RESEARCH HIGHLIGHTS 1995 - Present

Biological Chemistry

Inorganic Chemistry

Organic Chemistry

Physical and Theoretical Chemistry

Visiting Fellows (Post Retirement)

 

BIOLOGICAL CHEMISTRY

DIXON, Dr N. - Protein Synthesis and Evolution

Proofreading during DNA synthesis. The enzymes that copy DNA in cells that are about to divide, called DNA polymerases, sometimes make mistakes. If these are not corrected, they lead to mutations that cause disease. The frontline defence against copying errors is another enzyme called a proofreader. We have determined the highest-resolution structure yet available for a replicative proofreader bound to a product of the reaction it promotes. This has enabled us to study the way it works in great detail, and contributes to an intense worldwide effort to understand how DNA polymerases work.^[1]

[1] Hamdan, S., Carr, P.D., Brown, S.E., Ollis, D.L., Dixon, N.E. Structural basis for proofreading during replication of the Escherichia coli chromosome. Structure, 10, 535-546 (2002).

KENIRY, Dr M. A. - Nuclear Magnetic Resonance

Guanine-rich segments of nucleic acids are found in biologically significant regions of the genome in particular at the promotor sites of highly proliferating cells. These segments frequently form four-stranded structures called quadruplexes. Keniry has contributed significantly to our understanding of quadruplex structure and stability by his discovery of the first quadruplex with sequential guanines in the syn conformation and the subsequent completion of a high-resolution NMR structure of this quadruplex.^[1] The solution structure has led to an understanding of the unusual stability of the folded form of this quadruplex.^[2] Later work hasfocussed on binding of small molecules to DNA quadruplexes and, in particular, the unexpected finding that spermine has a stronger affinity for folded DNA quadruplexes over duplex DNA and linear quadruplexes. This work was only possible using a novel NMR approach and specific labelling of spermine.

[1] Keniry, M.A., Strahan, G., Owen, E.A., Shafer, R.H., The solution structure of the Na⁺ form of the dimeric G-quadruplex, [d(G₃T₄G₃)]₂. Eur. J. Biochem. 233, 631-643 (1995).

[2] Keniry, M. A. Quadruplex structures in nucleic acids. Biopolymers 56, 123-146 (2001).

OLLIS, Dr D. - Protein Crystallography and Engineering

Ollis seeks to provide a chemical basis for understanding complex biological molecules. He is engaged in research with signal transduction molecules and a number of enzymes. The signal transduction molecules include molecules on the surface of eukaryotic cells along with molecules found in the cytoplasm of bacteria. The cell surface molecules include the b common Il5 receptor whose structure was determined in collaboration with Professor Ian Young of the John Curtin School of Medical Research. This work is described in the paper published in Cell.^[1] The bacterial protein, PII, is involved in the regulation of nitrogen flow in bacteria. Ollis was responsible for the first structure; this and subsequent structures give an explanation for how this protein modulates the activities of numerous enzymes throughout the cell.^[2]

Of the enzymes being studied in the Ollis group, a number have been the subject of directed evolution and structural studies. The work with an organophosphates degrading enzyme (OPDA), published in Protein Engineering is an example of this approach. The paper describing the isolation of a gene for a glycerophosphodiesterase was the result of work aimed at finding an enzyme that could degrade the product of the OPDA enzyme and allow E. coli to use the phosphate in phosphate pesticides as the sole source of phosphate; in essence to grow on pesticides.^[3]

[1] Carr, P.D., Gustin, S.E., Church, A.P., Murphy, J.M., Ford, S.C., Mann, D.A., Woltring, D.M., Walker, I., Ollis, D.L., Young, I.G. Structure of the complete extracellular domain of the common b subunit of the human GM-CSF, IL-3 and IL-5 receptors reveals a novel dimer configuration. Cell 104, 291-300 (2001).

[2] Xu, Y., Cheah, E., Carr, P.D., van Heeswijk, W.C., Westerhoff, H.V., Vasudevan S.G., Ollis D.L. GlnK, a P_II - homologue: structure reveals ATP binding site and indicates how the T-loops may be involved in molecular recognition. J. Mol. Biol. 282(1), 149-165 (1998).

[3] Yu-McLoughlin, S., Jackson, C., Liu, J.-W., Ollis, D.L. Growth of Escherichia coli coexpressing phosphotriesterase and glycerophosphodiesterase using paraoxon as sole phosphorus source. Appl. Environ. Microbiol. 70(1), 404-412 (2004).

OTTING, Professor G. - Biological NMR

Otting's research focus is on techniques in nuclear magnetic resonance (NMR) spectroscopy which are of direct interest for rapid protein analysis in the pharmaceutical industry. While all major pharmaceutical companies use two-dimensional ¹⁵N-¹H correlation spectra of ¹⁵N-labelled proteins to identify drug binding sites on protein surfaces, the assignment of these signals is usually costly and time-consuming. Very recently, however, Otting's group invented a much faster way of assignment. The requirements are (i) knowledge of the three-dimensional protein structure, obtained by X-ray crystallography, (ii) one or several selectively ¹⁵N-labelled protein samples, and (iii) a lanthanide binding site. The assignments result from two highly sensitive ¹⁵N-¹H correlation spectra recorded with and without paramagnetic lanthanide and comparison with predictions of the paramagnetic effects based on the crystal structure. No costly ¹³C and ²H labelling or time-consuming three-dimensional NMR spectroscopy is required.^[1]

[1] Pintacuda, G., Keniry, M.A., Huber, T., Park, A.Y., Dixon, N.E., Otting, G. Fast structure-based assignment of ¹⁵N-HSQC spectra of selectively ¹⁵N-labeled paramagnetic proteins. J. Am. Chem. Soc. 126, 2963-2970 (2004).

OAKLEY, Dr A. J. - Structural Biology

Oakley has made several contributions in the field of structural biology. The most recent outstanding contribution has been to the understanding of an enzyme called LinB, which hydrolyses haloalkanes to their corresponding alcohols. Oakley was able to determine the three-dimensional structure of this enzyme at 0.95 Angstrom resolution using synchrotron radiation. Only 12 enzymes (out of over 11,000 enzyme structures in the Protein Data Bank) of similar or larger size have been determined at this or better resolution. This has allowed the direct observation of the dynamic disorder of the active site residues to be observed, and together with ab-inito QM calculations, has provided unique insights into the activity of this enzyme.^[1]

[1] Oakley A.J., Klvana M., Otyepka M., Nagata Y., Wilce M.C.J., Damborsky J. Crystal structure of haloalkane dehalogenase LinB from Sphingomonas paucimobilis UT26 at 0.95 Å resolution: dynamics of catalytic residues. Biochemistry 43(4), 870-878, (2004).

 

INORGANIC CHEMISTRY

HEATH, Dr G. A. - Coordination Chemistry and Spectro-electro Chemistry

The Heath group has an international reputation for their conceptual approach to the investigation of molecular and electronic structure, combining electrochemical and spectroscopic methods for the study of redox-active compounds. Most notably, in collaboration with Dr Richard Bramley, they demonstrated how to overcome the formidable difficulties of combining immensely valuable Nuclear Magnetic Resonance (NMR) spectroscopy with simultaneous voltage-controlled electrolysis, and in 2000 the team published an authoritative account of the world's first practicable electrogenerative cell for true in-situ high-field NMR detection.^[1]

[1] Prenzler, P.D., Bramley, R., Downing, S.R., Heath, G.A. High-field NMR spectroelectrochemistry of spinning solutions: simultaneous in situ detection of electrogenerated species in a standard probe under potentiostatic control. Electrochem. Commun. 2(7), 516-521 (2000).

HILL, Professor A. F. - Synthetic Organometallic and Coordination Chemistry

Hill has for a number of years made significant contributions to the field of metal-carbon multiplebond synthesis (alkylidenes, alkylidynes, allenylidenes, chalco-carbonyls etc). Recently, this has resulted in the first general route to bimetallics bridged by linear tricarbido C₃ ligands^[1] offering the possibility of electronic communication between metals and also serving as building blocks for more elaborate cluster ensembles. Although it had long been proposed, Hill'sgroup has been able to confirm for the first time the existence of metal-boron dative bonding in a group of remarkable cage structures - so called metallabortranes.

[1] Dewhurst, R.D., Hill, A.F., Smith, M.K. Heterobimetallic C₃ complexes through silylpropargylidyne desilylation. Angew. Chem., Int. Ed. 43, 476-478 (2004).

WILD, Professor S. B. - Inorganic Stereochemistry and Asymmetric Synthesis

Wild's splendid work on the synthesis and resolution of chiral phosphines and arsines continues with the recent isolation and structural characterisation of the three, enantiomerically pure, diastereomers of a linear hexa(tertiary phosphine) containing four resolved, chiral phosphorus centres^[1] The strongly helicating form of the hexaphosphine combined with copper(I) to generate, by stereoselective self-assembly, a complex in which two of the hexaphosphine-ligand strands were wound around three metal ions in a parallel, protein-like, double a-helix arrangement.

[1] Bowyer, P.K., Cook, V.C., Gharib-Naseri, N., Gugger, P.A., Rae, A.D., Swiegers, G.F., Willis, A.C., Zank, J., Wild, S.B. Configurationally homogeneous diastereomers of a linear hexa(tertiary phosphine): enantioselective self-assembly of a double-stranded parallel helicate of the type (P)-[Cu₃(hexaphos)₂](PF₆)₃. Proc. Natl. Acad. Sci. (USA) 99, 4877-4882 (2002). (Invited Paper - Special issue on Supramolecular Chemistry and Self-Assembly edited by J. Halpern).

WITHERS, Professor R. L. - Solid State Inorganic Chemistry (with Prof. A. D. Rae)

The research of the Withers' group focusses on the factors that determine the balance between local crystal chemistry and long range order in a wide range of compositionally and/or displacively flexible crystalline systems: wide range non-stoichiometric solid solutions, displacively flexible framework structures, ferroic phases and incommensurately modulated structures. Recent achievements include the use of composite modulated structure formalism to describe, refine and interpret a range of "infinitely adaptive" solid solutions^[1] and the discovery and subsequent modelling of inherent displacive flexibility and its consequences in a range of flexible framework structures (see, for example, Reference [2]).

[1] Withers, R.L., Schmid, S., Thompson, J.G. Compositionally and/or displacively flexible systems and their underlying crystal chemistry. Prog. Solid State Chem. 26, 1-96 (1998).

[2] Withers, R.L., Tabira, Y., Liu, Y., Höche, T. A TEM and RUM study of the inherent displacive flexibility of the fresnoite framework structure type. Phys. Chem. Miner. 29, 624-632 (2002).

RAE, Professor A. D. - Solid State Inorganic Chemistry (with Prof. A. D. Withers)

Rae has a major research interest in the evaluation and refinement of problem crystal structures and has for many years used and developed his own program system RAELS to allow problem identification and comprehensive constrained least squares refinement procedures to obtain important structure determinations. The use of refinable local coordinates with respect to refinable local orthonormal axis systems allows the simple application of equal object constraints and local symmetry restraints. The use of refinable rigid body atomic displacement models define relative to principal axes of libration allows controllable constraints that reduce the number of variables while maintaining essentially full anisotropic refinement. A wide variety of restraints can also be used and restraints on bond valence have been successfully used in the powder refinement of the commensurately modulated structure CeTaO_4.17.^[1] A modulated structure approach has been shown to be very useful for many problems^[1-5] allowing the identification of an idealised parent structure or parent substructures^[2] of higher symmetry. This helps understand the true nature of a problem as the lost symmetry can be associated with twinning, disorder and stacking faults. The use of symmetrised components of the structure each associated with its own component of the diffraction data allows sensible comparative refinement to distinguish between competing structure models by determining which reflections are sensitive to model differences. Structures that have retained a special interest to Rae are ones that may be described as basis functions for a doubly degenerate irreducible representation of a 1:1 disordered parent structure.^[3,5] Twinning and stacking faults are essentially unavoidable in such structures and polytypes are possible.^[5]

[1] Thompson, J.G., Rae, A.D., Bliznyuk, N., Withers, R.L. Chemically restrained refinement of CeTaO_4+x (x ≅ 0.17) superstructure. J. Solid State Chem. 144, 240-246 (1999).

[2] Haller, K.J., Rae, A.D., Heerdegen, A.P., Hockless, D.C.R., Welberry, T.R. The four fold disordered structures of p-chloro-N-(p-methylbenzylidine)aniline and p-chloro-N-(p-methylbenzylidine)aniline. Acta Cryst. B51, 187-197 (1995).

[3] Rae, A.D., Schmid, S., Thompson, J.G., Withers, R.L., Ishizawa, N. The crystal structures of Ta₂₂W₄O₆₇ and Ta₇₄W₆O₂₀₃. II. A composite modulated structure approach to the (1-x)Ta₂O₅.xWO₃, 0 ≤ x ≤ 0.267, solid solution. Acta Cryst. B51, 709-721 (1995).

[4] Rae, A.D., Craig, D.C., Dance, I.G., Scudder, M.L., Dean, P.A.W., Kmetic, M.A., Payne, N.C., Vittal, J.J. The pseudosymmetric structure of Pb(SPh)₂. Acta Cryst. B53, 457-465 (1997).

[5] Rae, A.D., Willis, A.C. 9,10 Phenanthrenequinone, not your average structure. Z. Krist. 218, 221-230 (2003).

WEBSTER, Dr R. D. - Electrochemistry

Webster’s research is directed at experimental electrochemistry, aimed at gaining new information regarding complex chemical reaction mechanisms involving electron transfer, and developing methods for stabilizing species in unusual oxidation states. Significant successes include procedures for preparing the highly reactive C₆₀^+· radical^[1] and calculating the kinetics of dimerization of radical anions.^[2] These studies have frequently involved overcoming the difficulties of combining electrochemistry with spectroscopy and resulted in the development of novel spectroelectrochemical cells, including in situ electrochemical cells for EPR spectroscopy, IR spectroscopy,^[3] UV-VIS-NIR spectroscopy and ellipsometry. The most recent focus of Webster’s research is aimed at overcoming the experimental difficulties associated with combining electrochemistry with one of the most widely used and powerful spectroscopic techniques, NMR spectroscopy.^[4]

[1] Webster, R.D., Heath, G.A. Voltammetric, EPR and UV-VIS-NIR spectroscopic studies associated with the one-electron oxidation of C₆₀ and C₇₀ in 1,1',2,2'-tetrachloroethane containing trifluoromethanesulfonic acid. Phys. Chem. Chem. Phys. 3(13), 2588-2594 (2001).

[2] Webster, R.D. EPR and voltammetric evidence for the reversible dimerization of anion radicals of aromatic meta-substituted diesters and dithioic S,S’-diesters. J. Chem. Soc., Perkin Trans. 2 (2), 263-269 (1999).

[3] Webster, R.D. In situ electrochemical-ATR-FTIR spectroscopic studies on solution phase carboxylate radical anions. J. Chem. Soc., Perkin Trans. 2 (11), 1882-1888 (2002).

[4] Webster R.D. In situ electrochemical-NMR spectroscopy. Reduction of aromatic halides. Anal. Chem. 76(6), 1603-1610 (2004).

 

ORGANIC CHEMISTRY

BANWELL, Professor M. G. - Synthesis and Mechanism

Both terrestrial and marine organisms found in Australia have proven to be a rich source of structurally remarkable and biologically potent compounds. However, for environmental reasons, such sources cannot be continuously "plundered" to secure the large quantities of material required for comprehensive biological evaluation. As such it is up to chemists to redress matters through the development of total syntheses of relevant targets. The Banwell group has been remarkably successful in this regard having achieved, for example, a total synthesis of lamellarin K,^[1] a complex marine alkaloid derived from a rare sponge found on the Great Barrier Reef and now being developed for the treatment of lung cancer. Indeed, the synthesis is so efficient that enough material has been prepared to support, through a licensing agreement with the pharmaceutical development company, PharmaMar, all the phase 1 clinical trials. In a related vein, the eighteen-membered and highly oxygenated macrolide aspicillin,^[2] which is obtained from certain types of lichen found in South Eastern Australia, has also been prepared by the Banwell group through a novel combination of enzymatic and metal-catalysed processes. Once again, the route developed is so efficient that multigram quantities of this material are now available for the first time. As such, comprehensive biological evaluation of aspicillin can now be undertaken. These studies are leading to the identification of substances capable of regulating certain important cellular processes.

[1] Banwell, M., Flynn, B., Hockless, D. Convergent total synthesis of lamellarin-K. Chem. Commun. 2259-2260 (1997).

[2] Banwell, M.G. and McRae, K.J. Chemoenzymatic synthesis of (+)-aspicilin from chlorobenzene. Org. Lett. 2, 3583-3586 (2000).

EASTON, Professor C. J. - Biochemical Reactions and Molecular Recognition

Following on from his earlier research on the use of host-guest complexes for the administration of pharmaceuticals, which resulted in drug formulations that are now in everyday, world-wide clinical use, Easton has pursued his interests in supramolecular chemistry to develop molecular reactors,^[1,2] and other miniature mechanical devices,^[3] The molecular reactors efficiently control the assembly of reactants to change the outcomes of chemical reactions, to give products that are otherwise not readily accessible. Easton has also continued to study free radical reactions of amino acids and peptides^[4,5] with the recent culmination of this work being the identification of radical resistant amino acids and the development of methods to regulate hormone production and treat associated disease states in humans and animals.

[1] Easton, C.J., Lincoln, S.F. Modified cyclodextrins. Scaffolds and templates for supramolecular chemistry. Imperial College Press: London, pp 1-293 (1999).

[2] Meyer, G., Easton, C.J., Lincoln, S.F., Simpson, G.W. b-Cyclodextrin as a scaffold for supramolecular chemistry, to reverse the regioselectivity of nitrile oxide cycloadditions. J. Org. Chem. 63 9069-9075 (1998).

[3] Onagi, H., Blake, C.J., Easton, C.J., Lincoln, S.F. Installation of a ratchet tooth and pawl to restrict rotation in a cyclodextrin rotaxane. Chem. Eur. J. 9, 5978-5988 (2003).

[4] Easton, C.J. Free radical reactions in the synthesis of α-amino acids and derivatives. Chem. Rev. 97, 53-82 (1997).

[5] Croft, K., Easton, C.J., Radom, L. Design of radical-resistant amino acid residues: a combined theoretical and experimental investigation. J. Am. Chem. Soc. 125, 4119-4124 (2003).

MANDER, Professor L. N. - Organic Synthesis

Mander has achieved wide international recognition for the development of strategies and methodology for the assembly of complex polycyclic natural products, as exemplified by his recent syntheses, e.g. of sordaricin [1] and the Galbulimima alkaloids that are endemic to North Queensland and Papua New Guinea [2]. In addition, Mander is recognized as the world authority on gibberellin research. His work in this field, as summarized in Reference [3] has been vital to research carried out by more than 50 groups worldwide on this important group of plant hormones. It has allowed the structures of some 60 new naturally occurring gibberellins to be determined and dramatically increased the range of gibberellins that can be accurately monitored by the provision of previously unavailable standards, thereby affording new insights into the biosynthesis, metabolism and transport of these compounds.

[1] Mander, L. N. Thomson, R. J., Total synthesis of Sordaricin. Org. Lett., 5,1321-1324 (2003).

[2] Mander, L.N., McLachlan, M.M. Total synthesis of the Galbulimima alkaloid GB 13. J. Am. Chem. Soc. 125, 2400-2401 (2003).
O'Connor, P. D., Mander, L. N., McLachlan, M. M. Synthesis of the Himandrine Skeleton. Org. Lett. 6, 703-706 [2004].

[3] Mander, L.N. Twenty years of gibberellin research. Nat. Prod. Rep. 20, 49-69 (2003).

SHERBURN, Dr M. S. - Organic Synthesis, Methodology and Host-Guest Chemistry

Sherburn has made significant contributions in total synthesis, efficient new methodology development, "fundamental" molecules and host-guest chemistry. Total synthesis: Podophyllotoxin, a natural product made by plants, is one of the most important substances in cancer chemotherapy. Since 1960, only seven plant-derived anticancer drugs have received FDA approval for commercial production in the USA: two are made from podophyllotoxin. The natural product was made in the RSC laboratories in 2003^[1] and since then, many new compounds related to podophyllotoxin have been made by the ANU group. New synthetic methodology: A very efficient and stereoselective route to tetracyclic compounds has been developed based upon sequences of intramolecular Diels-Alder reactions.^[2] Fundamental molecules: The first synthetic approach to the dendralene class of hydrocarbons has been developed.^[3] Host-guest chemistry. The preparation of some of the largest container molecules, capable of encapsulating guest molecules comprising over 100 atoms, has been achieved.^[4]

[1] Reynolds, J., Scott, A.J., Turner, C.I., Sherburn, M.S. The intramolecular carboxyarylation approach to podophyllotoxin. J. Am. Chem. Soc. 125, 12108-12109 (2003).

[2] Nörret, M., Sherburn, M.S. The zipper-mode domino IMDA reaction: a new 0®ABCD strategy for steroids and related compounds. Angew. Chem., Int. Ed. 40, 4074-4076 (2001).

[3] Fielder, S., Rowan, D.D., Sherburn, M.S. The first synthesis of the [n]dendralene family of fundamental hydrocarbons. Angew. Chem., Int. Ed. 39, 4331-4333 (2000).

[4] Barrett, E.S., Irwin, J.L., Edwards, A.J., Sherburn, M.S. Superbowl container molecules. J. Am. Chem. Soc. 126, 16747-16749 (2004).
 

 

PHYSICAL AND THEORETICAL CHEMISTRY

COLLINS, Professor M.A. - Theoretical Chemical Physics

The major research highlight of the Collins group since 1995 has been the development of a systematic and automated method to construct the molecular potential energy surfaces (PESs) which govern chemical reaction dynamics. These surfaces are essential to the theoretical simulations which complement and test experimental studies of fundamental chemical processes. The approach is a novel "first principles" method which interpolates ab initio quantum chemistry calculations of the electronic energy to produce a complete description of the energy for all relevant molecular geometries. The method is powerful because it is both systematic and efficient, as accurate as necessary, and does not rely on empirical input as did previous approaches.

Four of the five papers listed below highlight important stages in this advance. Reference [1] presented the first "proof of method". Reference [2] solved an important theoretical problem so that PESs could be constructed for reactions involving many atoms. The next paper^[3] presented an important improvement in accuracy, via a type of automated learning, so that PESs can be used reliably in quantum dynamics simulations of reactions. The impact of this advance is demonstrated by Reference [4] which reported the first completely "first principles" simulation of a chemical reaction for a polyatomic molecule. These four papers are rather technical, and a more readable introduction can be found in Theoretical Chemistry Accounts.^[5]

[1] Jordan, M.J.T., Thompson, K.C., Collins, M.A. Convergence of molecular potential energy surfaces by interpolation application to the OH + H₂ ® H₂O + H reaction. J. Chem. Phys. 102, 5647-5657 (1995).

[2] Thompson, K.C., Jordan, M.J.T., Collins, M.A. Polyatomic molecular potential energy surfaces by interpolation in local internal coordinates. J. Chem. Phys. 108, 8302-8316 (1998).

[3] Bettens, R.P.A., Collins, M.A. Learning to interpolate molecular potential energy surfaces with confidence: A Bayesian approach. J. Chem. Phys. 111, 816-826 (1999).

[4] Zhang, D.H., Collins, M.A., Lee, S.-Y. First-principles theory for the H + H₂O, D₂O reactions. Science 290, 961-963 (2000).

[5] Collins, M.A. Molecular potential-energy surfaces for chemical reaction dynamics. Theor. Chem. Acc. 108, 313-324 (2002).

COOTE, Dr M. L. - Computational Quantum Chemistry

Coote has made significant contributions to our understanding of the free-radical polymerisation process, one of the highlights of which was her demonstration via both experimental^[1] and theoretical approaches^[2] that penultimate unit effects are important in free-radical copolymerisation. Prior to this work, it had been widely assumed that these could be neglected, and hence almost all published reactivity parameters are based upon what now appears to be an incorrect model. Her work, which was recognised with the award of the 2001 IUPAC Prize for Young Scientists,^[3] has major implications for modelling and controlling this process, and is now being incorporated into the new generation of textbooks for this field. A feature of her research has been her introduction of computational quantum chemistry as tool for solving mechanistic problems in polymer chemistry, and she has played a leading role in developing the methodology for this purpose. The power of this computational approach to polymer chemistry has recently been highlighted by her work on the "RAFT" process for controlling free-radical polymerisation, where she was able to explain retardation^[4] and inhibition^[5] effects in certain RAFT systems. This work is providing a strong foundation for her current efforts to invent new methods for controlling this important industrial process.

[1] Coote, M.L., Davis, T.P. Copolymerization propagation kinetics of para-substituted styrenes: a critical test of the implicit penultimate model. Macromolecules 32, 3626-3636 (1999).

[2] Coote, M.L., Davis, T.P., Radom, L. Effect of the penultimate unit on radical stability and reactivity in free-radical polymerization. Macromolecules 32, 2935-2940 (1999).

[3] http://www.iupac.org/news/prize/2001/coote.html

[4] Coote, M.L., Radom, L. Ab initio evidence for slow fragmentation in RAFT polymerization. J. Am. Chem. Soc. 125, 1490-1491 (2003).

[5] Coote, M.L., Radom, L. Substituent effects in xanthate mediated polymerization of vinyl acetate: Ab initio evidence for an alternative fragmentation pathway. Macromolecules 37, 590-596 (2004).

EVANS, Professor D. J. - Liquid State Chemical Physics

The puzzle of how time-reversible microscopic equations of mechanics lead to the time-irreversible macroscopic equations of thermodynamics has been a paradox since the days of Boltzmann. Boltzmann simply side-stepped this enigma by stating "as soon as one looks at bodies of such small dimension that they contain only very few molecules, the validity of this theorem (the Second Law of Thermodynamics and its description of irreversibility) must cease." Today, we can state that the Fluctuation Theorem (FT) of Evans and colleagues^[1] is a generalised Second-Law like theorem that bridges the microscopic and macroscopic domains and links the time-reversible and irreversible descriptions. Unlike the Second Law, the FT is applicable to systems of all sizes, including small systems of current scientific interest, including nanomachines and molecular motors. In a recent experiment, the Sevick and Evans groups at ANU showed that energy from the surrounding fluid could be converted into work to "push" an optically trapped colloidal in apparent violation of the Second Law.^[2] The frequency of these experimentally-observed "violations" agrees quantitatively with the predictions of the Fluctuation Theorem. This work received considerable international attention in news services, press, magazines as well as in international science press, national radio programs, and popular science magazines.^[3]

[1] Evans, D.J., Searles, D.J. The Fluctuation Theorem. Adv. Phys. 51, 1529-1585 (2002).

[2] Wang, G.M., Sevick, E.M., Mittag, E., Searles, D.J., Evans, D.J. Experimental demonstration of violations of the Second Law of Thermodynamics for small systems and short time scales. Phys. Rev. Lett. 89(5), 050601/1-4 (2002).

[3] http://rsc.anu.edu.au/~evans/papers/selectnewsreportsFT.pdf

GILL, Professor P.M.W. - Theoretical Quantum Chemistry

Gill and his co-workers have recently made significant progress toward the development of a radical new approach to the biggest challenge in Quantum Chemistry, namely, the electron correlation problem. They have shown that a new function, the Wigner intracule, which describes the relative positions and momenta of electrons in a molecule, can be used to obtain accurate estimates of the electron correlation energy [1]. They have also performed the first ab initio self-consistent field calculations of the behaviour of ensembles of electrons confined within a box [2] and constructed a new density functional that is specifically designed for the calculation of molecular vibrational frequencies [3].

[1] P.M.W. Gill, D. Crittenden, D.P. O'Neill and N.A. Besley, Hartree-Fock-Wigner: A two-electron-density functional theory, Phys. Chem. Chem. Phys. (2005) in press

[2] S. Ghosh and P.M.W. Gill, Finite jellium models. I. Restricted Hartree-Fock calculations, Journal of Chemical Physics, 122 (2005) 154108/1-5

[3] C.Y. Lin, M.W. George and P.M.W. Gill, EDF2: A density functional for predicting molecular vibrational frequencies, Aust. J. Chem. 57 (2004) 365-370

KRAUSZ, Professor E. R. - Laser and Optical Spectroscopy

The reaction centre of Photosystem II is the most efficient photo-electric conversion system known. We have been able to compare low temperature spectra taken before and after light induced charge separation.^[1] This allowed us to identify those chromophores located close to the charges generated, via their electrochromic shifts. These measurements have not only helped map out the electronic structure of the reaction centre but have further led to revolutionary laser selective experiments that are leading us to a new and unexpected picture of this vitally important enzyme.

[1] Peterson Årsköld, S., Masters, V.M., Prince, B.J., Smith, P.J., Pace, R.J., Krausz, E. Optical spectra of synechocystis and spinach Photosystem II preparations at 1.7 K: identification of the D1-pheophytin energies and Stark shifts. J. Am. Chem. Soc. 125(43), 13063-13074 (2003).

RADOM, Professor L. - Computational Quantum Chemistry

Radom and his co-workers have used state-of-the-art ab initio molecular orbital calculations to model reactions mediated by vitamin B₁₂. Although these reactions have been extensively studied experimentally, there is certainly no consensus as to how they proceed. The calculations have provided new insights. They predict that protonation and/or deprotonation at appropriate sites facilitates the reactions, and that reactions that are facilitated by protonation (or deprotonation) are facilitated by the partial-proton-transfer that enzymatic hydrogen bonding can provide. For the particular reaction catalyzed by the enzyme methylmalonyl CoA mutase, it is predicted that a specific amino acid moiety within the enzyme (His244) is likely to play a major role in its effectiveness.^[1] If His244 is removed, the enzyme should be much less effective. Precisely such experiments have been subsequently carried out in the USA and the UK, and have confirmed the theoretical prediction. The reaction is slowed down by 2 to 3 orders of magnitude when His244 is "mutated out". This and other recent examples provide strong encouragement for the use of computer calculations in a predictive manner in the study of enzyme-catalyzed reactions.

[1] Smith, D.M., Golding, B.T., Radom, L. Understanding the mechanism of B₁₂-dependent methylmalonyl-CoA mutase: partial proton-transfer in action. J. Am. Chem. Soc. 121, 9388-9399 (1999).

SEVICK, Dr E. M. - Polymers and Soft Condensed Matter

Traditionally, polymer science has relied upon bulk measurements using techniques such as neutron/light scattering and rheology to characterise melts and solutions of polymers and biopolymers. These measurements provide useful information on an ensemble of molecules, but they are limited in that they do not detail individual molecules. Today, research at the forefront of chemistry and biology is at the single molecule level: examples include DNA for molecular storage and retrieval of biological information, as well as single protein molecules which act as chemo-mechanical motors. In the last decade, the advent of two new experimental techniques, Atomic Force Microscopy (AFM) and Optical Tweezers (OT), has advanced the study of single polymer chains and biopolymers. These techniques allow one to image and directly manipulate chains using picoNewton scale forces on length scales ranging from Ångstroms to microns. These experimental techniques have inspired new molecular-based theories and simulations, allowing combined experimental, simulation, and theoretical approaches to these single-chain problems. Some of the important advances in this area by the Polymers & Condensed Matter group of RSC include an accurate description of the complicated dynamics of an electrophoretically-driven molecular chain through an array of microlithographic posts;^[1] several theoretical and simulation descriptions of the "squashing" of compression of an end-tethered chain with the polished tip of an AFM probe (which can be done experimentally);^[2] the first AFM force measurement of the stretching of a single polymer chain in poor solvent which confirmed the Rayleigh-instability for unadsorbed, single polymer chains;^[3] and a theoretical description of why the same instability does not happen for chains adsorbed onto surfaces.^[4]

[1] Sevick, E.M., Williams, D.R.M. Collision of a field-driven polymer with a post: electrophoresis in microlithographic arrays. Phys. Rev. Lett. 76, 2595-2598 (1996).

[2] Guffond, M.C., Williams, D.R.M., Sevick, E.M. End-tethered polymer chains under AFM tips: compression and escape in theta solvents. Langmuir 13, 5691-5696 (1997).

[3] Sevick, E.M., Williams, D.R.M. Polymers grafted onto strongly adsorbing surfaces in poor solvents: stretching, fission, phase separation and globular micelles in 2D. Phys. Rev. Lett. 82, 2701-2704 (1999).

[4] Haupt, B.J., Senden, T.J., Sevick, E.M. Experimental evidence of the rayleigh instability in single polymer chains. Langmuir 18, 2174-2182 (2002).

WELBERRY, Professor T. R. - Disordered Materials

In 1998 Welberry et al.^[1] reported the development of a method for the analysis of diffuse X-ray scattering in which a Monte Carlo model is automatically fitted to observed data. This new methodology has the potential to make the analysis of diffuse scattering more routine, more quantitative and applicable to a wider variety of materials than hitherto possible. The work was also presented as the 'Lonsdale Lecture' given at the IUCr Congress in 1999. A later paper^[2] describes the use of the new methodology for a particular organic system, benzil. This represents the most quantitative study of diffuse scattering to date with levels of agreement approaching those obtained in conventional crystal structure determination using Bragg peak intensities. The analysis reveals a level of detail of the local structure not available from conventional crystal structure determination.

Trying to understand the defect structure of wüstite, Fe_1-xO, has occupied numerous workers over many years. The definitive 1997 paper^[3] describes how the complex diffraction pattern of wüstite arises and is influenced by the presence and distribution of different types of defects and the strain-fields that occur around them. Wüstite is one of a number of defect ceramic/oxide materials (others include cubic zirconia and mullite) that have been studied by the Welberry group and it has become increasingly apparent that strain plays a major rôle in dictating the nanoscale structure in all of them. The 2001 paper^[4] describes how the same basic strain mechanism can be used to explain the observed diffuse scattering in a wide range of different materials.

Although it is now almost 20 years since their first discovery in 1984 the structure of quasicrystals and their relationship to normal crystal phases continues to present great challenges for the structural scientist. Welberry is applying the methods developed for ordinary disordered crystals to try to understand the disorder phenomena that are present in these novel materials. The 2002 paper^[5] shows how the same kinds of strain effects that are observed in ordinary crystals are recognizable in quasicrystal diffraction patterns.

[1] Welberry T.R., Proffen, Th., Bown, M. Analysis of single-crystal diffuse X-ray scattering via automatic refinement of a Monte Carlo model. Acta Crystallogr. A54, 661-674, (1998).

[2] Welberry T.R., Goossens D.J., Edwards A.J., David, W.I.F. Diffuse X-ray scattering from benzil, C₁₄H₁₀O₂: analysis via automatic refinement of a Monte Carlo model. Acta Crystallogr. A57, 101-109 (2001).

[3] Welberry, T.R. and Christy, A.G. Defect distribution and the diffuse X-ray diffraction pattern of Wüstite, Fe_1-xO. Phys. Chem. Miner. 24, 24-38 (1997).

[4] Welberry, T.R. Diffuse X-ray scattering and strain effects in disordered crystals. Acta Crystallogr. A57, 244-255 (2001).

[5] Welberry, T.R., Honal, M. 'Size-effect'-like distortions in quasicrystalline structures. Z. Kristallogr. 217, 422-426 (2002).

WHITE, Professor J. W. - Solid State Molecular Science (with Dr P. A. Reynolds)

Industrial explosives, based on emulsions are a $2 billion p.a business for Orica (Australia)- the world's largest manufacturer. White's collaboration with them to use techniques of neutron contrast variation in small^[1] and ultra-small angle neutron scattering, and X-ray and neutron reflectivity,^[2] has allowed the structure of the emulsion-forming surfactant at the oil/water interface and elsewhere to be understood for the first time and there is significant new physical chemistry in this. Five papers have been published,^[1-5] but none further will be published until current patenting is completed. The work has attracted Company sponsorship with collateral ARC support, and the design and testing of new and more powerful surfactants has started. This strong industrial collaboration has also allowed White to initiate the joint industry-university UnIChe enrichment program for school and university students. Drs P. Reynolds, E. Gilbert, M. Henderson and J. Zank in the group deserve much credit for their contributions so far.

[1] Reynolds, P.A., Gilbert, E.P., White, J.W. High internal phase water-in-oil emulsions and related microemulsions studied by small angle neutron scattering. 2. The distribution of surfactant. J. Phys. Chem. B 105, 6925-6932 (2001).

[2] Reynolds, P.A., McGillivray, D., Gilbert, E.P., Holt, S.A., Henderson, M.J., White, J.W. Neutron and X-ray reflectivity from polyisobutylene-based surfactants at the air-water interface. Langmuir 19, 752-761 (2003).

[3] Reynolds, P.A., Gilbert, E.P. White, J.W. High internal phase water-in-oil emulsions studies by small angle neutron scattering. J. Phys. Chem. B 104, 7012-7022 (2000).

[4] Reynolds, P.A., Henderson, M.J., Holt, S.A., White, J.W. The interfacial structure of a high internal phase emulsion near a solid surface. Langmuir 18, 9153-9157 (2002).

[5] Reynolds, P.A., Henderson, M.J., White, J.W. A small angle neutron scattering study of the interface between solids and oil-continuous emulsions and oil based microemulsions. Colloids Surf., A 232, 55-65 (2004).

 

VISITING FELLOWS (POST-RETIREMENT)

BECKWITH, Professor A. L. J.

Since his retirement Beckwith has maintained his long standing interest in the structure, reactivity, biological significance and synthetic utility of organic free radicals. He has recently used theoretical and computational methods to identify the factors that underlie the very high efficiency and selectivity of novel methods for the preparation of alkaloids^[1] and new amino acid derivatives.^[2] He has also completed a very extensive and comprehensive survey (in press) of ESR data required for the further development of improved methods for determining radical structure and stability.^[3]

[1] Beckwith, A.L.J., Storey, J.M.D. Tandem radical translocation and homolytic substitution: a convenient and efficient route to oxindoles. J. Chem. Soc., Chem. Commun. 977-978 (1995).

[2] Axon, J.R., Beckwith, A.L.J. Diastereoselective radical addition to methyleneoxazolidinones: an enantioselective route to α-amino acids. J. Chem. Soc., Chem. Commun. 549-550 (1995).

[3] Brocks, J.J., Beckhaus, H.-D., Beckwith, A.L.J., Rüchardt, C. Estimation of bond dissociation energies and radical stabilization energies by ESR spectroscopy. J. Org. Chem. 63, 1935-1943 (1998).

BENNETT, Professor M. A.

Before his retirement, one of the main themes of Bennett's work in organometallic chemistry was the stabilization of the highly unsaturated, short-lived organic molecule benzyne on transition metal centres, particularly nickel, and the reactivity of the resulting complexes. Transition metal-mediated reactions of benzyne are attracting increasing interest as a means of synthesizing polynuclear aromatic compounds in a few steps from simple, readily available starting materials. Retbøll et al.^[1] describes a novel and potentially very simple procedure which has made available benzyne complexes not only of nickel, but, for the first time, palladium. The exploitation of this work must be left to others.

[1] Retbøll, M., Edwards, A.J., Rae, A.D., Willis, A.C., Bennett, M.A., Wenger, E. Preparation of benzyne complexes of Group 10 metals by intramolecular suzuki coupling of ortho-metalated phenylboronic esters: molecular structure of the first benzyne-palladium(0) complex. J. Am. Chem. Soc. 124, 8348-8360 (2002).

BRAMLEY, Dr R.

Bramley's research activity since retirement is both collaborative and consultative. The former is largely with Dr Wayne Hutchison at the Australian Defence Force Academy, and is concerned with some aspects of quantum computing. Consultative work is mainly undertaken with other areas within ANU, namely, Prof. Neil Manson's group at the Research School of Physical Sciences and Engineering, Dr Karin Ahrling in the Photobioenergetics group in the Research School of Biological Sciences, and Dr Ron Pace's group in the Department of Chemistry, Faculty of Science. Much of this work uses electron paramagnetic resonance spectroscopy. Some new types of EPR experiments are being developed.

BROWN, Dr D. J.

In his post-retirement years, Brown has sought to make use of his extensive original work and long experience in the area of nitrogenous heterocyclic chemistry by producing detailed books for the Wiley series "The Chemistry of Heterocyclic Compounds." Each such book has comprised a comprehensive and critical review of a single heterocyclic system: all known primary or secondary synthetic methods, physical and biological properties, reactions of all types of derivative, and a complete list of known compounds. Thus they aim to provide current bench-workers with an all-embracing summary for each system with indications of potentially rewarding aspects for further investigation. Of these eight books, the last four have appeared since 1996, covering original research during the previous 30 years or so in quinazolines, pyridazines, pyrazines, and quinoxalines respectively.^[1-4] A ninth such monograph on cinnolines and phthalazines is currently in preparation.

[1] Brown, D.J. The Quinazolines: Supplement I, Wiley: New York, pp xx + 736 (1996).

[2] Brown, D.J. The Pyridazines: Supplement I, Wiley: New York, pp. xviii + 687 (2000).

[3] Brown, D.J. The Pyrazines: Supplement I, Wiley: New York, pp. xvi + 557 (2002).

[4] Brown, D.J. Quinoxalines: Supplement II, Wiley: New York, pp. xvi + 510 (2004).

MACLEOD, Dr J. K.

The positional ¹³C isotopic analysis of labelled sugar phosphates described in Reference [1] allowed us to re-evaluate the Calvin pathway of photosynthesis using intact chloroplasts exposed to ¹³CO₂. This work is presently being written up for publication. Ramsay et al.^[2] describes a new, mild method for tagging sulfated oligosaccharides which finds particular application in the analysis of the structures of glycosaminoglycans such as heparins and heparan sulfates.

[1] MacLeod, J.K., Flanigan, I.L., Williams, J.F., Collins, J.G. Mass spectrometric studies of the path of carbon in photosynthesis: positional isotopic analysis of ¹³C-labelled C₄ to C₇ sugar phosphates. J. Mass Spectrom. 36, 500-508 (2001).

[2] Ramsay, S.L., Freeman, C., Grace, P.B., Redmond, J.W., MacLeod, J.K. Mild tagging procedures for the structural analysis of glycans. Carbohydr. Res. 333, 59-71 (2001).

RICKARDS, Professor R. W.

The publications provided exemplify the application of organic synthesis, biomimetic synthesis, and structural and stereochemical studies to compounds of medical and biological importance which characterised the research of the Biooganic Chemistry Group prior to Rickards' retirement in 1999. The tricyclic syringolides, specific signal molecules produced by a plant pathogenic Pseudomonas bacterium that trigger a hypersensitive defense response in resistant soybean cultivars, were obtained by biomimetic synthesis in four steps from D-xylulose, using a single protecting group.^[1] Conventional syntheses have required some twenty steps and multiple protecting groups. Biomimetic synthesis also supported the provocative proposed involvement of 6π electrocyclic ring closures in the biosynthesis of certain benzenoid natural products.^[2] Unique pentacyclic structures were defined for the calothrixins, cyanobacterial metabolites active at nanomolar concentrations against cancer cells and malaria parasites.^[3]

[1] Henschke, J.P., Rickards, R.W. Biomimetic synthesis of the microbial elicitor syringolide 2. Tetrahedron Lett. 37, 3557-3560 (1996).

[2] Rickards, R.W., Skropeta, D. Electrocyclic processes in aromatic biosynthesis: a biomimetic study of pseudorubrenoic acid A. Tetrahedron 58, 3793-3800 (2002).

[3] Rickards, R.W., Rothschild, J.M., Willis, A.C., de Chazal, N.M., Kirk, J., Kirk, K., Saliba, K.J., Smith, G.D. Calothrixins A and B, novel pentacyclic metabolites from Calothrix cyanobacteria with potent activity against malaria parasites and human cancer cells. Tetrahedron 55, 13513-13520 (1999).

SARGESON, Professor A. M.

The publications nominated display aspects of research which may be potentially valuable in the future. The cage chemistry in References [1] and [2] describe molecules some of which, may be useful in energy trapping and conversion, will retain some toxic metal ions, are useful reagents to destroy nematodes and tapeworms selectively and will function as carriers of suitable radio-isotopes, such as Cu-64, for treating colon cancers when attached to appropriate monoclonal antibodies.

The amino acid chemistry in References [3] and [4] describe novel and simple methods of synthesising new amino acids and elaborating existing ones. In some instances, the derivatives may function as suicide substrates to impede undesirable enzyme pathways. In other instances, novel new polyamine derivatives have been made which may influence the replication of DNA and potentially at least influence the decay of abnormal cells relative to normal cells.

[1] Sargeson. A.M. The potential for the cage complexes in biology. Coord. Chem. Rev. 151, 89-114 (1996). (Proceedings of the ISABC-3 Symposium, Fremantle (1994). Ed. A.B.P. Lever, Elsevier Science S.A., Lausanne, Switzerland).

[2] Dibartolo, N.M., Sargeson, A.M., Donlevy, T.M., Smith, S.V. Synthesis of a new cage ligand, SarAr, and its complexation with selected transition metal ions for potential use in radioimaging. J. Chem. Soc., Dalton Trans. 2303-2309 (2001).

[3] Barfod, R., Bendahl, L., Hammershøi, A., Kjærgaard-Jensen, D., Sargeson, A.M., Willis, A.C. Novel metal complex synthons for chiral 4-azaleucine, 2,3 diamino-propionic acid and its elaboration. J. Chem. Soc., Dalton Trans. 449-457 (1999).

[4] Laval, G., Clegg, W., Crane, C.G., Hammershøi, A., Sargeson, A.M., Golding, B.T. Assembly of polyamines via amino acids from three components using cobalt(III) template methodology. Chem. Commun. 1874-1875 (2002).