Ab initio study of the chemical reactivity of oxo-b-lactam structure

• Various mechanisms for the alkaline hydrolysis of oxo-b-lactam compound were analyzed on the basis of RHF/6-31+G*//RHF/6-31+G* calculations in order to identify potential differences with classical b-lactam antibiotics. Changes in the tetrahedral intermediate were studied via the cleavage not only of the bond between atoms at 7 and 4 as in classical b-lactam antibiotics but also of that between those at 7 and 6, which was previously put forward as a plausible pathway for the hydrolysis of these compounds. Cleavage of the 7–6 bond was found to be the energetically more favorable pathway in this compound. Opening of the b-lactam ring at the 7–6 bond yields especially stable carbamates, which suggests a potential inhibitory action in serine-b-lactamases. Based on the computations, those hydrolysis products where the five-membered ring is opened by cleavage of the C₅–S₁ bond are highly stable.