Metal-ion catalysed hydrolysis of some β-lactam antibiotics

Abstract

The metal(II)-ion catalysed hydrolysis of some pencillin and cephalosporin derivatives in water at 30° shows saturation kinetics. A 1 : 1 complex is formed between the metal ion and penicillin which is attacked by hydroxide ion up to 10⁸ fold faster than the unco-ordinated compound. The site of co-ordination of the penicillins and copper(II) ions is the β-lactam nitrogen and the carboxylate group. The association constants for the cephalosporins and metal ions are greater than those for the penicillins but the transition states for the cephalosporin reaction with hydroxide ion bind less tightly to metal ions. The order of rate enhancement brought about by the metal ion is Cu^II > Zn^II > Ni^II∼ Co^II. The metal ions are thought to stabilise the tetrahedral intermediate formed by hydroxide ion attack on the β-lactam. Some comments are made about metal ions as electrophilic catalysts in enzymes.