A quantum mechanical and molecular mechanical method based on CM1A charges: Applications to solvent effects on organic equilibria and reactions

A combined quantum mechanical and molecular mechanical method is presented and tested through Monte Carlo statistical mechanics simulations. The method is general and computationally efficient for obtaining energetic and structural results for organic processes in the liquid phase. The solutes are represented quantum mechanically through AM1 calculations, and the solvent is treated explicitly with classical OPLS potential functions. The interaction between the quantum and classical parts of the systems is computed classically using scaled partial charges for the solute atoms that are derived from the AM1 wave function via the CM1A procedure of Cramer and Truhlar. The new methodology is tested through computation of free energies of hydration of thirteen diverse organic molecules, the medium dependence of the conformational equilibria for 1,2-dichloroethane and furfural, the acceleration of the Claisen rearrangement of allyl vinyl ether in water, and the medium dependence of the tautomeric equilibrium for 2-hydroxypyridine and 2-pyridone.