The compounds [Pt(Me2phen)(acy)2](NO3)2 (1), [Pt(Me2phen)(pen)2](NO3)2, [Pt(phen)(acy)2](NO3)2
(2), and [Pt(phen)(pen)2](NO3)2, containing the bidentate 1,10-phenanthroline (phen) or 2,9-
dimethyl-1,10-phenanthroline (Me2phen, neocuproine) and the antiviral agents acyclovir (acy)
or penciclovir (pen), show different in vitro toxicity, the Me2phen complexes being appreciably
more toxic than the phen complexes. To explain the different behavior, we investigated the
reaction of complexes 1 and 2 with glutathione (ç-glutamylcysteinylglycine, GSH), a peptide
believed to play an important role in driving the cellular effects of platinum drugs. The reaction
led to different products, the phen complexes forming a stable binuclear í-thiol-bridged species
still containing the phenanthroline and the Me2phen complexes releasing the neocuproine ligand
and forming an insoluble material. In vitro tests confirmed that the greater cell toxicity of
complex 1 is due to the displacement of the neocuproine ligand by GSH. The results highlight
the great dependence of the glutathione reactivity upon relatively small changes in the platinum
coordination sphere.
