Environmental effects in quantum chemistry : QM/MM studies of structures, NMR properties and reactivities in extended systems

Abstract

Computational modelling of chemical systems is most easily carried out in the vacuum for single molecules. Accounting for environmental effects accurately in quantum chemical calculations, however, is often necessary for computational predictions of chemical systems to have any relevance to experiment. This PhD thesis focuses on accounting for environmental effects in quantum chemical calculations by quantum mechanics/ molecular mechanics (QM/MM) approaches, taking on diverse examples from the solid state, the liquid phase and the protein environment. The methods are applied to compute a variety of properties from transition metal NMR properties of molecular crystals and enzymes, via conformational properties of zwitterions in aqueous solution, to an intramolecular amidation reaction in peptides. Chapter 3 concerns QM/MM calculations of molecular properties in the solid state, both molecular crystals and metalloenzymes, with a focus on transition metal chemical shift and EFG properties. We demonstrate that solid-state effects on such properties in molecular crystals can be accounted for by a simple general black-box QM/MM approach. We also describe preliminary QM/MM calculations of 51V anisotropic NMR properties for a vanadium-dependent enzyme. In Chapter 4 the focus is on solvent effects on the conformational preference of a small zwitterionic molecule, 3F-γ-aminobutyric acid (3F-GABA), calculated using QM/MM molecular dynamics simulations. NMR spin-spin coupling constants in solution are also calculated. Our simulations highlight the difficulty of accounting for solvation effects well enough to achieve agreement with experimental observations. Chapter 5 concerns the reaction mechanism of an intramolecular amidation reaction in a bacterial peptide, predicted by QM/MM calculations. We predict a reaction mechanism that accounts well for the experimental observations both for the wild-type and mutants. We demonstrate that environmental effects can often be satisfactorily accounted for by QM/MM approaches, thus helping to bridge the gap between theory and experiment.