AB Initio Quantum Chemical Approach to the Antibiotic Activity of β-Lactams

Abstract

Quantum chemical investigations of the base-catalysed breaking of the endocyclic amide bond of some β-lactams are presented and discussed through ab initio Hartree-Fock calculations of the potential energy surfaces of the β-lactam + OH–, CH3O-β-lactam+OH–, and 3-cephem+OH– reactions. The initial attack of the nucleophile is similar for each reaction and gives a tetrahedral intermediate. The breaking of the amide bond occurs with a reaction barrier which is remarkably lower in 3-cephem than in the monocyclic β-lactams owing to the electron-withdrawing effect of the enamine group. The product is stabilized by an intramolecular hydrogen bond and its energy depends on intramolecular steric interactions. The theoretical results are correlated with some experimental data on the antibiotic activity of β-lactams.