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

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.