AB-INITIO CALCULATIONS ON NEUTRAL AND ALKALINE HYDROLYZES OF BETA-LACTAM ANTIBIOTICS - A THEORETICAL-STUDY INCLUDING SOLVENT EFFECTS

In this work we present a theoretical study of neutral and alkaline hy drolyses of N-methylazetidinone as a model of biological hydrolysis of beta-lactam antibiotics. Calculations have been carried out at the HF and MP2 levels using the 3-21G, 6-31G, and 6-31+G* basis sets. Solve nt effects have been included by means of a polarizable continuum mode l. Our results indicate two possible reaction mechanisms for the beta- lactam hydrolysis: concerted and stepwise. In both the neutral and alk aline hydrolyses the concerted mechanism presents a free energy barrie r lower than that of the stepwise mechanism.