REACTION OF CIS-[PTCL2(NH3)2] AND TRANS-[PTCL2(NH3)2] WITH REDUCED GLUTATHIONE STUDIED BY H-1-[H-1], C-13[H-1], PT-195[H-1] AND N-15-[H-1] DEPT NMR

The products of the reactions of cis- and trans-[PtCl2(NH3)2] with reduced glutathione (GSH) in phosphate-buffer (pH 7) have been characterized by 1H, 13C, 15N and 195Pt NMR, with the aim of identifying the likely metabolites of the complexes with intracellular GSH. The final product of the reaction of trans-[PtCl2(NH3)2] with GSH was the bis-substituted complex trans-[Pt(SG)2(NH3)2] in which glutathione was coordinated exclusively via the S atom. Trans-[Pt(SG)Cl(NH3)2] was formed in the first step and reacted either with GSH to form trans-[Pt(SG)2(NH3)2], or with trans-[PtCl2(NH3)2] to give the S-bridged complex trans-[{(NH3)2PtCl}2SG]+. This reacted with GSH regenerating trans-[Pt(SG)Cl(NH3)2]. By the use of a 15N-{1H} DEPT pulse sequence, 15N NMR was used to follow the transient intermediates of the reaction of cis-[PtCl2(15NH3)2] with GSH. The mono-substituted complex cis-[PtCl(SG)(15NH3)2] was formed first, but several other species containing a 15NH3-Pt-S linkage were present within a few minutes of starting the reaction. 15NH3 ligands began to be released within 10 min and the final product contained no coordinated 15NH3. The 1H, 13C, and 195Pt NMR spectra of the final product were consistent with a high-molecular weight polymer with a 1:2 Pt:GSH stoichiometry, in which coordination was almost exclusively via the S atom, but with several different Pt-S and Pt-S-Pt environments. © 1990.