Ab initio and Monte Carlo calculations for a nucleophilic addition reaction in the gas phase and in aqueous solution

Abstract

Energy profiles for the nucleophilic addition of hydroxide ion to formaldehyde in the gas phase and in aqueous solution have been determined with quantum and statistical mechanical methods. Ab initio calculations at the 6-31+G* level were utilized to study the gas-phase potential energy surface. In the gas phase, the conversion of reactants to the tetrahedral intermediate is exothermic by 35 kcal/mol and proceeds via an ion-dipole complex. Monte Carlo simulations were then carried out for the reacting system solvated by 269 water molecules at 25/sup 0/C and 1 atm with solute-solvent potential functions derived from ab initio calculations in conjunction with the TIP4P model of water. Importance sampling methods were employed to obtain the potential of mean force in solution. A substantial activation barrier is introduced by hydration with the transition state occurring at a C-O separation of ca. 2 A. The calculated height of the free energy barrier is 24-28 kcal/mol and the tetrahedral intermediate is 10-14 kcal/mol above the reactants. Finally, fixed solute simulations corresponding to the reactants, transition state, and product were carried out to probe the origin of the activation barrier.