Studies on clavulanic acid. Part 2. The catalytic effect of metal ions on the hydrolysis of clavulanic acid

Abstract

The metal (II)-ion-catalysed hydrolysis of clavulanic acid in water shows saturation kinetics. A 1:1 complex is formed between the metal ion and clavulanic acid, which is attacked by hydroxide ion ca. 2 × 10⁶ times as fast as the unco-ordinated clavulanic acid. The catalytic effect produced by the copper(II) ion on the decomposition of the methyl ester of clavulanic acid shows a much smaller rate enhancement, indicating that the site of co-ordination for the clavulanic acid involves the ionized carboxylate group. The co-ordination sites of the clavulanic acid are the β-lactam nitrogen and the carboxylate group. The association constants between clavulanate ion and several transition metal ions have been determined. The order of rate enhancement brought about by the metal ion is Cu^II > Zn^II > Cd^II > Co^II > Ni^II > Mn^II. The reaction is inhibited by the presence of anions co-ordinating with the copper(II) ion.