Metal-ion Catalysed Hydrolysis of Some β-Lactam Antibiotics

Article abstract of DOI:10.1039/P29800001725

The metal(II)-ion catalysed hydrolysis of some penicillin and cephalosporin derivatives in water at 30 deg C shows saturation kinetics.A 1:1 complex is formed between the metal ion and penicillin which is attacked by hydroxyde ion up to 1E8 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 hydroxyde 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 ca.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.