Solvation effects on the S(N)2 reaction between CH3Cl and Cl- in water

Car-Parrinello molecular dynamics simulations have been performed to invest igate the solvation effects on the prototype S(N)2 reaction between Cl- and CH3Cl. The free energy barrier for this reaction in water was calculated u sing constrained dynamics at a constant temperature of 300 K and constant v olume. Calculations on the isolated system (reaction in the gas phase at ze ro temperature) were performed for reference purposes. Qualitatively, the c alculations confirm that the double-well free energy profile of the reactio n in the gas phase is converted into a single barrier by solvation and that the height of the barrier increases significantly. Quantitatively, there a re two error sources. At the electronic structure side, the Becke-Perdew fu nctional underestimates the barrier height by 8 kcal/mol. At the dynamics s ide, there is a "hysteresis" effect-too slow an adaptation of the solvent s tructure to changes in the reaction coordinate-yielding an estimated error of 3 kcal/mol in the free energy barrier height. After correction for these errors, the calculated value of the free energy barrier is 27 kcal/mol. Co nsidering the accuracy of the solvent-solvent and solvent-reactant interact ions of ca. 1 kcal/mol, this compares very well with the experimental estim ate of 26.6 kcal/mol. This indicates that the ab initio (DFT) MD very well captures the differential energetic as well as entropic effects of the solv ation when going from the (solvated) reactants to the initial ion-dipole co mplex to the transition state.