Metal ion catalysis in the aminolysis of penicillin

Abstract
The copper(II) ion catalysed hydrolysis and aminolysis of benzylpenicillin in water at 30° shows saturation kinetics. A 1 : 1 complex is formed between the metal ion and benzylpenicillin which is attacked by hydroxide ion and amine ca. 107-fold faster than unco-ordinated benzylpenicilin. The Brønsted β value for nucleophilic attack by amines is 0.87. The copper(II)ion catalysed reactions of the methyl ester of benzylpenicillin show much smaller rate enhancements indicating that the site of co-ordination for the antibiotic involves the ionised carboxy-group. The mechanism of the catalysed reactions does not involve the intermediate formation of benzylpenicillenic acid or a keten. The reactions are inhibited by buffers which co-ordinate to copper(II)ions. Trifluoroethylamine forms a 1 : 1 complex with copper(II) ion with an equilibrium constant of 15.6 l mol–1.
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