Accurate quantum chemical free energies at affordable cost

TL;DR

This paper introduces a novel method combining metadynamics and free energy perturbation to accurately compute quantum chemical free energies for reactions, demonstrated on SN2 reactions in different environments.

Contribution

A new approach that integrates metadynamics and free energy perturbation to improve the accuracy of quantum chemical free energy calculations.

Findings

Successfully applied to SN2 reaction of CH3F + Cl-

Provides accurate equilibrium and rate constants

Effective for reactions in vacuo and solvated environments

Abstract

Free energy sampling methods allow studying the full dynamics of activated processes. Unfortunately, the affordable accuracy of the potential describing the energy and forces of the system is usually rather low. Here we introduce a new method that combining metadynamics and free energy perturbation allows calculating accurate quantum chemical free energies for chemical reactions. To prove the effectiveness of this new approach we study the S N 2 reaction of CH3F + Cl- -> CH3Cl + F- in vacuo and solvated by water. Comparisons are made with harmonic transition state theory to show how this method could provide accurate equilibrium and rate constants for complex systems.