Grant: Discovery Grants Program - Individual

A theory of chemistry called the quantum theory of atoms in molecules (QTAIM) has become increasingly popular among theoretical chemists in recent years. The theory interprets and predicts chemistry on the basis of a topological analysis of the electron density of molecules. The electron density can be calculated from theory and can also be observed experimentally in high-resolution X-ray crystallographic experiments (followed by a special treatment of data). In QTAIM the molecular space is partitioned into separate atomic regions allowing one to focus on *local* properties of regions in a molecule just like the mental focus of an experimental chemist on a specific functional group in a molecule. So far QTAIM has been applied mainly to molecules in their ground state equilibrium geometries. While this is an important domain of application it is insufficient for a complete understanding of molecular change, change which is what a large part of (bio)chemistry is all about. This research aims at focusing on the evolution of the electron density and its topology during molecular change: Change due to the breaking and making of chemical bonds, or due to complexation with metals, or due to external electromagnetic fields, or due to interaction with solvent. We will use QTAIM to analyze the electron density of reacting systems far from their equilibrium or transition state geometries. This exploration of full reaction paths with the means of QTAIM will yield dynamical and mechanistic information necessary to complement the static picture if one wishes to discuss reactivity. A small number of very recent isolated papers advanced similar propositions, but these lack the coherence of a dedicated research program. This proposal aims at contributing in filling this gap in knowledge by applying these ideas to a selection of important problems, examples of which include: I. The effect of metal ions and solvation on the energetics of hydrolysis of ATP (the universal cellular fuel par excellence), II. The effects of external EM fields on models of the lipid peroxidation of biomembranes, and III. The effects of external fields on the proton hopping in DNA, an accepted mechanism of spontaneous mutation.