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.