Alterations in the Binding of [Cl(NH3)5RuIII]2+ to DNA by Glutathione: Reduction, Autoxidation, Coordination, and Decomposition

Abstract

The autoxidation of glutathione (GSH) is catalyzed by [Cl(NH3)5RuIII]2+ yielding only [OH(NH3)5RuIII]2+ and GSSG according to the rate law d[GSSG]/dt = k[Ru][GSH], where k = 3 M-1 s-1. The anaerobic reaction of GSH with [Cl(NH3)5RuIII]2+ yields first [OH(NH3)5RuIII]2+ and then [GS(NH3)5RuIII]+ at neutral pH, both through redox catalysis. The reaction appears to proceed through reduction of RuIII by GSH to give [H2O(NH3)5RuII]2+, followed by coordination to produce [GSH(NH3)5RuII]2+ and then oxidation of the latter ion by [OH(NH3)5RuIII]2+ or GSSG to yield [GS(NH3)5RuIII]+. [GS(NH3)5RuIII]+ is also produced by the reaction of GSH with [(NH3)6Ru]3+ or [py(NH3)5Ru]3+. Glutathione reduces [OH(NH3)5RuIII]2+ through a pre-equilibrium mechanism according to the following rate law: d[RuII]/dt = k[RuIII][GSH]/(Ki + [GSH]), where Ki = 2.0 × 10-3 M-1 and k = 2.3 × 10-3 s-1. The reduction potential of [(GS)(NH3)5RuIII,] is pH-dependent according to the Nernstian equation: E = E° − 0.59log {Ka/([H+] + Ka)}, where E°...