A general methodology for quantum modeling of free-energy profile of reactions in solution: An application to the Menshutkin NH3+CH3Cl reaction in water

Abstract

We present a general methodology for calculating free-energy profile of reaction in solution using quantum mechanical methods coupled with the dielectric continuum solvation approach. Particularly, the generalized conductorlike screening model (GCOSMO) was employed in this study, though any continuum model with existing free-energy derivatives could also be used. Free-energy profile is defined as the steepest descent path from the transition state to the reactant and product channels on the liquid-phase free-energy surface. Application of this methodology to calculate the free-energy profile of the Menshutkin NH3+CH3Cl reaction in water is discussed. The efficiency of the GCOSMO method allows characterization of stationary points and determination of reaction paths to be carried out at less than 20% additional computational cost compared to gas-phase calculations. Excellent agreement between the present results and previous Monte Carlo simulations using a combined quantum mechanical/molecular mechanics (QM/MM) potential confirms the accuracy and usefulness of the GCOSMO model.