning environments. Proceeding of the Assessment in Science Teaching and Learning Symposium. Sydney, NSW: UniServe Science, 146-152, 2006. 4. Schmid, S and T. The structure of KNbOB2O 5 – a commensurately modulated structure. Acta Crystallogr., B61, 361–366, 2005. Wagner, 5. Schmid, S and Yeung, A. The influence of a pre-laboratory work module on student performance in the first year chemistry laboratory. Research and Development in Higher Education, 28, 471– 479, 2005. 6. Yeung, A, Read, J and Schmid, S. Students’ learning styles and academic performance in first year chemistry. In Merrett, D (Ed.). Proceedings of Blended Learning in Science Teaching and Learning Symposium. Sydney, NSW: UniServe Science, 137–142, 2005. 7. Schmid, S. Early transition metal compounds with modulated structures. Habilitationsschrift (Habilitation Thesis), University of Tübingen, 2002. 8. Withers, RL, Schmid, S and Thompson, JG. Compositionally and/or displacively flexible systems and their underlying crystal chemistry. Prog. Solid State Chem., 26, 1–96, 1998. 86 School of Chemistry Dr Timothy Schmidt Room 457 School of Chemistry, F11 Telephone: +61 2 9351 2781 Facsimile: +61 2 9351 3329 Email: [email protected] http://www.chem.usyd.edu.au/about/staff_schmidtt.html Annual Research Report 87 Polycyclic Aromatic Hydrocarbons A possible class of molecules responsible for the DIBs are the large polycyclic aromatic hydrocarbon (PAH) molecules or their radicals. By obtaining gas phase excitation spectra of large PAH radicals and neutrals we are able to compare the absorption positions to the DIBs. Our current focus is a special class of PAH molecule called the all-benzenoid PAHs, a series of PAHs in which the structures may be drawn such that the electrons reside in benzenoid rings joined by “single bonds”. Indeed, these “single” bonds are longer by approximately 0.05Å compared to the intra-benzenoid bonds. We obtained the R2C2PI-TOF, laser-induced fluorescence and dispersed fluorescence spectra of triphenylene in 2006. The spectrum was analyzed in terms of Herzberg-Teller coupling, a breakdown of the crude Born-Oppenheimer approximation. The Red Rectangle (Rob Sharp, AAO) MOLECULAR SPECTROSCOPY AND QUANTUM THEORY The inner workings of molecules may be elucidated by performing sophisticated laser spectroscopic experiments, probing their electronic structure and nuclear dynamics. Experiments performed in the purest environment available, high vacuum, allow us to interrogate exotic molecules with a view to answering questions about molecules in similar environments, such as outer space, or very different environments, such as the condensed phase. Molecules in the interstellar medium and The group logo above shows a 2-D joint laser induced those invoked as molecular electronic devices share fluorescence / dispersed fluorescence spectrum of the in common the motif of conjugation. By exploiting Swan bands of C2 that looks uncannily like a comet trail, this link we are able to apply our fundamental in which C2 has been also observed. astrophysical research to applied problems in molecular electronics. The interpretation of our experimental data is guided by a set of computational tools. By testing our available quantum mechanical computational techniques against rigorous spectroscopic data, we can then apply these techniques with a degree of confidence to problems beyond the scope of direct measurement. Astrophysics and Molecular Spectroscopy The oldest unsolved problem in molecular spectroscopy is that of the identity of the carriers of the Diffuse Interstellar Bands (DIBs), a series of 300 diffuse absorption features exhibited in the spectra obtained of stars occluded by diffuse interstellar clouds. The carriers of the DIBs are widely believed to be conjugated carbon molecules with strong optical transitions. In 2006 we made the startling discovery of a molecular radical absorbing coincident with the diffuse interstellar band at 476 nm. The radical is the brightest fluorescent radical in a benzene discharge after C2 and C3. While this radical is likely to be aromatic, its exact chemical nature has so far eluded us and awaits investigation by resonant 2-colour 2-photon ionization time-of-flight mass-spectroscopy (R2C2PI-TOF). In late 2004, using the 8m Very Large Telescope of the European Southern Observatory, we obtained the highest-yet resolution spectra of the Red Rectangle, a nearby biconical proto-planetary nebula. The Red Rectangle exhibits a number of unidentified emission features which are presumably molecular. Modelling of the spectra suggests a large PAH carrier exhibiting sequence structure. We believe that discovery of the identity of the carrier of the Red Rectangle Bands will provide a “foot in the door” to the discovery of the DIB carriers. In the course of analyzing these spectra we identified the C2 molecule fluorescing in the walls of the nebula’s bicones. We have been able to model the behaviour of C2 and in doing so construct constraints on the carrier of the unidentified emission bands. In late 2006, Damian Kokkin and Rob Sharp obtained more C2 Swan spectra from the Red Rectangle which is currently under analysis. A New Band System of C2 (Kable, Nauta) Inspired by the observation of C2 in the Red Rectangle, and wishing to fully understand this phenomenon, we undertook an all-out assault on the C2 molecule using sophisticated quantum theory. Our results agreed to about 0.1% with experiment and have resulted in an upwards 21% revision of the abundance of C2 in the interstellar medium. One electronic state was seemingly ill-calculated. Closer inspection revealed that it has never been directly observed. We undertook to observe the d-c transition of C2 for the first time, finally revealing the true character of the c state. The original calculations were vindicated. Femtosecond Spectroscopy In collaboration with others, principally Ned Ekins-Daukes from the School of Physics, we obtained funding in 2005 for a femtosecond laser system. This is being installed in new laboratories 2007 and will open up a world of time-resolved and high-intensity laser experiments. Selected Publications 1. Kokkin, DL, Troy, TP, Nauta, K, Schmidt, TW. Gas phase spectra of all-benzenoid polycyclic aromatic hydrocarbons:  Triphenylene. J. Chem.Phys., 126, 019708, 2007. 2. Kokkin, DL, Bacskay, GB and Schmidt, TW. Oscillator strengths and radiative lifetimes forC2:  Swan, Ballik-Ramsay, Phillips and d3Pg← c3Su+ systems. J. Chem.Phys., 126, 304707, 2007. 3. Kokkin, DL, Reilly, NJ, Morris, CW, Nakajima, M, Nauta, K, Kable, SH and Schmidt, TW. Observation of the d3Pg ← c3S+u band system of C2. Journal of Chemical Physics, 125, 231101, 2006. 4. Reilly, NJ, Schmidt, TW and Kable, SH. Two-dimensional fluorescence (excitation/emission) spectroscopy as a probe of complex chemical environments. Journal of Physical Chemistry A, 110, 12355-12359, 2006. 5. Troy, TP and Schmidt, TW. A theoretical treatment of the absorption spectra of all-benzenoid hydrocarbons. Monthly Notices of the Royal Astronomical Society, 371, L41-L44, 2006. 6. Reilly, NJ, Cupitt, GC, Kable, SH and Schmidt, TW. An experimental and theoretical investigation of the dispersed fluorescence spectroscopy of HC4S. Journal of Chemical Physics, 124, 194310, 2006. 7. Kokkin, DL and Schmidt, TW. On the electronic properties of dehydrogenated polycyclic aromatic hydrocarbons. Journal of Physical Chemistry A, 110, 6173-6177, 2006. 8. Sharp, RG, Reilly, NJ, Kable, SH and Schmidt, TW. Sequence structure emission in the red rectangle bands. Astrophysical Journal, 639, 194-203, 2006. 88 School of Chemistry Emeritus Professor Sever Sternhell, FAA Honorary Staff Room 146 School of Chemistry, F11 Telephone: +61 2 9351 4421 Facsimile: +61 2 9351 3329 Email: [email protected] http://www.chem.usyd.edu.au/about/staff_sternhell.html areas of interest: Mechanochemistry Mechanical processes, e.g., ballmilling, can provide the energy needed for chemical reactions to proceed. Initial results indicate that rather unexpected reactions (e.g., transfer of hydrogen atoms) occur under such conditions and the primary aim of this project is to investigate them in a systematic manner. Practical possibilities include the destruction of persistent environmental pollutants, such as DDT. Induction of Chirality in Mesophases Mesophases, i.e., forms of matter intermediate between crystalline solids and liquids, may be made chiral by addition of small amounts of chiral inducers or dopants. Initial results gave a number of desirable structural characteristics for efficient dopands and include the most powerful dopands yet reported. Practical possibilities include better materials for liquid-crystal based display panels. Selected Publications 1. Cheung, J, Field, LD, Regaglia, FM and Sternhell, S. Synthesis of helical molecules based on 5,6,6a,7,8,12b-hexahydrobenzo[c]phenanthrene-5,8-diones. Aust. J. Chem., 48, 1707-1725, 1995. 2. Cheung, J, Field, LD, Hambley,TW and Sternhell, S. Inversion of helical molecules based on 5,6,6a,7,8,12b-hexahydrobenzo[c]phenanthrene-5,8-diones. Aust. J. Chem., 48, 1727-1740, 1995. 3. Field, LD, Sternhell, S and Kalman, JR. Organic Structures from Spectra. Second Edition, John Wiley & Sons, 1995. 4. Field, LD, Sternhell, S and Wilton, HV. Mechanochemistry of some hydrocarbons. Tetrahedron, 53, 4051-4062, 1997. 5. Cheung, J, Field, LD, Hambley, TW and Sternhell, S. Synthesis of chiral molecular template based on trans-5,6,6a,12b-hexahydro1,12-dimethylbenzo[c]phenanthrene-5,8-dione. J. Org. Chem., 62, 62-66, 1997. 6. Cheung, J, Field, LD and Sternhell, S. Highly efficient chirality inductors based on (5RS,8RS)-trans-5,6,6a,7,8,12b-hexagtdriveb zo[c]phenanthrene-5,8-diol. J. Org. Chem., 62, 7044-7046, 1997. 7. Field, LD, Sternhell, S and Wilton, HV. Mechanohydrogenation. Tetrahedron letters, 39, 115-116, 1998. 8. Park, JJ, Sternhell, S and Vonwiller, SC. Highly efficient chirality inducers based on steroid-derived 2,6,9-trioxabicylco[3.3.1]n onanes. J. Org. Chem., 63, 6749-6751, 1998. 9. Kalman, JR, Morgan, J, Pinhey, JT and Sternhell, S. Electrophilic metal-alkyl bond cleavage in tetraorganosilicon and tetraorganotin compounds by lead tetracarboxylates and aryllead tricarboxylates. Tetrahedron, 55, 3615-3624, 1999. 10. Field, LD, Sternhell, S andKalman, JR. Organic structures from spectra. Third Edition, John Wiley & Sons, 2002. Annual Research Report 89 90 School of Chemistry Annual Research Report Emeritus Professor Walter C Taylor, OAM Selected Publications Honorary Staff Room 146 School of Chemistry, F11 Telephone: +61 2 9351 2748 Facsimile: +61 2 9351 3329 Email: [email protected] http://www.chem.usyd.edu.au/about/staff_taylor.html areas of interest: Research centres on chemical and biological aspects of natural products. The aims are: (i) to study the constituents of plants in relation to their taxonomy (chemotaxonomy) and identify intermediates including novel products in biogenetic pathways; (ii) to isolate and study useful substances including pharmacologically active compounds. (a) The plant Schefflera leucantha (Araliaceae) is used widely in Thailand and China as an antiasthmatic. The active bronchodilator principle is a mixture of saponins; the pure  components have been isolated in order to establish the structures and to study the  biological properties. (b) The seeds of the Indonesian plant, Chydenathus sp. contain significant quantities of  saponins which are toxic to fish. The pure saponins are being isolated and their  structures elucidated by NMR and MS studies. (c) Members of the Guttiferae family [e.g. Garcinia mangostana (mangosteen)] are rich in xanthone derivatives, some of which have been found to be active as antibacterial/antifungal agents. Other members of the Guttiferae occurring in southern Thailand are being examined with a view to developing useful compounds. (d) Antiviral constituents of Clinacanthus nutans and anti-hypotensive constituents of Tacca chantrieri are being studied. Extensive collaborations exist with universities in Indonesia, Myanmar, Nepal, Thailand and Vietnam with botanists, chemists and biologists studying local floras used in traditional medicine. Eight papers were published in 2006. Current Projects: • • • • • • Bronchodilator constituents of Schefflera leucantha, and anti-hypertensive constituents of Tacca chantrieri. Antiviral constituents of Clinacanthus nutans Constituents of Garcinia spp.; antibacterial derivatives of mangostin Constituents of Thai medicinal plants Constituents of medicinal plants of Myanmar Constituents of endophytic fungi 91 1.   Nguyen, MC, Taylor, WC and Sung, TV. A new cyclobutane lignan from Cinnamomum balansae.  Natural Product Letters, 15, 331338 2001. 2.  Tuntiwach-wuttikul, P and Taylor, WC. New rearranged clerodane diterpenes from Tinospora baenzigeri. Chem. Pharm. Bull., 49, 854-857 2001. 3.  Tuchinda, P, Reutrakul, V, Claeson, P, Pongrayoon, U, Sematong, T, Santisuk, T and Taylor, WC. Anti-inflammatory cyclohexenyl chalcone derivatives in Boesenbergia pandurata. Phytochemistry, 59, 169-173, 2002. 4. Rukachaisirikul, V, Sukpondma, Y, Jansakul, C and Taylor, WC. Isoflavone glycosides from Derris scandens. Phytochemistry, 60, 827-834, 2002. 5. Nguyen, MC, Tran, VS and Taylor, WC. Biological activity of glypetoline, a sulfur-containing indole alkaloid from Glycosmis petelotii. J. Materia Medica Hanoi, 7, 24-27, 2002. 6. Rukachaisirikul, V, Ritthiwigrom, T, Pinsa, A, Sawangchote, P and Taylor, WC. Xanthones from the stem bark of Garcinia nigrolineata. Phytochemistry, 64, 1149-1156, 2003. 7. Tuntiwach-wuttikul, P, Rayanil, K and Taylor, WC. Chemical constituents from the flowers of Nyctanthes arbor-tristis. ScienceAsia, 29, 21-30, 2003. 8. Rukachaisirikul, V, Painuphong, P, Sukpondma, Y, Koysomboon, S, Sawangchote, P and Taylor, WC. Caged-triprenylated and -tetraprenylated xanthones from the latex of Garcinia scortechinii. Journal of Natural Products, 66, 933-938, 2003. 9. Rukachaisirikul, V, Kamkaew, M, Sukavisit, D, Phongpaichit, S, Sawangchote, P and Taylor, WC. Antibacterial xanthones from the leaves of Garcinia nigrolineata. Journal of Natural Products, 66, 1531-1535, 2003. 10. Tuntiwachwuttikul, P, Pootaeng-on, Y, Pansa, P, Srisanpang, T and Taylor, WC. Sulfur-containing compounds from Clinacathus siamensis. Chemical and Pharmaceutical Bulletin Japan, 51, 1423-1425, 2003. 11. Rukachaisirikul, V, Pailee, P, Hiranrat, A, Tuchinda, P, Yoosook, C, Kasit, J, Taylor, WC and Reutrakul, V. Anti-HIV-1 protostane triterpenes and digeranylbenzophenone from trunk bark and stems of Garcinia speciosa. Planta Medica, 69, 1141-1146, 2003. 12. Deachathai S, Mahabusarakam W, Phongpaichit S and Taylor WC. Phenolic compounds from the fruit of Garcinia dulcis. Phytochemistry, 66, 2368-75. 2005, 13. Mahabusarakam W, Chairerk P and Taylor WC. Xanthones from Garcinia cowa Roxb. latex. Phytochemistry, 66, 1148-53, 2005. 14. Rukachaisirikul, V, Phainuphong, P, Sukpondma, Y, Phongpaichit, S and Taylor, WC. Antibacterial caged-tetraprenylated xanthones from the stem bark of Garcinia scortechinii. Planta Medica, 71,165-70, 2005. 15. Son, PT, Giang, PM and Taylor, WC. NMR studies of darutoside, a rare ENT-pimarane glucoside. Natural Product Research, 19, 503-7, 2005. 16. Deachathai, S, Mahabusarakam, W, Phongpaichit, S, Taylor, WC, Zhang, Y-J and Yang, C-R. Phenolic compounds from the flowers of Garcinia dulcis. Phytochemistry, 67, 464-469, 2006. 17. Mahabusarakam, Nuangnaowarat, W and Taylor, WC. Xanthone derivatives from Cratoxylum cochinchinense roots. Phytochemistry, 67, 470-474, 2006. 18. Pittaya, T, Photchana, P, Yupa, P and Taylor, WC. Chromones from the branches of Harrisonda perforata. Chemical & Pharmaceutical Bulletin, 54, 44-47, 2006. 19. Pittaya, T, Photchana, P, Yupa, P and Taylor, WC. Chemical constituents of the roots of Piper Sarmentosum. Chemical & Pharmaceutical Bulletin, 54, 149-151, 2006. 20. Taechowisan, T, Wanbanjob, A, Tuntiwachwuttikul, P and Taylor, WC. Identification of Streptomyces sp Tc022, an endophyte in Alpinia galanga, and the isolation of actinomycin D. Annals of Microbiology, 56, 113-117, 2006. 21. Mahabusarakam, W, Kuaha, K, Wilairat, P and Taylor, WC. Prenylated xanthones as potential antiplasmodial substances. Planta Medica, 72, 912-916, 2006. 22. Panthong, K, Pongcharoen, W, Phongpaichit, S and Taylor, WC. Tetraoxygenated xanthones from the fruits of Garcinia cowa. Phytochemistry, 67, 999-1004, 2006. 23. Willis, AC, O’Connor, PD, Taylor, WC and Mander, LN. The absolute stereochemistry of the Galbulimima alkaloids. Australian Journal of Chemistry, 59, 629-632, 2006. 92 School of Chemistry Dr Pall Thordarson Room 509a School of Chemistry, F11 Telephone: +61 2 9351 4456 Facsimile: +61 2 9351 3329 Email: [email protected] http://www.chem.usyd.edu.au/about/staff_pall.html biomimetic chemistry and nanotechnology The most complex and elegant examples of “nanotechnology” come from Nature. In our group we first look to Nature for inspiration when it comes to solving the problems we are currently dealing with in nanotechnology (e.g., biosensors or tissue engineering). Methods to direct the assembly of functional molecules are of particular interest to us as are methods to analyse nanostructures, e.g. by the use of scanning probe microscopy (AFM and STM). Light-Activated Bioconjugates (Peterson, Prasad, Smith*) We are developing novel ways to control the function of redox proteins using light as the external input signal. The focus will be on using synthetic chromophores, conjugated either to proteins (direct activation) or to biological co-factors such as NAD—nicotinamide adenine dinucleotides— (indirect activation). In the first project we have synthesized a series of bioconjugates between synthetic donor chromophores (Ru-terpyridines) and a redox acceptor protein (cytochrome c). Using laser spectroscopy, we have been able to demonstrate that photoinduced electron transfer (see figure – below) takes place between the donor and protein-acceptor upon excitation of the Ru-terpyridine. In the second project, we have shown that our photocatalyst is capable of reducing NAD and we are now currently optimising its performance by synthesizing NAD modified with our photocatalyst. We will continue to develop the application of these conjugates in three areas: biosensing, synthesis, and single-molecule research. Annual Research Report 93 bio-mimetic ECM materials for applications in tissue engineering and drug delivery. We recently discovered a novel family of LMOG 1 (see figure – below) that form gels in hexanes and other non-polar solvents that collapse upon addition of small anions such as Cl- and Br-. We are now investigating how we can utilize the unique properties of our LMOG 1 to create a new type of “smart”gels for biomedical applications (e.g., cancer therapy). Nanostructural Microscopy (Chin, Crossley, Hush, Larsen, Reimers, Braet*, Elemans*) To analyse chemical structures on the nanoscale (1-100 nm), we can no longer rely on traditional techniques such as NMR spectroscopy. We need to resort to the use of high-resolution microscopy, and we have several on-going projects in this area. The largest of these is on the creation of a molecular memory in collaboration with Intel Inc. that the Molecular Electronics Group (Crossley, Hush, Reimers and Thordarson) is currently undertaking. This project received an ARC Linkage grant in 2004 and work is now on-going to develop the microscopy techniques (AFM and STM) that are necessary to characterise the molecular memory components. Other projects our group is working on within this area are: Single molecule imaging (see figure – below) of catalytic porphyrins (Crossley, Elemans) and electron microscopy (TEM and SEM) studies of self-assembled gels from small molecules (Braet). Selected Publications Self-Assembled Gels (Tong, Webb, Braet*) The extra-cellular matrix (ECM) outside the cell in multi-cellular organisms is a gel-like material, consisting mostly of proteins such as elastin and collagen. Bio-mimetic materials that resemble the ECM are of particular interest as they can be designed to interact favourably with the surrounding tissue, e.g., by stimulating a particular type of cell growth. Self-assembed gels formed from low molecular-mass organic gelators (LMOG) seem to be superior to polymeric gels as 1. Thordarson, P, Bijsterveld, EJA, Rowan, AE and Nolte, RJM. Epoxidation of polybutadiene by a topologically linked catalyst. Nature, 424, 915-8, 2003. 2. Scanning Tunneling Microscopy and Spectroscopy Studies of Porphyrins at Solid-Liquid Interfaces. B Hulsken, R van Hameren, P Thordarson, J W Gerritsen, R J M Nolte, A E Rowan, M J Crossley, J A A W Elemans and S Speller, Jpn. J. Appl. Phys., 45, 1953-5, 2006. 3. Developments in using Scanning Probe Microscopy to study Molecules on Surfaces – From Thin Films and Single-molecule Conductivity to Drug-living Cell Interactions. P Thordarson, R Atkin, W H J Kalle, G G Warr and F Braet, Aust. J. Chem., 59, 359-75, 2006. 4. Well-defined Protein-Polymer Conjugates – Synthesis and Potential Applications. P Thordarson, B Le Droumaguet and K Velonia, Appl. Microbiol. Biotechnol., 73, 243-54, 2006. 5. Real-Time Single Molecule Imaging of Alkene Oxidation by Manganese Porphyrins at a Liquid-Solid Interface. B Hulsken, R van Hameren, J W Gerritsen, T Khoury, P Thordarson, M J Crossley, A E Rowan, R J M Nolte, J A A W Elemans and S Speller, Nature Nanotechnology, 2, 285-9, 2007. 94 School of Chemistry Dr Matthew Todd Room 545 School of Chemistry, F11 Telephone: +61 2 9351 2180 Facsimile: +61 2 9351 3329 Email: [email protected] http://www.chem.usyd.edu.au/about/staff_todd.html Chemical Biology of Schistosomiasis Schistosomiasis (Bilharzia) is one of the most burdensome of the neglected tropical diseases, affecting more than 400 million people worldwide.4 The drug used to treat this disease, Praziquantel (rac-3), is currently being administered in mass chemotherapy programs in Africa. This will inevitably lead to the development of resistance, and no back-up drugs exist for the treatment of schistosomiasis. With an international group of collaborators, we seek new drugs for this disease through the synthesis of analogues and through discovering the as-yet unknown in vivo target of PZQ.5 Pictured right: The Biomphalaria snail, the intermediate host of the parasite principally responsible for Bilharzia in Africa, Schistosoma mansoni. Biosensing and Molecular Recognition Synthesis and chemical biology Two projects are currently underway in collaboration with Lisa Hall at Cambridge and Mike Watkinson at Queen Mary, London. We are building macromolecular constructs for biosensing applications. These consist of metal complexes of aza-macrocycles attached to a molecular recognition scaffold which in our model studies is either biotin or a mimic of a tripeptide sequence (RGD) known to be important in cell adhesion. The molecular recognition events are designed to be detected either electrochemically (with scoprionlike complexes shown here) or with surface plasmon resonance, and are easily variable, making them useful for a the early detection and diagnosis of various disease states. We have an interest in synthesising small organic molecules in interesting ways, as well as using them to probe various biological processes. Nonlinear Effects in Asymmetric Catalysis It is reasonable to expect a linear relationship between the enantiomeric excess (e.e.) of a catalyst employed in a chemical reaction and the e.e. of the product of that reaction. There are many cases known where this is not the case.1 Sometimes a very high excess of one enantiomer can arise from a nearly racemic catalyst. Such ‘Nonlinear Effects’ (NLEs) may have wide use in industrial synthesis, as well as playing some role in the origin of asymmetry in life. We are aiming to understand such effects in several model systems with a combination of experimental and computational approaches in asymmetric catalysis, so that we might develop a predictive model of when NLEs occur. Pictured left: Minimised Structures for Noyori’s DAIB Ligands Displaying High Asymmetric Amplification by a Positive NLE. 95 Annual Research Report Open Source Research Methods We have recently become involved with a group of biologists, lawyers and computer scientists known as The Synaptic Leap.6 We are interested in whether open source methods, which have produced such enormous successes in computer science (Linux, Firefox, Wikipedia etc) can be extended more generally to biomedical research.7 Current projects focus on the tropical diseases schistosomiasis and malaria. Asymmetric Organocatalysis Several small organic molecules have in recent years been shown to be very effective at catalysing constructive organic reactions in aqueous, metal-free systems. For example the amino acid proline can catalyse the aldol reaction with remarkable efficiency and stereoselectivity. We are seeking to understand such reactions and have begun with a study of asymmetric catalysis in the aza-Henry reaction (1 to 2), for the synthesis of the active enantiomer of the important anti-parasitic drug Praziquantel (3).2 Heterocyclic Methodology The enediamides (e.g. 4) are a novel class of heterocyclic compounds we have discovered and investigated.3 They display interesting reactive characteristics we are exploiting for the construction of small molecule mimics of peptide secondary structure such as β-turns (6). We have shown that the chemistry of the double bond contained in these heterocycles is highly stereoselective, directed by the stereocentre from the amino acid used in the ring synthesis. Selected Publications 1. Todd, MH. Asymmetric autocatalysis: Product recruitment for the increase in the chiral environment (PRICE). Chem. Soc. Rev., 31, 211-222, 2002. 2. El-Fayoummy, S, Mansour, W and Todd, MH. Solid phase synthesis of praziquantel. Tetrahedron Lett., 47, 1287-1290, 2006. 3. Todd, MH, Ndubaku, CO and Bartlett, PA. Amino acid-derived heterocycles: Lewis acid-catalyzed and radical cyclizations from peptide acetals. J. Org. Chem., 67, 3985-3988, 2002. 4. Fenwick, A, Savioli, L, Engels, D, Bergquist, R and Todd, MH. Drugs for the control of parasitic diseases: Current status and development. Schistosomiasis. Trends in Parasitology, 19, 509-515, 2003. 5. Kusel, JR, Oliveira, FA, Todd, M, Ronketti, F, Lima, SF, Mattos, ACA, Reis, KT, Coelho, PMZ, Thornhill, JA and Ribeiro, F. The effects of drugs, ions, and poly-l-lysine on the exretory system of Schistosoma mansoni. Instituto Oswaldo Cruz, Rio de Janeiro, 101, 293-298, 2006. 6. http://www.thesynapticleap.org/ 7. a) Kepler, TB, Marti-Renom, MA, Maurer, SM, Rai, AK, Taylor, G and Todd, MH. Open source research – the power of us. Aust. J. Chem., 59, 291-294, 2006; b) Todd, MH. Open access and open source in chemistry. Chemistry Central Journal, 1:3, 2007. 8. Tamanini, E, Watkinson, M and Todd, MH. Improved synthesis of the valuable peptidomimetic intermediate 3-azido-4-hydroxy cyclopentanoic acid. Tetrahedron: Asymmetry, 17, 2235-2239, 2006. 9. Ismail, MAH, Barker, S, Abou El Ella, DA, Abouzid, KAM, Toubar, RA and Todd, MH. Design and synthesis of new tetrazolyl- and carboxy-biphenylylmethyl-quinazolin-4-one derivatives as angiotensin II AT1 receptor antagonists. J. Med. Chem., 49, 1526-1535, 2006. 96 School of Chemistry Professor Gregory G Warr Room 310 School of Chemistry, F11 Telephone: +61 2 9351 2106 Facsimile: +61 2 9351 3329 Email: [email protected] http://www.chem.usyd.edu.au/about/staff_warr.html Annual Research Report Self-Assembly of Block Co-oligomers (Blom, Hawkett, Ganeva) We have prepared a range of novel amphiphilic block co-oligomers using controlled radical polymerization (RAFT) in which the hydrophobic and hydrophilic block structure and composition are systematically varied. These amphiphiles lie in a little-understood composition range between surfactants and block copolymers, where the relaxation time for self-assembly is one of the key parameters. Using a combination of small-angle x-ray and neutron scattering and optical microscopy, we have investigated the structure and stability of micelles, vesicles and liquid crystal phases they form in aqueous solution under various solution conditions, and how the relaxation dynamics can be used to tune the equilibrium structure, and also manipulate the system between equilibrium and kinetically-trapped states. The living nature of RAFT polymerization gives us the added capability to further grow the polymer chains in situ, leading to new polymeric nanostructures. Emulsion Structure and Stability (Beattie, Djerdjev, Jain, Hawkett, Whitby) soft matter and surfaces Our research is aimed at understanding the behaviour of amphiphilic compounds in bulk phases (solutions, liquid crystals, complex fluids), in colloidal systems (emulsions, foams, dispersions), and at interfaces. In a wide range of projects we examine the structure and dynamics of bulk phases and dispersions using techniques including neutron and x-ray scattering, optical microscopy, rheology and calorimetry, and interfacial structure by neutron reflectometry, adsorption isotherms, atomic force microscopy, and surface force measurements. By combining these techniques we are discovering new structures formed when surface-active molecules adsorb at the solid/liquid interface or when complex fluids abut an interface, and use this to design new nanostructured materials. Polymerisable Surfactant Nanostructures (Topp, Chatjaroenporn, Kurihara,* Schwering*) Polymerisable surfactants – surfmers – have the potential to capture and render permanent the complex nanostructures formed by amphiphilic self-assembly. Our two projects in this area address bulk self-assembly structure and ultra-thin polymerisable films. We have discovered a new controlled polymerisation mechanism by which we can prepare surfactant oligomers or polymers with tunable properties, thereby kinetically trapping polymeric surfactant aggregates to preserve the spontaneous self-assembly structure of the surfmer (Topp). This mechanism, as well as conventional free-radical photopolymerisation is being used to polymerise adsorbed layers of surfmers into ultra-thin, laterally nanostructured films as permanent coatings on various solid substrates (Chatjaroenporn, Schwering, Kurihara). Structure and Self-Assembly in Ionic Liquids (Araos, Atkin, McAlpine, Hernandez*) We have prepared several new ammonium nitrate, formate and thiocyanate room-temperature ionic liquids, i.e. salts that melt below room temperature, and shown that surfactants can self-assemble into micelles and liquid crystals and can form microemulsions in these compounds as well as commercial ionic liquids, and can also form structured aggregates at ionic liquid/solid interfaces. The micellar structure is weakly sensitive to the chemical composition of the ionic liquid, but the phase behaviour strongly depends on the hydrogen-bonding network.(McAlpine, Hernandez) The structure and stability of microemulsions closely parallels water-based systems, with a structure that evolves from ol continuous through bicontinous to ionic liquid continuous with increasing temperature. Small-angle neutron scattering has revealed unusual ordering of the oil and ionic liquid domains within bicontinuous microemulsions. (Atkin) The alignment and orientation of the constituent ions of these unusual liquids at solid surfaces has been shown by atomic force microscopy. Electrostatic and dispersion interactions within the liquid compete with the solid substrate to determine cation binding and orientation. (Atkin) We use water-in-oil emulsions containing magnetic nanoparticles (aqueous ferrofluid emulsions) to investigate the colloidal forces that stabilise them by magnetic chaining. The magnetic nanoparticles align in an external field, leading to strings of evenly-spaced droplets. As the field strength is changed, so does the separation between droplet surfaces and the droplets may deform. The changing structure of the dispersion is revealed by small-angle neutron scattering (see scattering patterns at right). By changing emulsifier type and concentration, and the composition of the continuous phase, we gain new insights into the factors that enhance emulsion stability. This work has also led to advances in the design of stable, aqueous ferrofluids. (Jain, Hawkett) We have also used small-angle and ultra-small-angle neutron scattering to probe the structure of oil-in-water emulsions that are believed to be stabilized by a nanoparticle adsorbed layer in the droplet surface. (Whitby, Djerdjev, Beattie) Emulsion Structure and Stability (Blom, Atkin, Zana) Our ongoing investigations of the adsorbed layer structure of surfactants on solid surfaces in equilibrium with aqueous (or ionic liquid) solutions has continued, principally using neutron reflectometry and atomic force microscopy. The growth of well-defined adsorbed bilayers has been shown to occur by quite distinct mechanisms for different double-chained ionic surfactants. The gradual breakup of such adsorbed bilayers induced by uptake of a more soluble surfactant has been observed. Whereas on mica this occurs via a well-defined progression of aggregate curvature through a mesh into cylinders and globular adsorbed aggregates, this is far less clear on quartz. The essential role of surfactant packing and aggregate curvature on mica has also been demonstrated in mixtures of soluble surfactants. (Blom) The relationship between molecular structure of monomeric and gemini surfactants and their adsorbed layer morphologies has been investigated, and this will continue as we investigate oligomeric and polymerized adsorbed surfactant films. (Zana) Selected Publications 1. Vesiculated Polymer Particles. Australian Provisional Patent number 12844010, October 2006 2. Atkin, R and Warr, GG. Structure in confined room temperature ionic liquids. J. Phys. Chem. C, 111, 5162-68, 2007. 3. Whitby, CP, Djerdjev, AM, Beattie, JK and Warr, GG. In situ determination of the size and polydispersity of concentrated emulsions. Langmuir, 23, 1694-1700, 2007. 4. Blom, A, Warr, GG and Wanless, EJ. Growth of adsorbed layers of double-chained cationic surfactants on mica. Aust. J. Chem., 59, 381-385, 2006. 5. Blom, A and Warr, GG. Structure and composition of cationic-nonionic surfactant mixed adsorbed layers on mica. Langmuir, 22, 6787-6795, 2006. 6. Whitby, CP, Djerdjev, AM, Beattie, JK and Warr, GG. Nanoparticle adsorption and stabilization of surfactant-free emulsions. J. Colloid Interface Sci., 301, 342-345, 2006. 7. Duval, FP, Zana, R and Warr, GG. Adsorbed layer structure of cationic gemini and corresponding monomeric surfactants on mica. Langmuir, 22, 1143-1149, 2006. 97 98 School of Chemistry Research Centres 100 School of Chemistry Annual Research Report Key Personnel in the OSC are: Director: Dr Mal D McLeod (School of Chemistry) Director: Dr Malcolm McLeod The Organic Synthesis Centre within the School of Chemistry, Building F11 Room 517 Telephone: +61 2 9351 5877 Facsimile: +61 2 9351 6650 Email: [email protected] http://osc.chem.usyd.edu.au/ Deputy Director: Dr Kate A Jolliffe (School of Chemistry) Executive Officer: Dr Pat J Stamford (School of Chemistry) Mr Matthew Fitzhenry and Dr Paulo Da Silva S ynthetic Organic Chemistry has been a focal point and a real strength in the School of Chemistry for more than 50 years and the School has hosted some of Australia’s foremost synthetic chemists. Over this period, many members of the School have willingly provided chemical expertise and specialised organic synthesis, not only to the research community within the University, but also to external agencies requiring these services. This demand provided the platform for the formation of the Sydney Organic Synthesis Unit in 1999 which specialised in custom synthesis, contract research and consultancy. By 2003, growing demand for contract synthesis provided the impetus to formally adopt the Unit as a Centre within the University. In 2003, the University of Sydney and the School of Chemistry invested in new equipment for the Organic Synthesis Centre (OSC) and by August 2004 building works on dedicated OSC laboratories and offices were completed. The OSC now occupies a modern, state-of-the-art organic chemistry laboratory. Beside these recent investments, the OSC draws on the extensive expertise of the academic and research staff within the School of Chemistry and the exceptional range of research facilities available within the Centre, the School of Chemistry and the University of Sydney as a whole. The aims of the OSC are to provide focus and support for synthesis-related research programs in the University, provide an opportunity for contract synthesis to Government Organisations and to Industry, develop relationships with Industry and to establish funded research programs. In providing professional services to industry and the chemical research sector the OSC acts as one of the commercial enterprises of the School of Chemistry. Over the last 12 months, the OSC has been able to provide a wide and unique range of services to many agencies both public and private. These have included: (i) the synthesis of high quality specialist organic chemicals for the pharmaceutical, biotechnology and materials industries in quantities from milligrams to kilograms; (ii) the development and formulation of synthetic strategies for new compounds as well as assessment and optimisation of synthetic schemes; (iii) the active involvement in research programs through the design and provision of novel compounds for various applications; (iv) consultancy and the provision of expert witnesses; (v) the provision of expertise to support applications for research funding where there is a need for professional organic synthesis; and (vi) the provision of research assistance (on a contract or long-term basis) in research programs that require the on­going synthesis of organic compounds. The OSC also provides a service to the wider Australasian Organic Chemistry community through the development and hosting of OrgNet Australasia. OrgNet is a free email network regulated by the OSC for Australasian Organic Chemists to enable the rapid dissemination of important messages and information. In addition to the professional services offered by the OSC, members of the OSC staff are also involved in primary research activities. This research is either co­operative (i.e. where OSC participates in a program collaboratively with other research groups within the University) or more fundamental (e.g. developing new practical methods for molecular synthesis). Current programs of research include investigations into expanding the synthetic toolbox available to practicing chemists through the re-evaluation of many long-established synthetic methodologies together with related aspects of biomimetic and chemo-enzymic synthesis (Dr Pat Stamford). 101 102 School of Chemistry Annual Research Report 103 Research grants and publications by members of the CHMR are presented in the School publication and are not separately listed here. Acting Director: Professor Peter Lay The Centre for Heavy Metals Research within the School of Chemistry, Building F11 Room 307 Telephone: +61 2 9351 4269 Facsimile: +61 2 9351 3329 Email: [email protected] http://chmr.chem.usyd.edu.au/ T he Centre for Heavy Metals Research (CHMR) is based in the School of Chemistry with linkages to other units within the University, as well as to participating institutions both within and outside Australia. It has as its major goal the instigation and development of a substantial research program in the chemistry of heavy metals and to develop interactions with industry, hospitals and government institutions. The Centre is the first of its kind to be established in Australia. The CHMR builds on a long tradition of internationally recognised expertise within the University on the chemistry of the ‘heavy’ metals. Through its three research interests, designated respectively as Bio-Metals, IndustryMetals, and Environ-Metals, it places emphasis on the social and economic benefits of such research to areas of Health, Industry and the Environment. Individual projects range from the discovery of novel metal-based human and veterinary pharmaceuticals or the development of new industrial catalysts to methods for recovery and recycling metal-containing waste streams and to modelling the fate and transport of heavy metals in the natural environment. This represents an identifiable grouping of many of the established research activities of the Centre’s academic staff. A selection of current CHMR projects include the synthesis and characterisation of new porous materials that display reversible exchange of molecular guests for use in separation processes (Dr Cameron Kepert), negative-thermal expansion materials that are generating commercial interest (Dr. Cameron Kepert), hydrocarbon oxidation catalysts (Dr James Beattie, A/Prof. A. F. Masters and collaborators in the Netherlands), the distribution of metal ions in synthetic clays (Assoc. Prof. Brendan Kennedy), metal-based drugs, nutritional supplements and metal-induced cancers (Prof. Peter Lay), heme proteins (Assoc. Prof. Robert Armstrong and Prof. Peter Lay), Pt and Co anti-cancer drugs (Prof. Trevor Hambley, and studies of metallo-proteins expressed by extremophilic microorganisms and their potential applications in biotechnology (Dr Rachel Codd). The CHMR underwent a review in 2006 that was chaired by the Pro-Vice Chancellor (CST), Professor Beryl Hesketh. The Centre received a favourable review from the committee and it was recommended that it should continue as a Centre, but some discussions would be held within the School to appoint a new director and to determine whether changes in direction and name were desirable. These discussions have been ongoing during the latter half of the year. Commercialisation Professors Hambley and Lay were involved in the commercialisation of metal anti-inflammatory drugs both as veterinary and human pharmaceuticals with Nature Vet Pty Ltd and Medical Therapies Ltd through an ARC Linkage grant and a substantial research contract from Medical Therapies. Commercialisation of Professor Kepert’s negative thermal expansion research has continued through UCOM-10, a University start-up company that has been funded by venture capital. Key Personnel in CHMR are: Acting Director: Professor Peter A Lay, FAA School of Chemistry Associate Director (Bio-Metals): Professor Peter A Lay School of Chemistry Associate Director (Industry-Metals and Environ-Metals): Associate Professor James K Beattie School of Chemistry 104 School of Chemistry Annual Research Report 105 has plagued the characterization of polymers worldwide: that of band broadening in size-exclusion (gel-permeation) chromatography. We have among the world’s best equipment for the synthesis and characterization of polymer colloids, thanks to ARC LIEF grants and through generous support from the University of Sydney, as well as specialist equipment provided by industry. Director: Professor Gregory G Warr Key Centre for Polymer Colloids within the School of Chemistry, Building F11 Room 310 Telephone: +61 2 9351 2106 Facsimile: +61 2 9351 8651 Email: [email protected] http://www.kcpc.usyd.edu.au/ I n its eighth year, the KCPC con­tinues to be one of the most dynamic research centres in Australia, and is recog­nized internationally as a world leader in research into emulsion polymer­ization and related fields. We have made sub­ stantial contributions to in­ternational science in our publications, training, in­dustry collabora­tion, and out­reach. This would not have been possible without the high levels of profes­sionalism and expertise of our staff. The Centre’s researchers have come from every continent, and reflect our emphasis on cultural diversity. We continued to enjoy strong links with aca­demic, govern­ment, and industrial research­ers in Australia, and also in Ger­many, France, Thai­land, Malaysia, the US and South Africa. Our research covers a wide range of basic and applied aspects of polymer colloids in synthetic and natural systems. In emulsion polymer­ization, breakthroughs in 2006 have led to an understanding of radical entry and exit in (electro)sterically stabilized particles. In a project sponsored by the ARC and our industry partner Dulux, we have developed a model for particle formation in RAFT mediated ab initio emulsion polymer­ization systems that paves the way for the preparation of very small (< 20 nm) monodisperse latex particles without free surfactant. Also in this project, work has continued on i) our new approach to miniemulsion polymerization that avoids the use of labile surfactant and the use of a hydrophobic stabilizer; ii) using reversible addition fragmentation chain transfer (RAFT) controlled radical processes to achieve the individual coating of paint pigment particles with binder polymer, where we have made very significant breakthroughs that have resulted in two patents so far; iii) a study of self assembly processes in block copolymers that can lead to polymerizable hollow particles. In a project sponsored by the ARC and Dyno Nobel we are investigating the mechanisms for the generation and control of gas bubbles in explosive emulsions. In a project sponsored by the ARC and Sirtex Medical we are exploring the use of superparamagnetic nanoparticles in the hyperthermia treatment of liver cancer and other biomedical applications. Making use of the technology developed in the Dulux project we have perfected techniques to individually coat magnetic nanoparticles with polymer. In collaboration with the International Rice Re­search Institute (Manila), we have made advances in applying to starch key tech­niques that were developed in the field of syn­thetic polymer colloids for character­ization and understanding form­ation mecha­nisms. This has led to a powerful new method to probe the enzymatic processes in starch biosynthesis for rice and other grains. Each enzymatic step can now be as­sociated with par­ticular regions in the mo­lecular weight distribu­tions of the starch. We have also developed new methods for characterizing and interpreting the size distribution of starch and other polysaccharides. These methods have enormous potential in food science. We have developed methods for obtaining rate coefficients for starch biosynthesis from in-vitro synthesis, again from the evolution of mo­lecular weight distribution during polymer growth. This work has led to a widely applicable method for overcoming a prob­lem that Director: Professor Gregory G Warr School of Chemistry F11 Telephone: +61 2 9351 2060 Faximile: +61 2 9351 3329 Email:[email protected] Deputy Director and Development Manager: Dr Brian S Hawkett School of Chemistry F11 Telephone: +61 2 9351 6973 Faximile: +61 2 9351 8651 Email: [email protected] 106 School of Chemistry Research Facilities 108 School of Chemistry Summary of Facilities and Techniques T he School contains or is involved with joint facilities covering a diverse array of state-of-the-art instrumentation, worth well over $10M. In addition, we have extensive collaborations with major synchrotron radiation and neutron sources, allowing access to the some of most sophisticated and expensive instrumentation in the World, on a project specific basis. Further information on facilities and researchers in the School can be found on the Internet (http://www.chem.usyd.edu.au/). AAS Spectrophotometry - Varian Spectra AA-20 including graphite furnace; Varian Spectra AA-800; Varian AA220; Flame photometers for alkali metal analysis. Annual Research Report 109 Photon Correlation Spectrometer, Malvern HPPS system, Malvern ZetaSizer, Particle Size Distribution Analyser (PLPSDA),Dilatometers, Capillary Hydrodynamic Fractionator (CHDF), Ultracentrifuge, Ozonolyzer, Avestin EmulsiFlex, Autoclave, IKA Ultra Turrax T25 &T45, Schlenk Line, Dialysis and Ultrafilteration, Thermomixer, Ultrasonicators, Ovens, Optical Microscopes, Conductivity and pH Meters, Brookfield Viscometer, Karl Fischer Titer, Raman Probe, VMA-Getzmann Dispermat, KSV Sigma 70 surface Tensiometer, SensaDyne QC3000 Surface Tensiometer, a wide range of polymerization reactors (including computer controlled ones). Laser Techniques - Nd:YAG lasers (1064 nm, 532 nm, 355 nm, 266 nm, up to 100 Hz repetition rate); Excimer lasers (157 nm, 193 nm, 248 nm, 308 nm, up to 50 Hz rep rate), Dye lasers (tunable from ~215 - 800 nm, repetition rate determined by pump laser above); Optical Parametric Oscillator (20 Hz signal 440nm - 710 nm, idler 710 - 1800 nm); iCCD Spectrograph (3 gratings in turret); Scanning monochromators (1 x high resolution, several lower resolution instruments); Fluorescence detection; Time-of-Flight Mass-Spectrometry ion detection Magnetic Measurements Including access to a SQUID. Catalysis Laboratory - Range of small scale catalytic reactors with on line sampling GC. Mass Spectrometry - 4 instruments including: Polaris-Q (CI/EI)GC-MS with autosampler; Micromass TofSpec2E (MALDI-TOF); LCQ (Electrospray) and a LCQ Deca (Electrospray)with a HPLC system. There is also access to a QSTAR XL hybrid LC/MS/MS (in School of Molecular and Microbial Biosciences for high resolution measurements on proteins, DNA fragments, transition metal and organometallic species). CD Spectroscopy - Modern JASCO CD spectropolarimeters. Mixing and Grinding - Retsch MM 200 mixer mill and Retsch PM 100 high-energy planetary ball mill. Computational Chemistry and Molecular Modelling - High performance computing facilities include access to the Australian Centre for Advanced Computing and Communications (AC3) and the Australian Partnership for Advanced Computing (APAC), with a wide range of software packages available (e.g., Gaussian, Materials Studio, Spartan, Turbomole). New Equipment for 2005/2006 obtained through ARC LIEF grant (LE0560680) include:- Renishaw Raman inVia Microprobe with five excitation lines including: 488, 514, 633, 785, 830 nm. The instrument has line mapping capability which allows 20 times faster data acquisition. The Raman is coupled to a Quanta FEI SEM (EMU unit) via a Structural Chemical Analyser (SCA) which allows the user to collect SEM images and Raman (514/785 nm) data from the same area of a sample which is located within the SEM chamber. There is also limited photoluminescent and cathodoluminescent capabilities; FTIR Spectrometer with a high throughput screening module (Bruker Tensor 27/HTSXT) an automated system which analyses samples placed onto a 96 well infrared transmissive microtitre plate, primarily used for chacterisation of micro-organisms, but other applications include: analysis of soils and biological fluids. Calorimeters - Capabilities for titrations of solution reactions. Crystal Growth - Optical floating-zone image furnace manufactured by Crystal Systems Inc. Four-mirror design, top temperature of 2200 OC, vacuum and pressure (controlled mixture of 3 gases) capabilities. Electroacoustics - AcoustoSizer-II for analysis of sizes and charges of colloidal particles and ZetaProbe for zeta potential measurements. Electrochemistry - A range of electrochemical techniques, including: microelectrode, rapid scanning, and digital simulation techniques for polarography and voltammetry; bulk electrolysis and electrochemical synthesis (including BAS100B/W and PAR Potentiostat Model 273A instruments); spectroelectrochemical techniques (Electronic, EPR, FTIR, Raman, SERS, XAS); selective electrodes and oxygen sensors. Electronic Absorption and Emission Spectroscopy - Various Cary instruments, including a Cary 5E system with UV/Vis and NIR optical fibre and diffuse reflectance capabilities; Hewlett-Packard Diode Array spectrometer; Emission spectrometers. Electron Microscopy - Many researchers have access and experience with the advanced instrumentation in the Electron Microscopy Unit of the University of Sydney. EPR Spectroscopy - 2 x Bruker EMX, and a Bruker Elexsys E 500 (updated to-state-of-the-art in 2002/2003), X-band, Q-band, L-band, ENDOR, fast scan, liquid He cryostat in a joint facility with UNSW. Gas Sorption - Hiden Isochema IGA-002: gravimetric measurement of the adsorption isotherms for gases and liquid vapours, equipped for measurements up to 10 atm and at high temperature. Quantachrome Autosorb-1 (shared instrument located at Chemical Engineering): volumetric measurement of gas adsorption isotherms at 77 K. High Pressure Equipment - Capable of solution phase synthesis of 2 x 5 mL samples at up to 8,000 atm and 100°C. Key Center for Polymer Colloids - Multidimensional HPLC for polymers, multiple detection size exclusion chromatography (SEC, refractometer, UV, light scattering, Ubbelohde Glass Capillary Viscometer, Membrane Osmometry, NMR Spectroscopy - Bruker 600 MHz, 2 x 400 MHz, 1 x 300 MHz, 1 x 200 MHz spectrometers, plus modern data manipulation and plotting stations. Potentiometric Equipment - For accurate determinations of metal-complex stability constants. Scanning Probe Microscopy - Pico+ SPM (shared with EMU) for use in Atomic Force Microscopy, Conducting Atomic Force Microscopy, Single-Molecule Condctivity, and Scannelling-Tunnelling Microscopy. Separations - Large range of equipment including GC’s, HPLCs, EPLC, Dionex, gel electrophoresis, etc. Stopped-Flow Spectrometers - Applied Photophysics SMV-17, UV/Vis, CD and emission detection, global analysis software; Hi-Tech Scientific SF-61, UV/Vis and emission detection. Surface Analysis Facility (shared with UNSW) - Large range of surface techniques, XPS, Auger spectroscopy, PIXE etc. Surface Characterisation - Atomic force microscopy, neutron reflectometry, small-angle x-ray and neutron scattering. Synthesis - Diverse range of specialist equipment and laboratories for inorganic, organic, organometallic and polymer chemistry. Thermogravimetric Analysis - TGA and modulated DSC; intelligent gravimetric analyser. Two-Photon Spectroscopy - Microprobe fluorescence imaging of biological samples (joint with EMU). 110 School of Chemistry Ultracentrifuge - Is used to separate polymers from supernatant in a polymer colloid, so that the polymer properties can be examined. Vibrational Spectroscopy - Dispersive Raman spectrometer (Jobin-Yvon U1000, Ar+ ion and Kr+ lasers); FT-Raman spectrometer (Bruker RFS100) with 90° and 180° sampling. The FT-Raman is coupled via fibre optic probe to a microscope with 7x7 mm mapping resolution; Renishaw Raman Systems 2000 spectrometer equipped with a 3-axis motorised stage with ±1 mm repeatability. The instrument is capable of point spectroscopy, 2-D Raman imaging and 3-D Raman mapping with 1-5 mm spatial resolution. The Renishaw Raman can use any of the following excitation lines: 488, 514, 532, 567, 647, 752 nm; access to UV Renishaw Raman at Macquarie University with microprobe which has 325, 406 and 442 nm excitation lines; FTIR Spectrometer (Bruker IFS66v) with DRIFT, ATR (single bounce diamond), grazing angle and photoacoustic accessories. The instrument is also equipped with a microscope with an MCT detector and has NIR, MIR and FIR capabilities. X-ray Absorption Spectroscopy - Access to various synchrotron radiation sources for XANES and XAFS analysis, microprobe and stopped-flow techniques on a project specific basis. X-ray and Neutron Powder Diffraction - Benchtop and synchrotron X-ray instruments and access to ANSTO and overseas neutron sources on a project-specific basis; high temperature (1600 °C) capabilities. X-ray, Single-Crystal Diffraction - Bruker SMART 1000 and an imminent installation of a Bruker-Nonius APEX II FR591 high flux and sensitivity system. Oxford Cryosystems cryostats for data collections between 230 deg C and –250 deg C. Microscopes for crystal and micro-crystal examination and manipulation. Access to diffraction facilities at synchrotrons such as the ChemMatCARS facility at the Advanced Photon Source and the European Synchrotron Radiation Facility. Research Publications 112 School of Chemistry Book Chapters 1. 2. 3. Bilic, A, Reimers, JR, Hush, NS. Functionalization of semiconductor surfaces by organic layers: Concerted cycloaddition versus stepwise free-radical reaction mechanisms. Properties of Single Organic Molecules on Crystal Surfaces, 1, Imperial College Press, ISBN: 1-86094-628-3, 1-430, 2006. Larsen, J, Brüggemann, B, Polívka, T, Sly, J, Crossley, MJ, Sundström, V and Åkesson, E. Energy transfer dynamics in Zn-porphyrin-appended dendrimers, in Femtochemistry VII: Fundamental ultrafast processes in chemistry, physics, and biology. Ed. A. Welford Castleman, Jr., Elsevier: Amsterdam, ISBN: 978-0-444-52821-6, 113-116, 2006. Maschmeyer, T and Van De Water, LG. An overview of zeolite, zeotype and mesoporous solids chemistry: Design, Synthesis and Catalytic Properties. Catalysts for Fine Chemical Synthesis, 4, John Wiley & Sons Ltd, ISBN: 0471-49054-7, 1-38, 2006. Annual Research Report 113 Journal Publications 1. Abdullah, A, Huq, F, Chowdhury, A, Tayyem, H, Beale, P and Fisher, K. Studies on the synthesis characterization binding with DNA and activities of two cis-planaramineplatinum(II) complexes of the form: cis-PtL(NH3)Cl2 where L = 3-hydroxypyridine and 2,3-diaminopyridine. BMC Chemical Biology, 6, 1-9, 2006. 2. Alderden, RA, Hall, MD and Hambley, TW. The discovery and development of cisplatin. Journal of Chemical Education, 83, 728-734, 2006. 3. Alderden, RA, Mellor, HR, Modok, S, Hambley, TW and Callaghan, R. Cytotoxic efficacy of an anthraquinone linked platinum anticancer drug. Biochemical Pharmacology, 71, 1136-1145, 2006. 4. Allen, CR, Richard, PL, Ward, AJ, van de Water, LGA, Masters, AF and Maschmeyer, T. Facile synthesis of ionic liquids possessing chiral carboxylates. Tetrahedron Letters, 47, 7367-7370, 2006. 5. Allwood, AC, Walter, MR and Marshall, CP. Raman spectroscopy reveals thermal palaeoenvironments of c.3.5 billion-year-old organic matter. Vibrational Spectroscopy, 41, 190-197, 2006. 6. Allwood, AC, Walter, MR, Kamber, BS, Marshall, CP and Burch, IW. Stromatolite reef from the Early Archaean era of Australia. Nature, 441, 714-718, 2006. 7. Amoore, JJM, Kepert, CJ, Cashion, JD, Moubaraki, B, Neville, SM and Murray, KS. Structural and magnetic resolution of a two-step full spin-crossover transition in a dinuclear iron(II) pyridyl-bridged compound. Chemistry – A European Journal, 12, 8220-8227, 2006. 8. Amoroso, S, Agon, VV, Starke-Peterkovic, T, McLeod, MD, Apell, H-J, Sebban, P and Clarke, RJ. 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Waern, JB, Turner, P and Harding, P. Synthesis and hydrolysis of thiol derivatives of molybdocene dichloride incorporating electron-withdrawing substituents. Organometallics, 25, 3417-3421, 2006. 235. Ward, AJ, Burger, M, Aquino, C, Clegg, JK, Turner, P, Masters, AF and Maschmeyer, T. Bis(2,2´,2˝nitrilotriethanol)cobalt(II) bis(acetate). Acta Crystallographica Section E-Structure Reports Online, E62, m2429m2431, 2006. 236. Ward, RM, Gao, Q, de Bruyn, H, Gilbert, RG and Fitzgerald, MA. Improved methods for the structural analysis of the amylose-rich fraction from rice flour. Biomacromolecules, 7, 866-876, 2006. 237. Webb, JA and James, JM. Karst evolution of the Nullarbor Plain, Australia. Geological Society of America, Special Paper, 404, 65-78, 2006. 238. Wee, S, Mortimer, A, Moran, D, Wright, A, Barlow, CK, O’Hair, RAJ, Radom, L and Easton, CJ. Gas-phase regiocontrolled generation of charged amino acid and peptide radicals. Chemical Communications, 4233-4235, 2006. 239. Whitby, CP, Djerdjev, AM, Beattie, JK and Warr, GG. Nanoparticle adsorption and stabilisation of surfactantfree emulsions. Journal of Colloid and Interface Science, 301, 342-345, 2006. 240. Whitten, A, Turner, P, Klooster, WT, Piltz, RO and Spackman, MA. Reassessment of large dipole moment enhancements in crystals: A detailed experimental and theoretical charge density analysis of 2-methyl-4nitroaniline. Journal of Physical Chemistry A, 110, 8763-8776, 2006. 241. Wichmann, K, Antonioli, B, Söhnel, T, Wenzel, M, Gloe, K, Gloe, K, Price, JR, Lindoy, LF, Blake, AJ and Schröder, M. Polyamine-based anion receptors: Extraction and structural studies. Coordination Chemistry Reviews, 250, 2987-3003, 2006. 242. Widmer-Cooper, A and Harrowell, P. Free volume cannot explain the spatial heterogeneity of Debye–Waller factors in a glass-forming binary alloy. Journal of Non-crystalline Solids, 352, 5098-5102, 2006. 243. Widmer-Cooper, A and Harrowell, P. Predicting the long-time dynamic heterogeneity in a supercooled liquid on the basis of short-time heterogeneities. Physical Review Letters, 96, 185701, 2006. 244. Willis, AC, O’Connor, PD, Taylor, WC and Mander, LN. The absolute stereochemistry of the Galbulimima alkaloids. Australian Journal of Chemistry, 59, 629-632, 2006. 245. Winkelman, GB, Dwyer, C, Marsh, C, Hudson, TS, Nguyen-Manh, D, Doblinger, M and Cockayne, DJH. The crystal/glass interface in doped Si3N4. Materials Science & Engineering, A: Structural Materials: Properties, Microstructure and Processing, A422 (1-2), 77-84, 2006. 246. Wittick, LM, Jones, LF, Jensen, P, Moubaraki, B, Spiccia, L, Berry, KJ and Murray, KS. New mixed-valence MnII2MnIII2 clusters exhibiting an unprecedented MnII/III oxidation state distribution in their magnetically coupled cores. Dalton Transactions, (12), 1534-1543, 2006. 126 School of Chemistry Annual Research Report 127 247. Witting, PK, Harris, HH, Rayner, BS, Aitken, JB, Dillon, CT, Stocker, R, Lai, B, Cai, Z and Lay, PA. The endothelium-derived hyperpolarizing factor H2O2, promotes metal-ion efflux in aortic endothelial cells: Elemental mapping by a hard x-ray microprobe. Biochemistry, 45, 12500-12509, 2006. Conference Publications 248. Wood, GPF, Easton, CJ, Rauk, A, Davies, MJ and Radom, L. Effect of side chains on competing pathways for b-scission reactions of peptide-backbone alkoxyl radicals. Journal of Physical Chemistry A, 110, 10316-10323, 2006. Refereed 249. Wood, GPF, Radom, L, Petersson, GA, Barnes, EC, Frisch, MJ and Montgomery (Jr), JA. A restricted-open-shell complete-basis-set model chemistry. Journal of Chemical Physics, 125, 94106, 2006. ~ ~ 250. Yin, H-M and Kable, SH. Rotational analysis of the HCO B(2A´ ) – X(2A´ )311 and 312 bands. Journal of Molecular Spectroscopy, 237, 163-173, 2006. 1. Brooker, L, Goebel, C, Kazlauskas, R, Trout, G and George, AV. Confirmation of Triamcinolone Acetonide Use by LC-MS-MS. Recent Advances in Doping Analysis (14). Proceedings of the Manfred Donike Workshop, 24th Cologne Workshop on Dope Analysis, 4th to 9th June 2006, p463-466, Koln: Sportverlag Strauss. Ed: W. Schanzer, H. Geyer, A. Gotzmann, U. Mareck. ISBN: 978-3-939390-14-5. 251. Yin, HM, Kable, SH, Zhang, X and Bowman, JM. Signatures of H2CO photodissociation from two electronic states. Science, 311, 1443-1446, 2006. 2. Cawley, A, Kazlauskas, R, Trou, G, Tjoa, J, Huynh, T and George, AV. GC-C-IRMS Analysis of Endogenous Reference Compounds. “Recent Advances in Doping Analysis (14)”. Proceedings of the Manfred Donike Workshop, 24th Cologne Workshop on Dope Analysis, 4th to 9th June 2006, p267-276, Koln: Sportverlag Strauss. Ed: W. Schanzer, H. Geyer, A. Gotzmann, U. Mareck. ISBN: 978-3-939390-14-5. 3. Fernandez, JR and Harrowell, P. What stabilizes the intermediate structure of an amorphous alloy? AIP Conference Proceedings, Flow Dynamics, 832, 3-10, 2006. 4. Marshall, CP. Special issue - A collection of papers presented at 6th Australian Conference on Vibrational Spectroscopy (ACOVS 6) - Sydney, Australia - 28-30 September, 2005 - Preface. Vibrational Spectroscopy, 41, 143-143, 2006. 5. Noren, L, Christensen, J, Lidin, S, Schmid, S and Withers, RL. The Sn1-xSb1+x, x ~ 0.5, Solid Solution: The Relationship Between a and b. 30th Annual Condensed Matter and Materials Meeting, 7-10 February, 2006, Wagga Wagga, Australia. Australian Institute of Physics, ISBN: 1-920791-09-4, 1-3, 2006. 256. Zhou, Q, Kennedy, BJ and Elcombe, MM. Synthesis and structural studies of cation-substituted Aurivillius phases ASrBi2Nb2TiO12. Journal of Solid State Chemistry, 179, 3744-3750, 2006. 6. 257. Zhu, H, Zheng, Z, Gao, X, Huang, Y, Yan, Z, Zou, J, Yin, H, Zou, Q, Kable, SH, Zhao, J, Xi, Y, Martens, WN and Frost, RL. Structural evolution in a hydrothermal reaction between Nb2O5 and NaOH solution: From Nb2O5 grains to microporous Na2Nb2O6 · 2/3H2O fibers and NaNbO3 cubes. Journal of the American Chemical Society, 128, 2373-2384, 2006. Pecchia, A, Gagliardi, A, Solomon, G, Di Carlo, A, Frauenheim, Th and Reimers, JR. Incoherent tunneling and heat dissipation in molecular bridges. Progress in Nonequilibrium Green’s Functions III, August 22-25, 2005. Journal of Physics: Conference Series. Institute of Physics Publishing, 35, 349-356, 2006. 7. Read, JR, Buntine, MA, Crisp, GT, Barrie, SC, George, AV, Kable, SH, Bucat, RB and Jamie, IM. The ACELL project: Student participation, professional development, and improving laboratory learning. Symposium Proceedings: Assessment in Science and Learning, September 28, 2006, The University of Sydney, Australia, 113-119, 2006. 258. Ziolkowski, EJ, Turner, P and Rendina, LM. Mono- and di-nuclear platinum(II) complexes containing O- and N-bonded acetamide. Inorganic Chemistry Communications, 9, 53-56, 2006. 8. Schmid, SA, Elcombe, M and Rhode, M. Defect perovskites in the SrO-ZrO2Nb2O5 system. 30th Annual Condensed Matter and Materials Meeting, 7-10 February, 2006, Wagga Wagga, Australia. Australian Institute of Physics, ISBN: 1-920791-09-4, 1-3, 2006. 9. Yeung, A, George, A, Schmid, S and King, M. Testing the personalisation hypothesis in pre-laboratory e-learning environments. Symposium Proceedings: Assessment in Science and Learning, September 28, 2006, The University of Sydney, Australia, 146-152, 2006. 252. Yuen, AKL, Jolliffe, KA and Hutton, CA. Preparation of the central tryptophan moiety of the celogentin/moroidin family of anti-mitotic cyclic peptides. Australian Journal of Chemistry, 59, 819-826, 2006. 253. Zhou, Q and Kennedy, BJ. The nature of the orthorhombic to tetragonal phase transition in Sr1-xCaxMnO3. Journal of Solid State Chemistry, 179, 3568-3574, 2006. 254. Zhou, Q and Kennedy, BJ. Thermal expansion and structure of orthorhombic CaMnO3. Journal of Physics and Chemistry of Solids, 67, 1595-1598, 2006. 255. Zhou, Q, Kennedy, BJ and Elcombe, MM. Neutron powder diffraction studies of Ca2-xSrxCoWO6 double perovskites. Physica B, 385-386, 190-192, 2006. 10. Youl, DJ, Read, JR, George, AV and Schmid, S. Bridging courses: Good learning environments for engaging students? Engaging Students, 12-14 July, Gold Coast, QLD, Australia. Published by Queensland University of Technology. ISBN: 0-646-46313-6, 1-11, 2006. 128 School of Chemistry 129 Annual Research Report Patents 1. Max Crossley, Pall Thordarson, Neil Hunter, Benjamin Yap, and Charles Andrew Collyer, Porphyrin Linked Metronidazole for Treatment of Gum Disease Caused by Porphyromonas Gingivalis. PCT Int. Appl. W02006005137, A1 20060119; CAN 144:128797; AN 2006:54402 85 pp. 19th January 2006. International Classification: (IPC1-7): C07D403/14 2. Bis-pyridinium compounds. K. Jolliffe, A. Widmer, Australian Provisional Patent, Application no. 2006902367, The University of Sydney. 3. C.J. Kepert, M.E.R. Green; Indicator, Australian Provisional Patent, Application No. 2006904033, the University of Sydney (2006). 4. Lay, Peter; Hambley, Trevor; Kennedy, Brendan; Morgan, Ying. Preparation of copper indomethacin complexes having antiinflammatory activity. PCT Int. Appl. (2006), 80pp. WO 2006099684 5. Lay, Peter; Hambley, Trevor; Kennedy, Brendan; Morgan, Ying; Kaur, Ravinder; Davies, Neal. Preparation of transition metal acemetacin complexes with antiinflammatory activity. PCT Int. Appl. (2006), 69pp. WO 2006099677 6. Lay, Peter; Hambley, Trevor; Kennedy, Brenden; Davies, Neal. Method for the prophylaxis or treatment of carcinomas using metal complexes of antiinflammatory drugs. PCT Int. Appl. (2006), 132pp. WO 2006099685 7. Lay, Peter; Methods and compositions for the prophylaxis or treatment of cancers of the skin, PCT/IB2006/002423, 01/09/06 8. Lay, Peter; Hambley, Trevor, Methods for prophylaxis or treatment of cardiovascular inflammation, Provisional patent applications, Aus 2006901557, 27/03/06; USA, 60/830,203, 11/07/06 9. Lay, Peter; Hambley, Trevor, Methods for prophylaxis or treatment, Provisional patent applications, Aus 2006901583, 28/03/06; USA, 11/07/06 10. Lay, Peter, Hambley, Trevor, Metal complexes having anti-inflammatory activity, Provisional patent applications, Aus 2006905170, 19/09/06; Aus 2006905267, 22/09/06; Aus 2006905377, 28/09/06. 11. Lay, Peter, Hambley, Trevor, Prophylaxis and treatment of cancer. Provisional patent application, Aus 2006905259, 22/09/06 12. Lay, Peter, Hambley, Trevor, Combination Therapy for the Treatment of Cancer. Provisional patent application, Aus 2006905260, 22/09/06. 13. Lay, Peter, Hambley, Trevor, Metal complexes having anti-inflammatory activity II, Provisional patent applications, Aus 2006905265, 22/09/06; Aus 2006905378, 28/09/06 14. Lay, Peter, Hambley, Trevor, Skin treatment and wound repair. Provisional patent application, Aus 2006905266, 22/09/06. 15. Maschmeyer, T., Fois, A., Masters, A.F., COmpartmentlaised Nanoreactors, Provisional Application US Patent Office: Filed on 25 August 2006, United States of America Patent Application No. 60/840009. 16. Shan, Z., Jansen, J. C., Yeh, C. Y., Angevine, P. J., Maschmeyer, T. & Hamdy, M. S., Mesoporous metal oxide-based supports and catalysts for petroleum refining and conversion of organic compounds, 2005-198564 2006052234, ((USA).), 34 pp , Cont -in-part of U S Ser No 313,720 2006. 17. Vesiculated Polymer Particles, Australian Provisional Patent number 12844010, October 2006. 2005 Total Book Chapters Journal Publications Conference Papers Patents 5 224 18 7 2006 Total Book Chapters Journal Publications Conference Papers Patents 3 258 10 17 Research Fellowships & Grants 132 School of Chemistry Fellowships Annual Research Report 133 ARC Grants Discovery Projects Dr Rob Atkin ARC Australian Postdoctoral Fellowship Professor Jeffrey Reimers ARC Professorial Fellowship Associate Professor Phil Attard ARC Australian Professorial Fellowship Dr Pall Thordarson ARC Australian Research Fellowship Dr Gregory Giles University of Sydney Postdoctoral Fellowship Dr Catherine Whitby Gritton Postdoctoral Fellowship Dr Angus Gray-Weale ARC Australian Postdoctoral Fellowship Dr Hugh Harris ASRP Postdoctoral Fellowship Dr Toby Hudson University Postdoctoral Research Fellowship Dr Kate Jolliffe ARC Queen Elizabeth II Fellowship Dr Meredith Jordan ARC Australian Research Fellowship Professor Cameron Kepert ARC Federation Fellowship Professor Peter Lay ARC Australian Professorial Fellowship Dr Nigel Lucas ARC Australian Postdoctoral Fellowship Dr Craig Marshall ARC Australian Postdoctoral Fellowship Professor Thomas Maschmeyer ARC Federation Fellowship Dr Damian Moran Sesqui Postdoctoral Fellowship Dr Klaas Nauta ARC Australian Research Fellowship Professor Leo Radom ARC Australian Professorial Fellowship Nanotribology and nanorehometry: A fundamental study of the dynamic interactions of particles and surfaces at the molecular level Attard, P – $160,934 The interface of oil-in-water emulsions Beattie, JK, Warr, GG – $95,827 Anti-cancer natural products: Total synthesis and biological evaluation of lasonolide A and analogues Coster, MJ – $114,444 Design and development of HIV-1 integrase inhibitors based on a natural product lead Coster, MJ – $55,232 Molecular electronics: From electron transfer through photosynthesis towards functional nano devices Crossley, MJ, Reimers, JR, Hush, NS – $301,103 Organometallic transformations of organic molecules Field, LD – $90,198 Reactions of coordinated dinitrogen Field, LD, Messerle, BA – $103,931 Formation and stability of polymerically stabilized colloids Gilbert, RG – $99,641 Molecular archaeology: New knowledge from molecular weight distributions of synthetic and natural polymers Gilbert, RG – $197,686 Disorder and dynamics in superionic conductors Gray-Weale, A – $75,907 Probing and developing hypoxia-selective anti-cancer agents Hambley, TW – $85,179 Functionalised MMP inhibitors as radiodiagnostic, radiotherapeutic, and radiation-sensitising agents for metastatic cancer Hambley, TW, Kassiou, M – $93,748 Antifreeze proteins and glycoproteins Harding, MM, Haymet, ADJ – $8,992 Synthesis and applications of antifreeze proteins and glycoproteins Harding, MM – $140,000 The stability of glass-forming alloys: simulation studies Harrowell, PR – $74,532 134 School of Chemistry 135 Annual Research Report Backbone modified cyclic peptides: Scaffolds for supramolecular chemistry Jolliffe, KA – $11,152 Elucidating the mode of action of nicotinic receptor ligands McLeod, MD – $96,805 Cross-linked Tyrosine Residues in Peptides and Proteins Jolliffe, KA, Hutton, CA – $1,597 Superfluid helium nanodroplets: A unique matrix for molecular spectroscopy Nauta, K – $130,698 Self-assembly of nanoscale molecular capsules Jolliffe, KA, Lindoy, LF – $135,252 Free radicals in chemistry and biology: A computational quantum chemistry investigation Radom, L – $91,425 Predicting environmental effects on structure and reactivity Jordan, MJT – $62,424 Molecular electronics principles and applications Reimers, JR – $232,947 The first chemically accurate tools in theoretical materials research Jordan, MJT – $105,818 Platinum-carborane complexes as new agents for boron neutron capture therapy Rendina, LM – $93,636 Understanding phase transitions through precise structural studies Kennedy, BJ, Siegbert, SA – $77,474 DNA nanoshuttles: A new class of DNA-binding molecules Rendina, LM, Harding, MM – $128,964 Polynuclear spin-crossover molecular switches: Host-guest chemistry magnetism and memory Kepert, CJ – $96,237 Laser spectroscopy of molecular electronic components Schmidt, T – $152,850 Molecular framework materials: Nanoporosity and anomalous thermal expansion Kepert, CJ – $150,812 Optical spectroscopy of extraterrestrial molecules Schmidt, T – $136,546 The chemistry and biochemistry of chromium: Cancer and nutrition Lay, PA – $144,976 Light-activated bioconjugates for application in synthesis and biosensors Thordarson, P – $242,788 Nanoprobe and microprobe structural and spectroscopic studies in biomedical research Lay, PA, Harris, HH, Stampfl, AP – $127,375 Surfactant self-assembly in ionic liquids Warr, GG, Atkin, R – $97, 755 Metal directed assembly of new supramolecular systems Lindoy, LF, Meehan, GV – $86,900 Platinum-group metal oxides with modulated crystal structures: Flexible frameworks designed for geometrically frustrated magnetism Ling, Dr CD – $81,520 Metallographitic discs as new materials Lucas, N – $125,328 Organic geochemistry of the McArthur River hydrothermal deposit Marshall, CP – $94,760 From nanostructured catalysts to process innovation Maschmeyer, T – $156,060 Molecular recognition in chiral ionic liquids Maschmeyer, T – $163,040 Improved catalysts for the liquid phase hydrocarbon oxidation Masters, A, Beattie, JK, Maschmeyer, T – $85,179 Synthesis of the pyrrolo[21-c][14]benzodiazepines: potent DNA binders McLeod, MD – $117,122 TOTAL: $4,924,794 ARC Linkage Projects Synthesis and evaluation of anti-microbial porphyrin adducts for the targeted inhibition of Porphyromonas gingivalis Crossley, MJ, Collyer, C – $73,714 Development of a molecular flash memory for long-term extremely high-capacity unpowered data storage Crossley, MJ, Reimers, JR, Hush, NS, Thordarson, P – $322,513 Novel barrier products: Synthesis design using controlled radical polymerization in dispersed systems Gilbert, RG – $3,189 Rubbery nanoparticles for improved plastics additives and adhesives through novel low-temperature polymerization Gilbert, RG – $48,082 Nanoparticles with designed morphology for surface-coating applications Hawkett, BS, Warr, GG, Gilbert, RG – $322,524 Metal-based anti-inflammatory drugs with high efficacy and low side-effects Lay, PA, Hambley, TW, Pearce S, Dillon, C – $106,506 136 School of Chemistry Supercritical highly-integrated and modular, continuous solid-catalysed biodiesel production from plant and animal feedstocks Maschmeyer, T, Haynes, BS – $78,972 Inception of a practical biomimetic flexible photovoltaic device Reimers, JR, Crossley, MJ, Hush, NS – $252,355 137 Annual Research Report ARC Linkage International Grants Polynuclear spin-crossover molecular switches: Host-guest chemistry, magnetism and memory Kepert, CJ – $7,133 Development of a test bed for molecular memory and molecular photovoltaic devices Reimers, JR – $10,000 Bubble stabilization and density control in self-supporting explosive emulsions Warr, GG, Hawkett, BS, Tanner, RI, Gore, J – $134,067 TOTAL: $1,341,922 Ditopic receptors for the co-operative binding of cations and anions Lindoy, LF – $9,157 Chemistry of the archaean ocean and its impact on Earth’s early atmosphere and ecosystems Rey, PF, Philippot, P, Dutkiewicz, A, Marshall, CP, Van Kranendonk – $133,670 ARC Linkage - Infrastructure Equipment and Facilities (LIEF) Structure of polymer surfactant lubricant layers Warr, GG, Richetti, P – $24,279 LIEF grants are multi-institutional, often involving a large number of researchers. In 2006, members of the School were involved in the following successful LIEF grants:Combinatorial deposition and characterisation facility for new alloy thin film materials Bilek, MM, Valanoor, N, McKenzie, Dr, O’Connor, J, Green, MA, Lay, PA, Ekins-Daukes, NJ, King, BV, James, BW, Conibeer, GJ, Kable, SH, Schmidt, T, Ostrikov, K, Hoffman, MJ, Riley, DP, Ferry, M – $1,200,000 Access for Australian researchers to advanced neutron beam techniques Kennedy, BJ and AINSE – $240,000 TOTAL: $184,239 ARC Special Research Initiative Scientific instruments as ICT components in building a GrEMLIN for e-research Kepert, CJ, Turner, P, Zomaya, A – $62,424 e-Research infrastructure for the molecular and materials structure sciences Kepert, CJ and University of Queensland – $1,000,000 Floating-zone crystal growth facility Ling, CD, Kennedy, BJ, Schmid, SA, Robinson, R, Curfs, C, Welberry, TR, Withers, RL, Stampfl, AP – $210,000 Elemental and structural analysis facility comprising a FTICR mass spectrometer and a CHNS analyser Maschmeyer, T, Lay, PA, Kable, SH, Karuso, PH, Gore, DB, Downard, KM, McLeod, MD, Jolliffe, KA, Johnston, GA, Hanrahan, JR, Fisher, KJ – $730,000 TOTAL: $62,424 ARC Research Network Molecular and materials structure network Kepert, CJ (plus 100 other participants) – $300,000 The rapid kinetics research facility – an integrated system for rapid kinetic studies of materials using synchrotron radiation Maschmeyer, T and The University of Newcastle – $195,000 TOTAL: $300,000 ARC Centres of Excellence Nanostructure deposition facility Reimers, JR and The University of Newcastle – $180,240 Facility for structural analysis of bio-molecular complexes and self assembly Trewhella, J, Curmi, PM, Mabbutt, BC, Warr, GG, Stokes, HW, Cavicchioli, R – $950,000 TOTAL: $4,705,240 Free radical chemistry and biotechnology Radom, L – $392,873 TOTAL: $392,873 138 School of Chemistry 139 Annual Research Report Australian Nuclear Science and Technology Organization (ANSTO) ARC Fellowships Dr Rob Atkin ARC Australian Postdoctoral Fellowship Associate Professor Phil Attard ARC Australian Professorial Fellowship Dr Angus Gray-Weale ARC Australian Postdoctoral Fellowship Access to Major Research Facilities Program Dr Kate Jolliffe ARC Queen Elizabeth II Fellowship Structure of discrete and bicontinuous room-temperature ionic liquid microemulsions Microemulsion structure in some new protic ionic liquid Atkin, R – $10,327 Dr Meredith Jordan ARC Australian Research Fellowship Phase transitions in two double perovskites - K2SnCl6 and K2ReCl6 - Neutron Science Laboratory (KENS), Japan, 21 April 2004 Kennedy, BJ – $12,711 Professor Cameron Kepert ARC Federation Fellowship Isotropic negative thermal expansion in a molecular framework - ISIS facility UK February 2003, 3 days Kepert, CJ – $16,403 Professor Peter Lay ARC Australian Professorial Fellowship Neutron powder diffraction studies of oxygen vacancy ordering in misfit-layered cobaltates Ling, C – $5,953 Dr Nigel Lucas ARC Australian Postdoctoral Fellowship An XAFS study of non-heme iron oxidase mimics Rutledge, PJ – $3,891 Dr Craig Marshall ARC Australian Postdoctoral Fellowship Experiments at ISIS, UK - September 2003 Warr, GG – $11,377 Professor Thomas Maschmeyer ARC Federation Fellowship TOTAL: $60,662 Dr Klaas Nauta ARC Australian Research Fellowship Professor Leo Radom ARC Australian Professorial Fellowship Australian Synchrotron Research Program Professor Jeffrey Reimers ARC Professorial Fellowship Negative thermal expansion in coordination framework materials Kepert, CJ, Halder, Dr Greg – $9,900 Dr Pall Thordarson ARC Australian Research Fellowship Investigations into the rate of biotransformation of inorganic chemotherapeutics - ANBF Hambley, TW – $15,936 TOTAL: $1,801,740 ARC TOTAL: $13,713,232 Biotransformations of chemopreventative selenium compounds in bulk cell cultures - ANBF Harris, HH – $20,036 Structures and phase transitions in metal oxides and halides - ANBF Kennedy, BJ – $22,943 XAFS studies of bioinorganic systems - ANBF and NSRRC Lay, PA – $49,162 140 School of Chemistry 141 Annual Research Report Other External Competitive Grants Travel under the Australian Synchrotron Research Program Ling, CD – $7,363 Ceramic materials with modulated structures - ANBF, Japan, 18-19 November 2003 Schmid, SA – $594 Australian Antarctic Science Grant Molecular characterisation of cold-adapted metallo-oxtransferases from the dimethylsulfoxide reductase family expressed by Antarctic bacteria (Genus: Shewanella) Codd, R – $9,245 Fellowships Dr Hugh Harris ASRP Postdoctoral Fellowship International Joint Research Grants TOTAL: $162,579 Australian Institute of Nuclear Science and Engineering (AINSE) Scholarships and Awards New strategies for developing ultrathin nanostructured polymer films Warr, GG, Gilbert, RG – $33,805 Australian Academy of Technological Sciences and Engineering/ DEST Sydney-SIOC new chemical technologies workshop, Shanghai, China Todd, MH – $32,000 FAST, DEST/French Embassy Self-assembly of diblock copolymers Blom, A – $6,660 Light induced electronic switching in nanoporous materials and supramolecular clusters Kepert, CJ – $16,500 Structure of Bi double perovskites Kennedy, BJ – $20,400 TOTAL: $91,550 Negative thermal expansion in molecular framework materials Kepert, CJ – $7,525 Optimising magnetic frustration: search for a ‘quantum spin-liquid’ state in a variable crystal structure Ling, CD – $44,200 Geometrically frustrated magnetism in bismuth platinum-group oxides Ling, CD – $13,000 Structural studies of ionic conductive defect perovskites Saines, P, Kennedy, BJ – $13,000 Structure of polymerised surfactant films on quartz Warr, GG – $27,415 Ceramic materials with modulated structures Schmid, SA – $32,300 TOTAL: $164,500 142 School of Chemistry University of Sydney Grants 143 Annual Research Report Fellowships Dr Gregory Giles University of Sydney Postdoctoral Fellowship Research and Development Scheme New antibacterial agents effective against methicillin-resistant Staphylococcus Aureus (MRSA) Coster, MJ – $21,000 Misfit-layered cobaltates: Structurally flexible ceramic oxides with tuneable magnetic and electronic properties Ling, CD – $29,000 Dr Toby Hudson University Postdoctoral Research Fellowship Dr Damian Moran Sesqui Postdoctoral Fellowship Dr Catherine Whitby Gritton Postdoctoral Fellowship New catalysts for hydrocarbon oxidation Rutledge, PJ – $21,000 A new chemical route to an important antiparasitic pharmaceutical Todd, MH – $24,000 TOTAL: $786,892 NH&MRC Grants Project Grant Fungal phospholipases: A novel target for drug discovery Jolliffe, KA – $191,950 Equipment Grant New strategies for developing ultrathin nanostructured polymer films Lay, PA – $65,500 Industrial Research Partnerships Codd, R – (Herman Slade Foundation) Crossley, MJ, Reimers, JR, Hush, NS, Thordarson, P – (Research Contract) Gilbert, RG – (BASF) Gilbert, RG – (Research Contract) Gilbert, RG, Hawkett, BS – (Ansell Shah Alam Sdn Bhd) Cancer Research Fund Grants Synthesis and biological evaluation of new anti-mitotic anti-cancer compounds based on a highly cytotoxic natural product Coster, MJ – $49,737 Tumour specific boronated peptides as a new class of agents for boron neutron capture therapy Rendina, LM, Jolliffe, KA – $49,885 A new class of DNA-cleaving artificial enzymes Todd, MH– $49,888 Harrowell, PR – (AOARD-US Air Force) Hawkett, BS – (Sirtext Medical Ltd) Hawkett, BS – (Kerr-McGee Chemical) Hawkett, BS, Warr, GG, Gilbert, RG – (Research Contract) Kepert, CJ – (UCOM Ten) Kepert, CJ – (DEST) Lay, PA, Hambley, TW – (Medical Therapies Ltd) Lay, PA, Hambley, TW, Pearce, S, Dillon, C – (Nature Vet Pty Ltd) Maschmeyer, T – (CSIRO Flagship Collaboration Research Fund) Ridley, D, Stamford, NP – (Silverbrook Research Pty Ltd) Stamford, NP – (NSW Department of Primary Industries (through Yanco Agricultural Institute)) Stamford, NP – (Ultraceuticals Pty Ltd) Bridging Support Grants Redox enzymes from Antarctic organisms Codd, R – $26,300 Turner, P – (Grangenet) Vonwiller, S – (Research Contract) TOTAL: $ 1,810,448 144 School of Chemistry Bequests 145 Annual Research Report The Cornforth Foundation for Chemistry Bae, Ms Carol Bellas, Dr Thomas Cannon, Dr Jack Ridley, Dr Anne Agnes Campbell Bequest Bruce Veness Chandler Bequest Professor Archibald Liversidge Bequest Scholfield Bequest RJW Le Fèvre Bequest GG Blake Radio Research Bequest Janet Elspeth Crawford Bequest Charles E Fawsitt Bequest Edna Maude Goulston Bequest Arthur Hollis Memorial Prize George Harris Scholarship CH Wilson Prize Dr Joan R Clark Research Scholarship John A Lamberton Research Scholarship Surface Coating Association of Australia Scholarship The Gritton Scholarships The Hush Trust Lim, Associate Professor Kieran TOTAL: $4,525 TOTAL: $589,359 Other Donations The School of Chemistry would like to thank the following people for their generous donations during 2006:- The School of Chemistry Alumni Fund Broadhurst, Associate Professor Norman Petfield, Mr Gregory The Foundation for Inorganic Chemistry Alpha Chemicals Pty Ltd Barlow, Dr Thomas Freeman, Emeritus Professor Hans Geyer, Mr Robert Huq, Dr Fazlul Lay, Professor Peter Lindoy, Emeritus Professor Len Nell & Herman Slade Trust Savage, Mr Thomas Total Income for 2006 $17,383,747 146 School of Chemistry Awards, Scholarships & Prizes 148 School of Chemistry Annual Research Report 149 Awards to Staff Ms Katie Cergol, PhD Student Jim O’Donnell Travel Award from the RACI. Dr Mark Coster RACI Organic Division Lectureship for Recently Appointed Staff. Mr Malcolm Green, PhD Student Shared the Grand Prize in the University of Sydney Innovation Challenge competition for his business plan on the applications of nanotubular clays. Malcolm’s was judged the equal top from more than 400 entries received across the entire University. The prize, amounting to $20,000, is to be directed towards the commercialisation of his research. Dr Deanna D’Alessandro Cornforth Medal of the RACI for the most outstanding PhD thesis submitted in any branch of chemistry, chemical science or chemical technology. Dr Brian Hawkett Citation by the RACI Polymer Division at the 28th Australasian Polymer Symposium in Rotorua. This award recognises Brian’s scientific achievement in the study of emulsion polymerization and for services to the Polymer Division. Dr Kate Jolliffe RACI’s Biota Award for her work on Inhibitors of Fungal Phospholipase B: Novel Antifungal Agents. The Medal is awarded to the chemist judged to be responsible for the best drug design and development paper published, patent taken out, or commerical-in-confidence report in the previous calendar year concerning small molecules (less than 1,000 Da) as potential therapeutic agents. Professor Cameron Kepert Inaugural Alan Sargeson Award. This award has allowed Cameron to visit and talk at chemistry departments around the country during 2006. Emeritus Professor Len Lindoy Mercator Guest Professorship at the Technical University Dresden for a period of five months. Professor Leo Radom Fukui Medal. The senior medal of the Asian Pacific Association of Theoretical and Computation Chemists. Awards to Students Ms Kaitlin Beare, PhD Student Best poster presentation at the RACI Drug Design Conference. This is a high profile conference attended by leading academic and industrial medicinal chemistry groups within Australia. Mr David Bray, PhD Student C.G. and R.J.W. Le Fèvre Postgraduate Student Lectures Award. These lectures were established in 1985 following a gift of $2 000 from Emeritus Professor R.J.W. Le Fèvre and are awarded on the recommendation of the Sydney University Chemical Society. Mr Lance Brooker, PhD Student The Chromatography Prize. This prize was presented at the 14th Annual RACI R&D Topics Conference, 5th to 8th December 2006 at Wollongong University. Mr Peter Brotherhood, PhD Student C.G. and R.J.W. Le Fèvre Postgraduate Student Lectures Award. These lectures were established in 1985 following a gift of $2 000 from Emeritus Professor R.J.W. Le Fèvre and are awarded on the recommendation of the Sydney University Chemical Society. Ms Annie Nguyen, Honours Students NSW RACI Analytical Chemistry Award Mr Joshua Peterson, PhD Student Best Oral Presentation at the RACI NSW Organic Chemistry Group One Day Symposium at the RSC, ANU on the 27th November, 2006. Mr Nima Sayyadi, PhD Student Best Poster Presentation at the RACI NSW Organic Chemistry Group One Day Symposium at the RSC, ANU on the 27th November, 2006. Ms Natasha Sciortino, PhD Student Ludo Crystallography Scholarship by the International Centre for Diffraction Data (ICDD). Only six of these are awarded each year. Mr Stuart Thickett, PhD Student 1. C.G. and R.J.W. Le Fèvre Postgraduate Student Lectures Award. These lectures were established in 1985 following a gift of $2 000 from Emeritus Professor R.J.W. Le Fèvre and are awarded on the recommendation of the Sydney University Chemical Society. 2. NSW Student RACI Polymer Prize. Mr Shane Wilkinson, PhD Student Best oral presentation at the RACI Drug Design Conference. This is a high profile conference attended by leading academic and industrial medicinal chemistry groups within Australia. Ms Alexandra Yeung, PhD Student Jim O’Donnell Travel Award from the RACI. 150 School of Chemistry Student Prizes and Scholarships T he School of Chemistry awards over $85 000 in Prizes and Scholarships each year to the best of its students. The following students were awarded prizes or scholarships in 2007 based on their academic achievements in 2006. Scholarships are awarded subject to the students satisfying conditions required for each of the individual scholarships. Agnes Campbell Prize Postgraduates Samuel Banister Kaitlin Beare David Bray Peter Brotherhood Katie Cergol Jack Clegg Joshua Fischer Hendra Gunosewoyo Jill Halliday Tony Khoury Rebecca Lesic Daniel Obando Gutierrez Joshua Peterson Shiva Prasad Nima Sayyadi David Schilter Erin Sheridan (Ziolkowski) Grace Simpkins Maxine Sintic Danial Stocks Cody Szczepina James Webb Shane Wilkinson Tomasz Wyczesany Benjamin Yap Agnes Campbell Prize Honours Hong Yue Ching James Cochrane John Nguyen Doan Alessandro Fois Adam Hambly Joseph Ioppolo Wing Yan Leung Iman Moussa Adam Piggott Katie Tong Shane Wilkinson Philip Young Arthur Hollis Memorial Prize Nithin Iyer Australian-USA Foundation Prize Kathryn Gall Charles E. Fawsitt Prize Amelia Parker Joan R Clark Research Scholarship Jarrod Amoore Cindy Aquino Jack Clegg Jeannette McAlpine Mark Roberston Natasha Sciortino Benjamin Yap Chemistry Alumni Scholarship Jill Halliday Levey Scholarship 2 Yu Heng Lau Edna Maude Goulston Prize in Organic Chemistry (shared) Rhiannon Stewart Shane Wilkinson Levey Scholarship 3 David Llewellyn C.H. Wilson Prize Adam Pigott Frank E. Dixon Scholarship George Zhong G.S. Caird Scholarship (3 awards) Patricia Donovan Jenna Joester Jessica Veliscek Carolan G e o rg e H a r r i s S c h o l a r s h i p (shared) Rebecca Lesic Jeannette McAlpine Joshua Peterson Hush Prize Oliver Thorn-Seshold Inglis Hudson Scholarship (3 awards) William Early Michael Lee Belinda Lu Iredale Prize Cameron Weber Janet Elspeth Crawford Prize in Chemistry Natsuho Yamamoto R.J.W. Le Fèvre – DAASN RAO Prize Jenna Joester R.J.W. Le Fèvre Research Travelling Scholarship Erin Sheridan Slade Prize Alexandra Manos-Turvey Surface Coating Association of Australia Scholarship Stuart Thickett Walter Burfitt Scholarship No.1 Oliver Thorn-Seshold 2006 Staff and Students 152 Academic Staff Head of School HAMBLEY, Prof Trevor Deputy Head of School WARR, Prof Greg School of Chemistry Annual Research Report MASCHMEYER, Prof Thomas MASTERS, A/Prof Tony McLEOD, Dr Mal RENDINA, Dr Lou RUTLEDGE, Dr Peter SCHMID, Dr Siggi SCHMIDT, Dr Timothy TODD, Dr Mat WARR, Prof Greg Head of Research KENNEDY, A/Prof Brendan Head of Teaching BAKER, Dr Rob 1st Year Coordinator SCHMID, Dr Siggi 2nd Year Coordinator CLARKE, Dr Ron 3rd Year Coordinator BAKER, Dr Rob Honours RENDINA, Dr Lou (Director) SCHMIDT, Dr Timothy (Coordinator) Postgraduate Studies KENNEDY, A/Prof Brendan (Director) COSTER, Dr Mark (Coordinator) BAKER, Dr Rob BEATTIE, A/Prof James CLARKE, Dr Ron CODD, Dr Rachel COSTER, Dr Mark CROSSLEY, Prof Max GEORGE, Dr Adrian GILBERT, Prof Bob HAMBLEY, Prof Trevor HARROWELL, Prof Peter HUNGERFORD, Dr Natasha JORDAN, Dr Meredith KABLE, A/Prof Scott KASSIOU, A/Prof Michael KENNEDY, A/Prof Brendan KEPERT, Prof Cameron LACEY, Dr Tony LAY, Prof Peter LINDOY, E/Prof Len LING, Dr Christopher Academic - Research Staff ATKIN, Dr Rob YUEN, Mr Alex ATTARD, A/Prof. Phil BLAKE, Dr Iain BOBILLIER, Ms Sophie BONIN, Dr Antonio CAI, Dr Zheng-Li CASTIGNOLLES, Dr Patrice CHOW, Dr Hoi Shan D’ALESSANDRO, Dr Deanna DE BRUYN, Dr Hank DJERDJEV, Dr Alex DONG, Dr Ying FANG, Dr Hongjuan FIRKIN, Dr Kate FISHER, Dr Dianne GABORIEAU, Dr Marianne GALLAGHER, Dr Sean GANEVA, Dr Desislava GRAY-WEALE, Dr Angus HALDER, Mr Greg HARRIS, Dr Hugh HAWKETT, Dr Brian HUDSON, Dr Toby ISSA, Dr Fatiah JAIN, Dr Nirmesh JOLLIFFE, Dr Kate LARSEN, Dr Allan LEVINA, Dr Aviva LUCAS, Dr Nigel MACQUART, Dr Rene MAHIDASHT, Dr Reza MANGE, Dr Siyabonga MARSHALL, Dr Craig McDONALD, Dr James McDONOUGH, Dr Matthew MORAN, Dr Damian MULCAHY, Dr Clodagh NAUTA, Dr Klaas NGUYEN, Dr Duc 153 154 PERRY, Dr Alexis PETERSON, Dr Vanessa PETHERICK, Dr Janice PETRAVIC, Dr Janka PHAM, Dr T T Binh RADOM, Prof Leo REIMERS, Prof Jeff REYNOLDS, Dr Aaron RICH, Dr Anne SACCAVINI, Dr Catherine SINTIC, Dr Paul SOUTHON, Dr Peter SPRONG, Dr Ewan STAMFORD, Dr Patrick TAYLOR, Dr Mark THOMPSON, Dr Keiran THORDARSON, Dr Pall VAN DE WATER, Dr Leon WANG, Dr Yanjun WANG, Dr Yun WARD, Dr Antony WHITBY, Dr Catherine ZHOU, Dr Qingdi ZHOU, Dr XIANGTING ZONDANOS, Ms Hollie Honorary Staff ARMSTRONG, A/Prof Bob ARONEY, Dr Manuel BACSKAY, Dr George BARNES, Dr Craig CHIA, Dr Peter ECKERT, Dr Jim FAILES, Dr Tim FIELDER, Dr Simon FREEMAN, Prof Hans GUO, Mr Chris HALL, Mr Matt HIDI, Mr Peter HUNTER, A/Prof Bob HUSH, Prof Noel JAMES, Dr Julia MACKIE, A/Prof John PINHEY, Prof John RADFORD, Dr Don SANGSTER, Mr David STERNHELL, Prof Sev TAYLOR, Prof Wal WEDER, Dr Jane WEI, Dr Gang WILLIAMS, Dr Alan School of Chemistry Annual Research Report Administrative & Finance Staff HURST, Dr Jeanette LAZER, Dr Warren MATTERSON, Ms Pat MOERMAN, Ms Rachel PATSALIDES, Ms Sophie PENWRIGHT, Mr Philip PERERA, Mrs Shanthi SANTOSA, Ms Trisanti SUTJIADI, Ms Stella THOMPSON, Ms Gemma WOODS, Ms Anne WOODS, Ms Kate WU, Ms Lisa Technical & Professional Staff ARMSTRONG, Mr Jeff BARASOAIN, Mr Fernando CARTER, Dr Elizabeth CHEE, Dr Clinton DELLIT, Mr Bruce DUCKWORTH, Mr John FISHER, Dr Keith GARSKE, Mr Arthur GATFIELD, Mr Cliff GOPAL, Mr Hitendra IONN, Mr Howard JENSEN, Dr Paul KAEGI, Mr Marcel KENT, Mr John LA, Mr Tuan LOGGE, Mr Bernie LUCK , Dr Ian OPRYSA, Mrs Anna PICKER, Dr Kelvin PISCICELLI, Mr Carlo POPIOLKIEWICZ, Mr Jarek SAINSBURY, Mr James TURNER, Dr Peter TURNER, Mr Mike WHANG, Mr Barry 155 156 School of Chemistry Research Assistants ALI, Mr Mohamed TEO, Ms Chih-Lynne Honours Students AIVAZIAN, Ms Karina BAIN, Mr James BARISIC, Ms Ivanka CHING, Mr Vincent CLEMENTS, Mr Richard COCHRANE, Mr James DOAN, Mr John DONA, Mr Anthony DUYKER, Mr Samuel EJJE, Ms Najwa FOIS, Mr Alessandro GWEE, Ms Yee Yen HAMBLY, Mr Adam HERNANDEZ AMEZQUITA, Mr Javier IOPPOLO, Mr Joseph KAN, Ms Casina KHAN, Mr Arfhan KOKIBAC, Mr Simon-Peter* KONKOLEWICZ, Mr Dominik LAU, Mr Vincent LEUNG, Ms Wing Yan LOKE, Mr Ping MCKENZIE, Mr Scott MERRICK, Mr Jeffrey MORRIS, Mr Christopher MOUSSA, Ms Iman Ahmed NGUYEN, Mr Truclam NGUYEN, Ms Annie PEATE, Mr Jonathan PHILLIPS Mr Anthony PIGOTT, Mr Adam STEWART Ms Rhinnon TING, Mr Jimmy TONG, Ms Katie TROY, Mr Tyler Patrick WILKINSON, Mr Shane WONG, Ms Shwomun YAMAMOTO, Ms Natsuho YOUNG, Mr Philip ZHANG, Ms Jenny * Mr Simon-Peter Kokibac tragically died on the 25 April, 2006. A memorial plaque has been erected in the Chemistry Courtyard in remembrance of Simon-Peter. Annual Research Report Postgraduate Students AMOORE, Mr Jarred AQUINO, Ms Cindy ARAOS, Mr Miguel AUNGSUPRAVATE Ms Ornsiri BANISTER, Mr Sam BEARE, Ms Kaitlin BEVITT, Mr Joseph BLOM, Ms Annabelle BONNITCHA, Mr Paul BRAY, Mr David BROOKER, Mr Lance BROTHERHOOD, Mr Peter BUTLER, Mr Stephen CAFE, Mr Peter CANFIELD, Mr Peter CARTER, Ms Melody CAWLEY, Mr Adam CERGOL, Ms Katie CHANG, Mr Jung Chi CHAPMAN, Ms Karena CHATJAROENPORN, Ms Khwanrat CHIN, Mr Yiing CLEGG, Mr Jack CROSSLEY, Ms Ellen CUEVAS, Ms Rosa EDWARDS-DAVIS, Mr David FISCHER, Mr Josh GIBSON, Mr Bligh GONG, Ms Xiao Juan GREEN, Mr Malcolm GUEST, Ms Ruth GUNOSEWOYO, Mr Hendra HALLIDAY, Ms Jill HAQUE, Mr Enamul HOSSEINI NEJAS, Ms Elham HUGHES, Mr Peter IREMONGER, Mr Simon IVANIC, Miss Sandra KAUR, Mrs Ravinder KAY, Ms Danielle KAZA, Mrs Arati KHOURY, Mr Tony KOKKIN, Mr Damian LESIC, Ms Rebecca LESWIN, Mr Joost McALPINE, Ms Jeannette MENON, Mrs Ambili MILLER, Mr Daniel MITCHELL, Mr Christopher MULYANI, Ms Irma NEW, Ms Elizabeth OBANDO GUTIERREZ, Mr Daniel 157 158 O’CONNOR, Mr Sean PAKCHUNG, Ms Amalie PETERSON, Mr Josh PRASAD, Mr Shiva PU, Mr Fan READ, Mr Justin RICHMOND, Mr Craig REILLY, Mr Neil ROBERTON, Mr Mark ROWLING, Mr Steven SAINES, Mr Paul SALOUROS, Ms Helen SAYYADI, Mr Nima SCHILTER, Mr David SCHULTZ, Ms Tennille SCHUSTER-WOODHOUSE, Ms Allira SCIORTINO, Ms Natasha SEABROOK, Mr Shane SENGUPTA, Mr Devashish SHARMA, Mr Neeraj SHARMA, Mrs Vikashni Vandana SHASHA, Ms Adelle SIMPKINS, Ms Grace SIMPSON, Ms Pip SINTIC, Ms Maxine SOLOMON, Ms Gemma STADTMUELLER, Ms Lisa STOCKS, Mr Danial SYNA, Mr Ritnesh SZCZEPINA, Mr Cody TAM, Mr Koman TAYLOR, Mr James THICKETT, Mr Stuart THOROGOOD, Mr Gordan J TOPP, Ms Kathryn TRONOFF, Mr Ashley WARD, Ms Rachelle M WEBB, Mr James WHAN, Ms Renee WIDMER-COOPER, Mr Asaph WILLOUGHBY, Mr Douglas WOOD, Mr Geoffrey WYCZESANY, Mr Tomasz YAP, Mr Benjamin YEUNG, Ms Alexandra YOUSSEF, Mr Ali ZHANG, Mr Hui ZIOLKOWSKI, Ms Erin School of Chemistry Annual Research Report Visitors BARTHOLOMäUS, Mr Ruben CHAN, Dr Bun CONSTABLE, Professor Ed EL-FAYYOUMY, Ms Shaimaa GHEIBI, Mr Nematollah GRAHAM, Dr David MEEJOO, Dr Siwaporn MULLINS, Dr Joe ORVIG, Professor Chris SANDALA, Mr Greg SEURING, Mr Jan 159 160 School of Chemistry 2006 Chemistry Graduates 162 School of Chemistry Annual Research Report Graduates of 2006 Mr Joseph Anthony Ioppolo Boronated Phosphonium Salts as a New Class of Agents for Boron Neutron Capture Therapy Supervisor: Dr Louis Rendina Bachelor of Science (Honours) Ms Casina Wing Sze Kan Metabolism of Chemopreventative Selenium Nutritional Supplements In Vitro Supervisor: Dr Hugh Harris The following students had their degrees awarded in 2006:Ms Karina Aivazian Oxygen Non-Stoichiometry and Cation-Doping in Thermoelectric Misfit-Layered Cobaltates Supervisor: Dr Christopher Ling Mr James Hay Bain Investigating Mutant ß-glycosidases: Synthesis and Analysis of Drug Metabolites Supervisor: Dr Malcolm McLeod Ms Ivanka Terezia Barisic Defect Perovskites and Lithium Intercalation Supervisor: Dr Siegbert Schmid Mr Hong Yue Vincent Ching Novel DNA Metallointercalators for Boron Neutron Capture Therapy Supervisor: Dr Louis Rendina Mr Richard James Clements Semi-Empirical Nucleation Theory in Binary Eutectic Alloys Supervisor: Professor Peter Harrowell Mr James Robert Cochrane Towards the Synthesis of an Antifungal Cyclic Peptide Supervisor: Dr Katrina Jolliffe Mr John Nguyen Phuc Doan Modified MMP Inhibitors as Potential Radiodiagnostic Agents for Metastatic Cancer Supervisors: Professor Trevor Hambley and Associate Professor Michael Kassiou Mr Anthony Dona Relating Diffusion and Dissolution Properties of Starch with its Digestability Supervisor: Professor Robert Gilbert Mr Samuel Duyker Lanthanoid Hexacyanometalates: Negative Thermal Expansion and Hydration Characteristics Supervisor: Professor Cameron Kepert Ms Najwa Ejje A Novel Application of Immobilized Metal Affinity Chromatography (IMAC) for Siderophore Purification Supervisor: Dr Rachel Codd Ms Yee Yen Gwee Investigations of the Anti-Metastatic Properties of NAMI-A and its Biotransformations in Blood Supervisor: Professor Peter Lay Mr Adam Christopher Hambly Porphyrin-Appended Dendrimers: Synthesis, Structure and Function Supervisor: Professor Maxwell Crossley Mr Arfhan Khan The Synthesis and Magnetism of Transition Metal Borates Supervisor: Dr Christopher Ling Mr Dominik Lech Konkolewicz A Model for Starch and Other Hyperbranched Polymers Supervisors: Dr Angus Gray-Weale and Professor Robert Gilbert Mr Vincent Wing-Hei Lau Towards Hydrogen Generation by the Photocatalytic Splitting of Water Supervisors: Professor Thomas Maschmeyer and Associate Professor Anthony Masters Ms Wing Yan Leung Asymmetric Catalytic Synthesis of Praziquantel Supervisor: Dr Matthew Todd Mr Ping Loke Synthesis of the C17-C25 Fragment of (-)-Lasonolide A Supervisor: Dr Mark Coster Mr Scott Dylan McKenzie Aurivillius Phases as a Framework for Multiferroic Materials Supervisors: Dr Christopher Ling and Associate Professor Brendan Kennedy Mr Jeffrey Merrick An Evaluation of Harmonic Vibrational Frequency Scale Factors Supervisors: Professor Leo Radom and Dr Damian Moran Mr Christopher William Morris Extraterrestrial Metastable Species: Towards a Better Understanding of the Interstellar Environment Supervisor: Dr Timothy Schmidt Ms Iman Ahmed Moussa Novel Sigam Selective Ligands: Synthesis and Resolution of Trishomocubanes Supervisors: Associate Professor Michael Kassiou and Dr Mark Coster Ms Annie Nguyen Speciation of Chromium and Vanadium Dietary Supplements In Vitro Supervisor: Professor Peter Lay Mr Truclam Nguyen TACA as a Biological Template for the GABAc Receptor Supervisor: Dr Meredith Jordan Mr Jonathan Andrew Peate Towards a Better Characterisation of Starch Supervisor: Professor Robert Gilbert 163 164 Mr Anthony Edward Phillips Tunable Thermal Expansion in Cyanide-Bridged Frameworks with Single-Network Diamond Topology Supervisor: Professor Cameron Kepert Mr Adam James Pigott Synthetic Studies Towards the F-Ring/Side-Chain of Spongistatin 1 Supervisor: Dr Mark Coster Ms Rhiannon Troye Stewart Microsclerodermin C: Methodologies Towards the Hydroxypyrrolidinone Fragment Supervisor: Dr Mal McLeod Mr Thirugnanasambanthar Thirukkumaran Asymmetric Synthesis with Dihydroisoquinolines Supervisor: Dr Matthew Todd Mr Sai Chung Jimmy Ting A Structural Study of B-Cation Substituted Lanthanum Rhodates Supervisor: Associate Professor Brendan Kennedy Ms Katie Wing Ki Tong Self-Assembled Gels From Small Organic Molecules Supervisor: Dr Pall Thordarson Ms Shwo Mun Wong New Iron-Based Reagents for the Dihydroxylation of Alkenes Supervisor: Dr Peter Rutledge Ms Natsuho Yamamoto Fluorescent Hydroxamic Acids as Models of Cytotoxins in Hypoxia-Selective Cobalt Prodrugs Supervisor: Professor Trevor Hambley Mr Philip Young Cyclic Peptide Molecular Scaffolds: Synthesis and Anion Binding Supervisor: Dr Katrina Jolliffe Ms Jenny Zhang Lysosomal Localisation of Platinum(II)-Anthraquinone Complexes Supervisor: Professor Trevor Hambley Mr Christopher James Charles Watts Interpreting Size-Exclusion Data for Hyper-Branched Polymers: A glimpse at Starch Supervisors: Dr Angus Gray-Weale and Professor Robert Gilbert Mr Shane Michael Wilkinson Glucuronylsynthase: A Novel “Designer Enzyme” to Catalyse Glucuronylation Supervisor: Dr Malcolm McLeod School of Chemistry Annual Research Report Master of Science The following students had their degrees awarded in 2006:Mr Ahmad Faiz Abdul Latip Nanoporous Lanthanoid–Oxalate Framework Materials: Characterisation and Host-Guest Properties Supervisor: Professor Cameron Kepert Associate Supervisor: Associate Professor Brendan Kennedy Mr Mark Absalom Porphyrin-Appended and Dendrimers for Use in Photonics and Catalysis Supervisor: Professor Maxwell Crossley Associate Supervisor: Dr Robert Baker Doctor of Philosophy The following students had their degrees awarded in 2006:Dr Rebecca Alderden The Distribution of Platinum Complexes in Biological Systems Supervisor: Professor Trevor Hambley Associate Supervisor: Professor Margaret Harding Dr Joseph Bevitt Functionalised Nanoporous Molecular Materials Supervisor: Professor Cameron Kepert Associate Supervisor: Professor Jeffrey Reimers Dr Malcolm Green Characterisation, Modification and Loading of Nanotubular Clays for Controlled Release Technologies Supervisor: Professor Cameron Kepert Associate Supervisor: Dr Hui Zhu Dr Tony Khoury Multiple Connector Building Blocks for Use in Novel Porphyrin Assemblies Supervisor: Professor Maxwell Crossley Associate Supervisor: Professor Jeffrey Reimers Dr Nicholas Lambropoulos Design of a Directed Self-Assembled Molecular N-Bit Shift-Register Memory Device Supervisor: Professor Jeffrey Reimers Associate Supervisors: Dr George Bacskay and Professor Maxwell Crossley Dr Ignace Louis The Total Synthesis of the Cytotoxic Marine Macrolide (-)-Dactylolide Supervisor: Dr Malcolm McLeod Associate Supervisor: Dr Craig Hutton 165 166 School of Chemistry Dr Emily Shuter Studies Toward the Synthesis of the Microsclerodermin Natural Products Supervisor: Dr Malcolm McLeod Associate Supervisor: Dr Mark Coster Dr Appadurai Thiyakesan Nanoporous Molecular Framework Materials of Mixed-Donor Ligands with Lanthanoids and Transition Metals Supervisor: Professor Cameron Kepert Associate Supervisor: Emeritus Professor Leonard Lindoy 167 Annual Research Report Honours & Postgraduates 2006 Below are some of our Chemistry Honours and Postgraduate students. Honours Students Dr Jenny Waern The Biological Chemistry of the Antitumor Agent Molybdocene Dichloride Supervisor: Professor Margaret Harding Dr Asaph Nathan Widmer-Cooper Structure and Dynamics in Two-Dimensional Glass-Forming Alloys Supervisor: Professor Peter Harrowell Associate Supervisor: Dr George Bacskay Dr Geoffrey Wood Radical-Mediated Protein Oxidation Supervisor: Professor Leo Radom Associate Supervisor: Dr George Bacskay Dr Alexander Yuen Synthetic Studies Towards Stephanotic Acid Supervisor: Dr Katrina Jolliffe Associate Supervisor: Dr Craig Hutton Postgraduate Students 168 School of Chemistry