Structural and Mechanistic Chemistry

Significant Achievements, Anticipated Outcomes and Future Work

Free Radical Chemistry. 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 radical addition reactions and radical abstraction reactions, both of which are very important in biological chemistry and polymer chemistry. A particularly important application has been concerned with gaining a better understanding of the RAFT polymerization process with the ultimate aim of improved process control.

Oxidative Damage to Proteins. 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 ab initio molecular orbital 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

Oxides and Hydroxides of Alkali and Alkaline Earth Metals. We have been examining the alkali metal oxides and hydroxides as a preliminary to investigating their interesting acid and base properties. Reliable experimental data are very sparse for these molecules. Their theoretical description is not entirely straightforward either and has necessitated incorporation of several new features and the development of new basis sets.

Enzyme-catalysed Reactions. Vitamin B12 is one of nature's essential vitamins. We have used ab initio calculations to model reactions mediated by coenzyme B12. Although these reactions have been extensively studied experimentally, there is certainly no consensus as to how they proceed. We find 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. Supporting evidence for our proposals has come from site-directed mutagenesis experiments. This and other recent examples provide strong encouragement for the use of computer calculations in a predictive manner in the study of enzyme reactions. Our most recent studies are being directed at the abstraction steps in these B12-mediated reactions.

Development of Improved Theoretical Procedures. The ability to predict reliable thermochemistry represents a very important application of ab initio molecular orbital theory. 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 methods that we have designated G3-RAD, G3X-RAD, G3(MP2)-RAD and G3X(MP2)-RAD.

Interaction of Metal Ions With Biological Systems. Metal ions are of great importance in biological function. We have embarked on a theoretical study to probe the interaction of metal ions with prototypical biological molecules. Our initial studies 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.

Computational Techniques Used

We use mainstream computational quantum chemistry programs for our work. These have generally been refined by APAC National Facility / ANUSF programmers and are also tested within my research group. The main programs that we use are GAUSSIAN, MOLPRO, ACES2 and QCHEM. The substantial computing power of the APAC National Facility has made possible calculations on larger molecules and the use of more reliable theoretical procedures. Such computing power is a necessary requirement for carrying out internationally competitive research.

Publications, Awards and External Funding

External Funding and Awards

ARC Discovery grant.

2003 Lise Meitner Lecturer, Hebrew University Jerusalem.

2003 Dozor Lecturer, Ben Gurion University, Beer Sheva, Israel.

Publications

M.L. Coote, L. Radom, Ab Initio Evidence for Slow Fragmentation in RAFT Polymerization, Journal of the American Chemical Society, 125, 2003,1490–1491.

D.J. Henry, M.B. Sullivan, L. Radom, G3-RAD and G3X-RAD: Modified Gaussian-3 (G3) and Gaussian-3X (G3X) Procedures for Radical Thermochemistry, Journal of Chemical Physics, 118, 2003, 4849–4860.

A. Rauk, R.J. Boyd, S.L. Boyd, D.J. Henry, L. Radom, Alkoxy Radicals in the Gaseous Phase: b-Scission Reactions and Formation by Radical Addition to Carbonyl Compounds, Canadian Journal of Chemistry, 81, 2003, 431–442.

M.L. Coote, M.A. Collins, L. Radom, Calculation of Accurate Imaginary Frequencies and Tunnelling Coefficients for Hydrogen Abstraction Reactions using IRCmax, Molecular Physics, 101, 2003, 1329–1338.

M.A. Collins, L. Radom, Proton-Transport Catalysis, Proton Abstraction and Proton Exchange in HF + HOC+ and H2O + HOC+ and Analogous Deuterated Reactions, Journal of Chemical Physics, 118, 2003, 6222–6229.

A.K. Croft, C.J. Easton, L. Radom, Design of Radical-Resistant Amino Acid Residues: A Combined Theoretical and Experimental Investigation, Journal of the American Chemical Society, 125, 2003, 4119–4124.

D.J. Henry, A.L.J. Beckwith, L. Radom, Homo-Anomeric Effect in the 1,2-Dimethoxyethyl Radical, Australian journal of Chemistry, 56, 2003, 429–436.

M.B. Sullivan, M.A. Iron, P.C. Redfern, J.M.L. Martin, L.A. Curtiss, L. Radom, Heats of Formation of Alkali Metal and Alkaline Earth Metal Oxides and Hydroxides: Surprisingly Demanding Targets for High-Level Ab Initio Procedures, Journal of Physical Chemistry A, 107, 2003, 5617–5630.

C. Barner-Kowollik, M.L. Coote, T.P. Davis, L. Radom, P. Vana, The Reversible Addition-Fragmentation Chain Transfer Process and the Strength and Limitations of Modeling: Comment on "The Magnitude of the Fragmentation Rate Coefficient", Journal of Polymer Science Part A, 41, 2003, 2828–2832.

R. Gómez-Balderas, M.L. Coote, D.J. Henry, H. Fischer, L. Radom, What is the Origin of the Contrathermodynamic Behavior in Methyl Radical Addition to Alkynes versus Alkenes? Journal of Physical Chemistry A, 107, 2003, 6082–6090.

A.K. Croft, C.J. Easton, K. Kociuba, L. Radom, Strategic Use of Amino Acid N-Substituents to Limit a-Carbon-Centered Radical Formation and Consequent Loss of Stereochemical Integrity, Tetrahedron Asymmetry, 14, 2003, 2919–2926.

G.P.F. Wood, D.J. Henry, L. Radom, Performance of the RB3-LYP, RMP2 and UCCSD(T) Procedures in Calculating Radical Stabilization Energies for •NHX Radicals, Journal of Physical Chemistry A, 107, 2003, 7985–7990.

I. Corral, O. Mó, M. Yáñez, A.P. Scott, L. Radom. Interactions Between Neutral Molecules and Ca2+: An Assessment of Theoretical Procedures, Journal of Physical Chemistry A, 107, 2003, 10456–10461.

M.L. Coote, A. Pross, L. Radom, Variable Trends in R–X Bond Dissociation Energies (R = Me, Et, iso-Pr, tert-Bu), Organic Letters, 5, 2003, 4689–4692.