Reactions of [PtCl(dien)]Cl with glutathione, oxidized glutathione and S-methyl glutathione. Formation of an S-bridged dinuclear unit

Abstract

The reaction of the monofunctional platinum compound [PtCl(dien)]Cl with the tripeptide glutathione (GSH), oxidized glutathione (GSSG) and S-methyl glutathione (GS-Me) has been investigated by 1H, 13C and 195Pt magnetic resonance spectroscopy and by potentiometric titrations. It appears that platinum binds with a high degree of specificity to the GSH sulfhydryl group. The reaction of platinum with GSH proceeds in two steps. In the first step only one platinum binds to the sulfur atom and, in the second step, another [Pt(dien)] 2+ unit binds to [Pt(dien)GS] + forming an S-bridged dinuclear unit [{Pt(dien)} 2GS] 3+. The rate of the first binding step is pH-dependent, whereas the rate of the second step is not. At pH < 7 the rate of the first binding step is slow compared to the rate of the second binding step. At pH > 10, on the other hand, the rate of the first binding step is faster than the rate of the second binding step. Consequently, at pH < 7 one can only isolate the [{Pt(dien)} 2GS] 3+ complex. In the presence of free GSH, at pH > 7, one [Pt(dien)] 2+ unit of [{Pt(dien)} 2GS] 3+ dissociates forming [Pt(dien)GS] +. The mechanism of the pH-dependent rate of the first platinum binding step and the ligand-exchange reaction are discussed. GSSG reacts with [Pt(dien)] 2+, also forming the S-bridged dinuclear unit [{Pt(dien)} 2GS] 3+, probably through a redox disproportionation reaction with a catalytic function of [PtCl(dien)]Cl. GS-Me reacts with [Pt(dien)] 2+ forming the S-coordinated [Pt(dien)GS-Me] 2+. [Pt(dien)GS-Me] 2+ exists as a pair of diastereomers due to different configurations about sulfur. The rate of the inversion of configuration at the coordinated sulfur atom is slow on the NMR time-scale.