Transition-state optimization by the free energy gradient method: Application to aqueous-phase Menshutkin reaction between ammonia and methyl chloride

yThe transition state (TS) for the Menshutkin reaction H3N + CH3Cl --> H3NC H3+ + Cl- in aqueous solution was located on the free energy surface (FES) by the free energy gradient (FEG) method, The solute-solvent system was des cribed by a hybrid quantum mechanical and molecular mechanical (QM/MM) meth od. The reaction path in water was found to deviate largely from that in th e gas phase. It was concluded that, in such a reaction including charge sep aration, TS structure optimization on an FES is inevitable for obtaining va lid information about a TS in solution. (C) 2001 Published by Elsevier Scie nce B.V.