Multiscale modeling of reaction rates: application to archetypal SN2 nucleophilic substitutions

We propose an approach to the evaluation of kinetic rates of elementary chemical reactions within Kramers’ theory based on the definition of the reaction coordinate as a linear combination of nat-ural, pseudo Z-matrix, internal coordinates of the system. The element of novelty is the possibility to evaluate the friction along the reaction coordinate, within a hydrodynamic framework developed recently [Campeggio, J.et al.J. Comput. Chem. 2019, 40, 679-705]. This, in turn, allows to keep into account barrier recrossing, i.e. the transmission coefficient that is employed in cor-recting transition state theory evaluations. To test the capabilities and the flaws of the approachwe use as case studies two archetypal SN2 reactions. First, we apply the approach to the standard substitution of chloride ion to bromomethane. The rate constant at 295.15 K is evaluated to k/c○= 2.7.10-6 s-1 (with c○ = 1 M), which compares well to the experimental value of 3.3.10-6 s-1 [R. H. Bathgate, and E. A. Melwyn-Hughes, J. Chem. Soc, 1959, 2642-2648]. Then, the method is applied to the SN2 reaction of methylthiolate to dimethyl disulfide in water. In biology, such an interconversion of thiols and disulfides is an important metabolic topic still not entirelyrationalized. The predicted rate constant is k/c○ = 7.7.103 s-1. No experimental data is available for such a reaction, but it is in accord with the fact that the alkyl thiolates to dialkyl disulfides substitutions in water have been found to be fast reactions [S. M. Bachrach, J. M. Hayes, T. Daoand J. L. Mynar, Theor. Chem. Acc., 2002, 107, 266-271].