THEORETICAL CALCULATIONS OF BETA-LACTAM ANTIBIOTICS .3. AM1, MNDO, AND MINDO/3 CALCULATIONS OF HYDROLYSIS OF BETA-LACTAM COMPOUND (AZETIDIN-2-ONE RING)

Semiempirical AM1, MINDO/3, and MNDO methods have been used in the study of the alkaline hydrolysis of beta-lactam antibiotics through a base-catalyzed, acyl-cleavage, bimolecular mechanism. In this work, the hydroxyl ion has been chosen as nucleophilic agent and the azetidin-2-one ring like a model of beta-lactam antibiotic. The MINDO/3 method does not predict coffectly the energies of small rings. This, together with the fact that, like MNDO, it cannot detect the occurrence of hydrogen bonds, gives rise to uncertain estimates of energy barriers. The AM1 method can be considered the most suitable for studying the hydrolysis of beta-lactam compounds.