A multilayered-representation, quantum mechanical/molecular mechanics study of the CH3Cl + F− reaction in aqueous solution: the reaction mechanism, solvent effects and potential of mean force

Abstract

A multilayered-representation, quantum mechanical and molecular mechanics approach was employed to study the bimolecular nucleophilic substitution reaction of CH₃Cl + F⁻ in aqueous solution. The affected reactant complex, the transition state and the product complex, in the presence of the aqueous solution, were analyzed along the reaction pathway. A multilayered representation which includes the density functional theory and coupled-cluster single double (triple) (CCSD(T)) theories for the reaction region was used to compute the potentials of mean force for this reaction in aqueous solution. The obtained free energy activation barrier under the CCSD(T)/MM representation is 23.2 kcal mol⁻¹, which agrees well with the experimental value of 26.9 kcal mol⁻¹. The calculated reaction free energy, −8.0 kcal mol⁻¹, has an excellent agreement with the estimated value, −8.1 kcal mol⁻¹, in solution obtained based on the solvation energies and reaction energy in the gas phase. The solvation energy increases the activation barrier by 17.0 kcal mol⁻¹, while the polarization effect increases the activation barrier only by 1.5 kcal mol⁻¹. All in all, the aqueous solution plays an essential role in shaping the reaction pathway for this reaction in water.