Hydration Structure of Cocaine and its Metabolites: A Molecular Dynamics Study

Abstract

We present molecular dynamics simulations of solvated cocaine and its metabolites in water, using both the Optimized Potentials for Liquid Simulations (OPLS) force field and the same force field but with Quantum Theory of Atoms In Molecules (QTAIM) atomic charges. We focus on the microscopic aspects of solvation, e.g. hydrogen bonds, and investigate influence of partial charges applied. Hydrophobicity or hydrophicility of these molecules were analyzed in terms of solute–solvent radial distribution functions and, for their most hydrophilic atoms, by spatial density functions. These hydration studies allowed us to classify these molecules according to their total coordination numbers, from the most hydrated metabolite to least hydrated, and this trend matches the degree of each metabolite is excreted in urine of patients with a high consumption of cocaine. Finally, we observed that QTAIM charges provide a more physically reasonable description of electrostatic environment of these solvated molecules than those of OPLS charges.