DFT calculations based on the hybrid functional B3LYP/6-31+G* were used to study the alkaline hydrolysis of an aza-clavulanic acid, which results from the substitution of the carbon atom at position 6 in clavulanic acid by a nitrogen atom. The presence of the nitrogen atom endows the compound with special properties; in fact, once formed, the tetrahedral intermediate can evolve with cleavage of the N-4-C-7 or N-6-C-7 bond, which obviously leads to different reaction products. These differential bond cleavages may play a central role in the inactivation of beta-lactamases, so the compound may be a powerful inactivator of these enzymes. (C) 2003 Elsevier Science B.V. All rights reserved.