Hybrid approach for free energy calculations with high-level methods: application to the SN2 reaction of CHCl3 and OH- in water

J Chem Phys. 2007 Aug 7;127(5):051102. doi: 10.1063/1.2768343.

Abstract

We present an approach to calculate the free energy profile along a condensed-phase reaction path based on high-level electronic structure methods for the reactive region. The bulk of statistical averaging is shifted toward less expensive descriptions by using a hierarchy of representations that includes molecular mechanics, density functional theory, and coupled cluster theories. As an application of this approach we study the reaction of CHCl3 with OH- in aqueous solution.