A GENERAL METHODOLOGY FOR QUANTUM MODELING OF FREE-ENERGY PROFILE OF REACTIONS IN SOLUTION - AN APPLICATION TO THE MENSHUTKIN NH3+CH3CL REACTION IN WATER

We present a general methodology for calculating free-energy profile o f reaction in solution using quantum mechanical methods coupled with t he dielectric continuum solvation approach, Particularly, the generali zed conductorlike screening model (GCOSMO) was employed in this study, though any continuum model with existing free-energy derivatives coul d also be used. Free-energy profile is defined as the steepest descent path from the transition state to the reactant and product channels o n the liquid-phase free-energy surface. Application of this methodolog y to calculate the free-energy profile of the Menshutkin NH3 + CH3Cl r eaction in water is discussed. The efficiency of the GCOSMO method all ows characterization of stationary points and determination of reactio n paths to be carried out at less than 20% additional computational co st 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. (C) 1997 American Instit ute of Physics.