Computational studies CPCM model

As a second example, we have determined the influence of solvation on the steric retardation of SN2 reactions of chloride with ethyl and neopentyl chlorides in water, which has recently been studied by Vayner and coworkers [91]. In their study solvent effects were examined by means of QM-MM Monte Carlo simulations as well as with the CPCM model. Solvation causes a large increase in the activation energies of these reactions, but has a very small differential effect on the ethyl and neopentyl substrates. Nevertheless, a quantitative difference was found between the stability of the transition states determined using discrete and continuum treatments of solvation, since the activation free energies for ethyl chloride and neopentyl chloride amount to 23.9 and 30.4kcalmoF1 according to MC-FEP simulations, but to 38.4 and 47.6 kcal moF1 from CPCM computations. 

Keeping in mind the intrinsic features associated with the definition of the cavity in the most popular QM-SCRF methods, it can be questioned what is the influence of the fine details of the cavity definition on the computed solvation free energies. This question has been investigated in a recent study by Takano and Houk [61], who have examined the dependence of the solvation free energies estimated for a series of 70 compounds, including neutral and charged species, on both the choice of the cavity and the level of theory used in computations within the framework of the conductor-like polarizable continuum model (CPCM). The mean absolute deviation (MAD) between calculated... 

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