Solvent effects and potential of mean force: a multilayered-representation quantum mechanical/molecular mechanics...

The bimolecular nucleophilic substitution (SN2) reaction of CH3Br and CN(-) in aqueous solution was investigated using a multilayered-representation quantum mechanical and molecular mechanics methodology. The reactant complex, transition state, and product complex are identified and characterized in aqueous solution. The potentials of mean force are computed at both DFT and CCSD(T) levels of theory for the reaction region. The CCSD(T)/MM level of theory presents a free energy activation barrier height at 19.1 kcal mol(-1) which agrees very well with the experimental value of 20.7 kcal mol(-1), while the DFT/MM level of theory underestimated the barrier height at 16.5 kcal mol(-1). The results show that the aqueous environment has a significant contribution to the potential of mean force. Both the solvation effect and the polarization effect increase the activation barrier height by ∼14.5 kcal mol(-1) and the solvation effect plays a major role by providing about 70% of the contribution.