Synthesis, structure, and biological activity of mixed-ligand platinum(II)complexes with aminonitroxides

Mixed-ligand platinum complexes cis-Pt-11((RNH2)-N-6)(NH3)X-2 and cis-Pt-11 ((RNH2)-N-5)(NH3)X-2 (R-6 is 2,2,6,6-tetramethyl-4-piperidyl-1-oxyl and R-5 is 2,2,5,5-tetramethyl-3-pyrrolidinyl-1-oxyl) were synthesized by either t he reaction of aminonitroxides RNH2 with Na[Pt-11(NH3)CI2I] generated in si tu (for X-2 = ClI) or by replacement of the iodo-chloro ligands in Cis-Pt-1 1(RNH2)(NH3)Cll by dichloro and oxalato ligands. The complexes obtained wer e characterized by elemental analysis and by IR, UV, and ESR spectra. For C is-Pt-11((RNH2)-N-5)(NH3)Cl-2, crystal and molecular structures were determ ined by X-ray diffraction analysis. Cisplatin accelerates autooxidation of methyl linoleate and the platinum nitroxide complexes synthesized exhibit a ntioxidant properties. The rate of isolated DNA binding with the new comple xes is almost as high as that for cisplatin. cis-Pt-11((RNH2)-N-6)(NH3)Cl-2 exhibits the highest antitumor activity. The high antitumor activity of pl atinum nitroxide complexes shows that the possible "radical component" is n ot a crucial factor in the cytotoxic action of cisplatin.