Kinetics and mechanism of zinc ion-mediated degradation of cephalosporins in tromethamine solution.

Earlier studies of the hydrolysis and aminolysis of penicillin, in the presence of zinc ion and tromethamine (Tris), revealed a very rapid catalysis mediated by a ternary complex in which the metal ion brought the reactants into close proximity in a suitable configuration for reaction. In the present work similar studies with a group of cephalosporins show not only much slower rates of reaction but a different mechanism in which the zinc ion-tromethamine complex functions as a nucleophile in a bimolecular reaction. Evidence for the differences in mechanism includes not only the different dependence of rate upon tromethamine concentration, but comparable rates of reaction of methyl esters of a penicillin and a cephalosporin and the reaction products observed by high-performance liquid chromatography.