Quadrupole Correction: From Molecular Electrostatic Potential to Free Energies of Halogen Bonding.

Abstract

Recently several molecular mechanics models of halogen bonding have been published. They describe the electrostatic potential anisotropy near the heavy halogen atom (known as a σ-hole) in different ways, ranging from an all-atom multipole expansion to a single positive extra-point charge. However, the question of a reasonable balance between the accuracy and the simplicity of the model remains open. In this work, we introduce the simplistic RESPQ electrostatics model built on the RESP charges complemented with fixed atomic quadrupoles. We show that it: (1) correctly describes the MEP anisotropy of aromatic halogen atoms, (2) improves the description of the halogen-water interaction energies in both halogen and hydrogen bonding cases, (3) provides an excellent estimation of solvation free energy differences of aromatic halogens, and (4) is compatible (with the help of multipole charge cluster approximation) with contemporary molecular modeling packages.