A multilayered representation,quantum mechanical and molecular mechanics study of the CH3F + OH− reaction in water

The bimolecular nucleophilic substitution (S_N2) reaction of CH₃F + OH^? in aqueous solution was investigated using a combined quantum mechanical and molecular mechanics approach. Reactant complex, transition state, and product complex along the reaction pathway were analyzed in water. The potentials of mean force were calculated using a multilayered representation with the DFT and CCSD(T) level of theory for the reactive region. The obtained free energy activation barrier for this reaction at the CCSD(T)/MM representation is 18.3 kcal/mol which agrees well with the experimental value at ～21.6 kcal/mol. Both the solvation effect and solute polarization effect play key roles on raising the activation barrier height in aqueous solution, with the former raising the barrier height by 3.1 kcal/mol, the latter 1.5 kcal/mol. © 2013 Wiley Periodicals, Inc.