The Pt–S bond of Pt(II)–glutathione (GS–Pt) complex was dissociable in neutral phosphate buffer at room temperature in the presence of Cu(II) ion. In addition, the chloro species, Pt(terpy)Cl+, was isolated and identified as the major cleavage product of Pt(terpy)(GS)2+ complex when CuCl2 was used. The Pt–S bond dissociation of Pt(terpy)(GS)2+ mediated by Cu(II) ion was shown to be a pH dependent process in the range of 4.5–8.0. At pH <7, NMR evidence was obtained for a S-bridged heterodinuclear unit formed between Pt(terpy)(GS)2+ and the Cu(II) ion; however, no Pt–S bond dissociation was observed up to 24 h. At pH ⩾ 7, NMR data suggested coordination of the amide nitrogen of GSH of Pt(terpy)(GS)2+ to the Cu(II) ion. We propose that the coordination of the amide nitrogen to the Cu(II) ion, together with the formation of the S-bridged heterodinuclear unit, induce the Pt–S bond dissociation in Pt(terpy)(GS)2+. These results may be exploited to develop a molecular activator to regenerate the anticancer activity in cisplatin pro-drugs.
Journal of inorganic biochemistry 71(3-4), pp.109-113