Ab Initio QM/MM Simulations with a Molecular Orbital-Valence Bond (MOVB) Method: Application to an S_N2 Reaction in Water

A mixed molecular orbital and valence bond (MOVB) method is described in combined ab initio QM/MM simulations of the S_N2 reaction of Cl^- + CH₃Cl → ClCH₃ + Cl^- in water. The method is based on the construction of individual charge-localized, diabatic states using a block-localized wave function approach, followed by configuration interaction calculations to obtain the adiabatic potential energy surface. To examine the performance of the MOVB method, modern ab initio VB calculations were performed. The MOVB gas phase results are found to be in reasonable agreement in the overall potential energy surface in comparison with Hartree-Fock, MP2, and ab initio VB calculations. The only exception is that the activation energy is predicted to be about 4 kcal/mol higher in MOVB than in other methods. This is attributed to the configuration interaction procedure, which does not further optimize orbital coefficients in MOVB calculations, and it emphasizes the importance of orbital optimization in these calculations. The adiabatic ground-state potential surface can also be approximate by other quantum chemical models in Monte Carlo QM/MM simulations. At the HF/6-31G(d) level, the calculated activation free energy of 26 kcal/mol in water is in good agreement with experiment and with previous computational results. Importantly, the MOVB method allows for the solvent reaction coordinate to be used to define the reaction path in ab initio QM/MM simulations.