Deprotonation of organic molecules in solution: study of the reaction mechanism and rate by modern techniques for simulating rare events in combination with ab-initio molecular dynamics.

Abstract

Deprotonation of organic molecules are key processes involved in the rate limiting step of many chemical and biological processes. Their reaction mechanism depends on several factors such as the nature of the acid functional group (carboxyl, hydroxyl, etc.), the substituents of the molecule, and the type of solvent. However, despite their importance, these processes remain not well understood. In this project we shall study the deprotonation of different classes of organic molecules by ab-initio simulations, elucidating also the role of substitutes of the molecules. Standard atomistic simulations techniques, such as molecular dynamics (MD), cannot be used for simulating these processes by bruteforce because of the time scale involved: deprotonation is a rare event. This problem will be overcame using modern `sampling` techniques, such as Temperature Accelerated Molecular Dynamics, the String Method, and Milestoning, adapting them to the study of deprotonation process and, more generally, chemical reactions. These techniques allow to compute the reaction rate, characterize its mechanism(s), and calculate its free energy along the reaction path (i.e. free energy barrier) of chemical reactions in realistic conditions (i.e. in solution).