Analysis of metallonucleoside hydrolysis by high-pressure liquid chromatography

Abstract

A number of ammine complexes of transition metals in the platinum group exhibit antitumor and mutagenic activities, which probably result from in vivo metal ion coordination to nucleic acids. Coordination at N-7 purine sites on nucleic acids may induce depurination through a general acid-catalyzed cleavage of the sugar-purine bond. This possibility was tested by observing the hydrolysis of [dGuo)(NH 3) 5Ru] 3+ under physiological conditions. Since multiple products result from this reaction, a high-pressure liquid chromatography technique was developed for separating various ammineruthenium(III) complexes with purine, pyrimidine, and nucleoside ligands. Using this technique it was possible to identify and follow the relative concentrations of several of the hydrolysis products. These data were used to develop a preliminary reaction scheme for the decomposition of (dGuo)(NH 3) 5Ru(III). The net rate constant (1.8 × 10 −6 s −1) for the disappearance of this complex yields an upper limit for the rate of metal-induced sugar hydrolysis. While the half-life ( 5 days < t 1 2 < 28 days ) for the sugar hydrolysis reaction is substantially shorter than that for the free nucleoside under the same conditions, it cannot be concluded that this represents a major contribution to the mutagenicity of Ru(III) complexes.