Semiempirical and ab initio calculations on the alkaline hydrolysis of the β-lactam ring Influence of the solvent

Abstract We used semiempirical and ab initio calculations to investigate the nucleophilic attack of the hydroxyl ion on the β-lactam carbonyl group. Both allowed us to detect reaction intermediates pertaining to proton-transfer reactions. We also used ab initio calculations and the PM3 semiempirical method to investigate the influence of the solvent on the process. The AMSOL method predicts the occurrence of a potential energy barrier of 20.7 kcal mol −1 due to the desolvation of the hydroxyl ion in approaching the β-lactam carbonyl group. Using the supermolecular approach and a water solvation sphere of 20 molecules around the solute, the potential energy barrier is lowered to 17.5 kcal mol −1 . Ab initio calculations using the SCRF method predict a potential energy barrier of 13.6 kcal mol −1 . These three values, especially the last two, are very close to the experimental value of 16.7 kcal mol −1 .