Mark M. Davidson

ROTATION ABOUT THE C-N BOND IN FORMAMIDE : AN AB INITIO MOLECULAR ORBITAL STUDY OF STRUCTURE AND ENERGETICS IN THE GAS PHASE AND IN SOLUTION

The structural and energetic changes associated with C—N bond rotation in formamide both in the gas phase and in solution have been studied theoretically using ab initio molecular orbital methods. The barrier predicted in the gas phase and in acetone are in good agreement with experimental estimates. Details of the rotation in the gas phase and in water have been studied using a new reaction-path-following technique.

The Claisen rearrangement of allyl vinyl ether in the gas phase and aqueous solution. Structures and energies predicted by high-level ab initio calculations

Abstract Structures of the reactant and transition state of the Claisen rearrangement of allyl vinyl ether are obtained at a higher level of electron correlation than previously reported, and yield a closer prediction of the activation barrier. The transition state is predicted to be more dissociative in aqueous solution than in the gas phase.

Modelling the reaction OH- + CO2 → HCO- 3 in the gas phase and in aqueous solution: a combined density functional continuum approach

Density functional theory methods combined with continuum models of solvation are used to predict the free energy profile of the reaction OH- + CO2 → HCO- 3 in aqueous solution. A barrier to the reaction is predicted with a height in good agreement with experiment, in contrast to the gas phase situation. The strategy used here may thus be of value in modelling complex reactions in the condensed phase.

The mechanism of the catalysis of the Claisen rearrangement of chorismate to prephenate by the chorismate mutase from Bacillus subtilis. A molecular mechanics and hybrid quantum mechanical/molecular mechanical study

The role of the active site of the chorismate mutase from Bacillus subtilis in catalysing the Claisen rearrangement of chorismate to prephenate is studied computationally using both molecular mechanics and a hybrid quantum mechanical/molecular mechanical method. Structures along the pathway calculated at the HF/6-31G* level are docked into the active site and reveal that the hydrogen bonding interactions reflect the changing geometry and electronic structure of the substrate. In particular the interactions are maximal close to the transition state and lead to a barrier lowering greater than that needed to produce the observed rate acceleration in line with conclusions that the chemical transformation is not the rate determining process.

Calculation of transition state structures and kinetic isotope effects in the Claisen rearrangement of allyl vinyl ether and chorismic acid

Abstract The calculated transition state for the Claisen rearrangement of chorismic acid is considerably more dissociative than that for allyl vinyl ether. The predicted kinetic isotope effects for the two reactions are in accord with experimental measurements.

CONFORMATIONAL AND SOLVATION ASPECTS OF THE CHORISMATE-PREPHENATE REARRANGEMENT STUDIED BY AB INITIO ELECTRONIC STRUCTURE AND SIMULATION METHODS

The effect of water on the energetics of the Claisen rearrangement of chorismate to prephenate has been investigated with both a continuum model (PCM) and explicit solvation within a Monte Carlo (MC) free energy perturbation (FEP) treatment. Both models are surprisingly similar in their quantitative predictions. Solvation is shown to increase the conformational flexibility in the reactant by reducing the energy difference between the diequatorial and diaxial structures, and to lead to a considerable reduction in the barrier to the reaction. The estimate of the activation barrier, 22 kcal mol-1, is very close to the experimental value of 24.5 kcal mol-1. The implications of the various possible conformers on kinetic isotope effects are discussed.

Contribution of transition-state binding to the catalytic activity of Bacillus subtilis chorismate mutase

The differential electrostatic interaction of chorismate, compared to the transition-state involved in its transformation to prephenate, with the active site of chorismate mutase, leads to a rate enhancement in line with experiment.

Claisen rearrangement of chorismic acid and related analogues: an ab initio molecular orbital study

The structure and energies of the reactant and transition state for the Claisen rearrangement of chorismic acid and related analogues have been determined using ab initio molecular orbital methods. The rate acceleration found for chorismic acid compared to that of allyl vinyl ether is attributed to both reactant destabilisation and transition state stabilisation. The electronic effects responsible for the observed rate retardation associated with the ring carboxy and hydroxy groups have been identified.