Solvent and Secondary Kinetic Isotope Effects for the Microhydrated S_N2 Reaction of C1⁻(H₂O)_n with CH₃C1

We have calculated gas-phase rate coefficients and deuterium kinetic isotope effects (KIEs) for isotopic substitution in either the methyl group or the water of the title reaction with n = 1 and 2. The calculations are carried out by variational transition-state theory with semiclassical transmission coefficients, and they are based on 27− and 36-dimensional reaction-path potentials presented previously. A critical aspect of the potentials is that the solute part is based on high-level ab initio calculations. We also analyze the effect of deuterium substitution at methyl for the case of n = 0. We calculate an inverse effect for substitution at methyl both for bare solute (n = 0) and for microhydrated solute with n = 1 or 2. A detailed mode analysis shows that the inverse effect for the unhydrated reaction is dominated by C–H stretch contributions rather than by CH₃ deformations as is usually assumed in analyzing experimental data on solution-phase reactions. Furthermore, the C–H stretch contribution to the inverse a-deuterium KIE is essentially unaffected by microhydration. We find that for n = 1 the secondary KIE for substitution at methyl is larger than the solvent KIE, but for n = 2 the trend is reversed. The solvent KIEs are also interpreted in terms of the contributions of individual vibrational modes; in the n = 2 case the KIE is attributable to the breaking of a water-water hydrogen bond and the weakening of a water—chloride hydrogen bond.