SEMIEMPIRICAL AND AB-INITIO CALCULATIONS ON THE ALKALINE-HYDROLYSIS OF THE BETA-LACTAM RING - INFLUENCE OF THE SOLVENT

We used semiempirical and ab initio calculations to investigate the nu cleophilic attack of the hydroxyl ion on the beta-lactam carbonyl grou p. Both allowed us to detect reaction intermediates pertaining to prot on-transfer reactions. We also used ab initio calculations and the PM3 semiempirical method to investigate the influence of the solvent on t he process. The AMSOL method predicts the occurrence of a potential en ergy barrier of 20.7 kcal mol(-1) due to the desolvation of the hydrox yl ion in approaching the beta-lactam carbonyl group. Using the superm olecular 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 e nergy 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).