Structural and Mechanistic 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 to determine the structures of molecules and to help understand how molecules react with one another. The procedure employed is called ab initio molecular orbital theory, the term ab initio signifying that the calculations are carried out from first principles using the laws of quantum mechanics. No experimental data other than values of fundamental physical constants are used. An important feature is that the calculations can be carried out as readily for reactive or hazardous species as for normal, stable molecules. They are therefore particularly useful in cases where experimental studies might be difficult or impossible. The calculations are highly computationally intensive and the APAC National Facility has been and will continue to be extremely valuable to us. One of the major areas of current activity is to try to understand how enzymes make certain reactions go faster. Another focus is to try to better understand the chemistry of free radicals since these are of widespread importance in chemistry, biology and polymers. In addition, we are developing and assessing better procedures for obtaining accurate chemical information from such quantum chemistry computations.


Principal Investigator

Leo Radom
Computational Quantum Chemistry
RSC
ANU

Project

r54, k29, q07, q08, v56, v55, v01, s08, p03, d39

Facilities Used

PC, VPP, SC, MDSS

Co-Investigators

Justine Bennett
Thomas Buesgen
Michelle Coote
Michael Hartmann
David Henry
Rebecca Jacob
Christopher Parkinson
Danne Rasmussen
Robyn Schofield
Anthony Scott
Stefan Senger
David Smith
Michael Sullivan
Stacey Wetmore
Geoff Wood
Computational Quantum Chemistry
RSC
ANU

Mark Freitag
Mark Gordon
Chemistry
Iowa State University

Brian Smith
Structural Biology
Walter & Eliza Hall Institute

Theis Solling
Chemistry
Caltech

RFCD Codes

250699


Significant Achievements, Anticipated Outcomes and Future Work

Reactions Mediated by Coenzyme B12
Although these reactions have been extensively studied experimentally, there is certainly no consensus as to how they proceed. Our ab initio calculations show that the reactions are facilitated by partial-proton-transfer. For the reaction catalyzed by the enzyme glutamate mutase, we predicted that a specific amino acid moiety within the enzyme (Glu171) is likely to play a major role in this regard. If Glu171 is removed, the enzyme should be much less effective. Precisely such experiments have very recently been carried out in the USA and have confirmed this prediction. The reaction is slowed down by a factor of 50 when Glu171 is "mutated out". Such examples provide strong encouragement for the use of computer calculations in a predictive manner in the study of enzyme reactions.

Free Radicals
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 characterization. It turns out that the theoretical study of radicals is also not entirely straightforward. Therefore it is important to carefully assess the various theoretical methods that are to be used and make improvements where necessary before embarking on extensive application. This is a key part of our research. We have been using theory to determine radical stabilization energies, with the important aim of seeing how individual substituents stabilize or destabilize a radical centre. We have also been examining the details of radical addition and abstraction reactions, both of which are very important in biological chemistry and polymer chemistry.

Development of Improved Theoretical Procedures
The ability to predict reliable thermochemistry represents a very important application of ab initio molecular orbital theory. Much work has been done with this aim in mind. Our most recent contributions have involved developing analogues of the successful G3 technique that are capable of adequately describing systems with biradical character. The most successful of these to date is called MRG3(MP2).

Hydrogen Bonding
Hydrogen bonding is of great importance in chemical and biological systems. Previous studies have mostly focussed on hydrogen bonds involving electronegative elements, e.g., O–H•••N. We have examined instead the weaker hydrogen bonds to carbon, e.g., C–H•••N. We have carried out systematic studies aimed at identifying which types of systems will exhibit the strongest C–H•••X hydrogen bonds. The effect of electronegative substitution has been particularly targeted.

 

Computational Techniques Used

We use mainstream computational quantum chemistry programs for our work. These have generally been refined by ANUSF programmers and are also tested within my research group. The main programs that we use are GAUSSIAN 98, MOLPRO 2000, ACES2 and QCHEM. The greater computing power of the new APAC facility has made possible calculations on larger molecules and using more reliable theoretical procedures.

 

Publications, Awards and External Funding

C. J. Parkinson, P. M. Mayer and L. Radom, Cyanovinyl Radical: An Illustration of Poor Performance of Unrestricted Perturbation Theory and Density Functional Theory Procedures in Calculating Radical Stabilization Energies, Theoretical Chemistry Accounts, 102, 1999, 92–96.

T. I. Sølling and L. Radom, Exchange Reactions of Chloriranium Ions and Chlorirenium Ions: A G2 Investigation, International Journal of Mass Spectrometry, 185/186/187, 1999, 263–270.

M. L. Coote, T. P. Davis and L. Radom, The Effect of Remote Substituents in Free Radical Addition Reactions: New Evidence for the Penultimate Unit Effect, Journal of Molecular Structure, Theochem, 461-462, 1999, 91–96.

D. M. Smith, B. T. Golding and L. Radom, On the Mechanism of Action of Vitamin B12: Theoretical Studies of the 2-Methyleneglutarate-Mutase-Catalyzed Rearrangement, Journal of the American Chemical Society, 121, 1999, 1037–1044.

T. I. Sølling, S. B. Wild and L. Radom, Are Pi-Ligand Exchange Reactions of Thiirenium and Thiiranium Ions Feasible? An Ab Initio Investigation, Chemistry - A European Journal, 5, 1999, 509–514.

D. M. Smith, B. T. Golding and L. Radom, Facilitation of Enzyme-Catalyzed Reactions by Partial Proton Transfer: Application to Coenzyme B12-Dependent Methylmalonyl-CoA Mutase, Journal of the American Chemical Society, 121, 1999, 1383–1384.

A. J. Chalk and L. Radom, Ion-Transport Catalysis: Catalyzed Isomerizations of NNH+ and NNCH3+, Journal of the American Chemical Society, 121, 1999, 1574–1581.

T. I. Sølling, S. B. Wild and L. Radom, Exchange and Insertion Reactions Involving Borane Adducts of Phosphirane and Phosphirene: A G2(MP2) Ab Initio Investigation, Journal of Organometallic Chemistry, 580, 1999, 320–327.

M. L. Coote, T. P. Davis and L. Radom, Effect of the Penultimate Unit on Radical Stability and Reactivity in Free-Radical Polymerization, Macromolecules, 32, 1999, 2935–2940.

M. L. Coote, T. P. Davis and L. Radom, The Conformational Dependence of the Penultimate Unit Effect in Free-Radical Copolymerization, Macromolecules, 32, 1999, 5270–5276.

D. M. Smith, B. T. Golding and L. Radom, Towards a Consistent Mechanism for Diol-Dehydratase-Catalyzed Reactions: An Application of the Partial-Proton-Transfer Concept, Journal of the American Chemical Society, 121, 1999, 5700–5704.

D. R. Rasmussen and L. Radom, Planar Tetracoordinate Carbon in a Neutral Saturated Hydrocarbon: Theoretical Design and Characterization, Angewandte Chemie, International Edition in English, 38, 1999, 2876–2878.

S. Petrie and L. Radom, Magnesium- and Calcium- Containing Molecular Dications: A High Level Theoretical Study, International Journal of Mass Spectrometry, 192, 1999, 173–183.

A. Schulz, B. J. Smith and L. Radom, Heats of Formation of Alkali and Alkaline Earth Oxides and Hydroxides: Some Dramatic Failures of the G2 Method, Journal of Physical Chemistry A, 103, 1999, 7522–7527.

D. M. Smith, B. T. Golding and L. Radom, Understanding the Mechanism of B12-Dependent Methylmalonyl-CoA Mutase: Partial Proton-Transfer in Action, Journal of the American Chemical Society, 121, 1999, 9388–9399.

C. J. Parkinson, P. M. Mayer and L. Radom, An Assessment of Theoretical Procedures for the Calculation of Reliable Radical Stabilization Energies, Journal of the Chemical Society, Perkin Transactions. 2, 1999, 2305–2314.

T. I. Sølling, S. B. Wild and L. Radom, A G2 Ab Initio Investigation of Ligand-Exchange Reactions Involving Mono- and Bis–Adducts of the Phosphenium Ion, Inorganic Chemistry, 38, 1999, 6049–6054.

A. J. Chalk, P. M. Mayer and L. Radom, Rearrangement and Fragmentation Pathways of [C3H7Z]+ Ions (Z = NH and S): Are Ion-Neutral Complexes Important? International Journal of Mass Spectrometry, 194, 2000, 181–186.

M. L. Coote, T. P. Davis and L. Radom, Models for Free-Radical Copolymerization Propagation Kinetics, In Controlled/Living Radical Polymerization, ACS Symposium Series 768, K. Matyjaszewski, Editor, pp 82–92, American Chemical Society, Washington, DC, 2000.

M. Hartmann and L. Radom, The Acetylene-Ammonia Dimer as a Prototypical C—HoooN Hydrogen-Bonded System: An Assessment of Theoretical Procedures, Journal of Physical Chemistry A, 104, 2000, 968–973.

S. Senger and L. Radom, Zeolites as Transition-Metal-Free Hydrogenation Catalysts: A Theoretical Mechanistic Study, Journal of the American Chemical Society, 122, 2000, 2613–2620.

A. J. Chalk and L. Radom, The Involvement of Ion-Neutral Complexes in Ethylene Loss From [PhC(CH3)2]+ and its Isomers, International Journal of Mass Spectrometry, 199, 2000, 29–40.

T. I. Sølling, S. B. Wild and L. Radom, Formation of Three-Membered Phosphorus Heterocycles via Ligand-Exchange Reactions in Mono-Adducts of the Phosphenium Ion: An Ab Initio Investigation, International Journal of Mass Spectrometry, 201, 2000, 205–213.

A.P. Scott and L. Radom, Are Cumulenones Kinked? A Systematic High-Level Ab Initio Study of H2CCCO, H2CCCCO and H2CCCCCO, Journal of Molecular structure, 556, 2000, 253–261.

M. A. Collins, S. Petrie, A. J. Chalk and L. Radom, Proton-Transport Catalysis and Proton-Abstraction Reactions: An Ab Initio Dynamical Study of X + HOC+ and XH+ + CO (X = Ne, Ar and Kr), Journal of Chemical Physics, 112, 2000, 6625–6634.

D. R. Rasmussen and L. Radom, Hemispiroalkaplanes: Hydrocarbon Cage Systems with a Pyramidal-Tetracoordinate Carbon Atom and Remarkable Basicity, Chemistry – A European Journal, 6, 2000, 2470–2483.

T. I. Sølling, S. B. Wild and L. Radom, Are the Approach Directions of s and p Nucleophiles to the Sulfur Atom of Thiiranium and Thiirenium Ions Different? Chemistry – A European Journal, 6, 2000, 590–591.

S. Senger and L. Radom, Towards a Low-Barrier Transition-Metal-Free Catalysis of Hydrogenation Reactions: A Theoretical Mechanistic Study of HAlX4-Catalyzed Hydrogenations of Ethene (X = F, Cl and Br), Journal of Physical Chemistry A, 104, 2000, 7375–7385.

T. I. Sølling and L. Radom, Exchange of Cl+ Between Lone-Pair Donors and p-Donors: A Computational Study, European Mass Spectrometry, 6, 2000, 153–160.

S. D. Wetmore, D. M. Smith and L. Radom, How B6 Helps B12: The Roles of B6, B12 and the Enzymes in Aminomutase-Catalyzed Reactions, Journal of the American Chemical Society, 122, 2000, 10208–10209.

D. M. Smith, B. T. Golding and L. Radom, , Understanding the Mechanism of B12-Dependent Diol Dehydratase: A Synergistic Push-Pull Proposal, Journal of the American Chemical Society, 123, 2001, 1664-1675.

M. Hartmann, S.D. Wetmore and L. Radom, C–HoooX Hydrogen Bonds of Acetylene, Ethylene and Ethane with First- and Second-Row Hydrides, Journal of Physical Chemistry A, 105, 2001, 4470–4479.

D. M. Smith, S. D. Wetmore and L. Radom, Theoretical Studies of Coenzyme B12-Dependent Carbon-Skeleton Rearrangements, In Theoretical Biochemistry - Processes and Properties of Biological Systems, L. Ericsson Editor, pp. 183–214, Elsevier, Amsterdam, 2001.

T. I. Sølling and L. Radom, A G2 Study of SH+ Exchange Reactions Involving Lone-Pair Donors and Unsaturated Hydrocarbons, Chemistry – A European Journal, 7, 2001, 1516–1524.

H. Fischer and L. Radom, Factors Controlling the Addition of Carbon-Centered Radicals to Alkenes – An Experimental and Theoretical Perspective, Angewandte Chemie, International Edition in English, 40, 2001, 1340–1371.

S. D. Wetmore, D. M. Smith, B. T. Golding and L. Radom, , Interconversion of (S)-Glutamate and (2S,3S)-3-Methylaspartate: A Distinctive B12-Dependent Carbon-Skeleton Rearrangement, Journal of the American Chemical Society, 123, 2001, 7963–7972.

T.I. Sølling, A. Pross and L. Radom, A High-Level Ab Initio Investigation of Identity and Non-Identity Gas-Phase SN2 Reactions of Halide Ions with Halophosphines, International Journal of Mass Spectrometry, 210/211, 2001, 1–11.

D. J. Henry, C. J. Parkinson, P. M. Mayer and L. Radom, Bond Dissociation Energies and Radical Stabilization Energies Associated With Substituted Methyl Radicals, Journal of Physical Chemistry A, 105, 2001, 6750–6756.

S. D. Wetmore, D. M. Smith and L. Radom, The Enzyme Catalysis of 1,2-Amino Shifts: The Cooperative Action of B6, B12 and Aminomutases, Journal of the American Chemical Society, 123, 2001, 8678–8689.

A. P. Scott, M. S. Platz and L. Radom, Singlet-Triplet Splittings and Barriers to Wolff Rearrangement for Carbonyl Carbenes, Journal of the American Chemical Society, 123, 2001, 6069–6076.

S. D. Wetmore, D. M Smith, R. Schofield and L. Radom, A Theoretical Investigation of the Effects of Electronegative Substitution on the Strength of C–HoooN Hydrogen Bonds, Journal of Physical Chemistry A, 105, 2001, 8718–8726.

D. J. Henry and L. Radom, Theoretical Thermochemistry of Radicals, In Theoretical Thermochemistry, J. Cioslowski, Editor, pp 161–197, Kluwer, Dordrecht, 2001.

T. I. Sølling, D. M. Smith, L. Radom, M. A. Freitag and M. S. Gordon, Multi-Reference Equivalents of the G2 and G3 Methods, Journal of Chemical Physics, 115, 2001, 8758–8772.

S. D. Wetmore, D. M. Smith and L. Radom, Catalysis by a Mutant of Methylmalonyl-CoA Mutase: A Theoretical Rationalization for a Change in the Rate-Determining Step, ChemBioChem, 2, 2001, 919–922.