MODELING NUCLEOPHILIC-ATTACK ON BETA-LACTAM ANTIBIOTICS - A PM3 STUDY

In the present paper, the nucleophilic attack on the beta-lactamic bon d in antibiotics is studied using the MNDO-PM3 semiempirical quantum m echanical approach and full optimization of the molecular geometry. Fo r this purpose Boyd's models of penicillins and cephalosporins are ado pted, taking into account the presence of the amidic group in position 3. The penicillin model, and especially the cephalosporin one, are fo und to be more reactive towards breaking the beta-lactamic bond than t he reference model for two main reasons: the lower formation energy of the tetrahedric intermediates, and the lower energy barriers on reach ing the final products.