Quantum mechanical and molecular mechanics approach with a multilayered-quantum representation study of solvent effects and potentials of mean force for the CH3CH2Cl + ClO− SN2 reaction in aqueous solution

The bimolecular nucleophilic substitution reaction of CH3CH2Cl + ClO− in aqueous solution was investigated using a multilayered-quantum representation, quantum mechanical and molecular mechanics approach with an explicit water model. Ten configurations along the reaction pathway including reactant complex, transition state and product complex were analyzed in the presence of the aqueous solution. The obtained free energy activation barrier under the CCSD(T)/MM representation is 13.2 kcal/mol, while it is 11.7 kcal/mol under the DFT/MM representation which agrees very well with the DFT calculation, at 11.0 kcal/mol, with a polarizable continuum solvent model. The solvent effects including the solvation free energy contribution and the polarization effect raise the free activation barrier by 9.8 kcal/mol. The rate constant, at 298 K, is 5.27 × 10−17 cm3/molecule/s which is about seven orders of magnitude smaller than that in the gas phase (1.10 × 10−10 cm3/molecule/s). All in all, the aqueous solution plays an essential role in shaping the reaction pathway for this reaction in water.