A COMPUTATIONALLY EFFICIENT PROCEDURE FOR MODELING THE FIRST STEP IN THE ALKALINE-HYDROLYSIS OF ESTERS

A computationally efficient procedure for modeling the alkaline hydrol ysis of esters is proposed based on calculations performed on methyl a cetate and methyl benzoate systems. Extensive geometry and energy comp arisons were performed on the simple ester methyl acetate. The effecti veness of performing high level single point ab initio energy calculat ions on the geometries obtained from semiempirical and ab initio metho ds was determined. The AM1 and PM3 semiempirical methods are evaluated for their ability to model the transition states and intermediates fo r ester hydrolysis. The Cramer/Truhlar SM3 solvation method was used t o determine activation energies. The most computationally efficient wa y to model the transition states of large esters is to use the PM3 met hod. The PM3 transition structure can then be used as a template for t he design of haptens capable of inducing catalytic antibodies. (C) 199 5 John Wiley & Sons, Inc.