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

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. (c) 2007 American Institute of Physics.