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The platinum(iv) complexes cis,trans,cis-PtIV(RNH2)(NH3)(OH)2Cl2, where R is 2,2,6,6-tetramethyl-1-oxyl-4-piperidinyl (1) or 2,2,5,5-tetramethyl-1-oxyl-3-pyrrolidinyl (2), were prepared by oxidation of the corresponding cis-PtII(RNH2)(NH3)Cl2 complexes with hydrogen peroxide. The reactions are catalyzed by tungstate salts, which makes it possible to carry out oxidation under mild conditions. The resulting complexes were characterized by elemental analysis, HPLC, and IR, UV, and ESR spectroscopy. The structure of complex 1 was established by X-ray diffraction analysis. Complex 1 exhibits the highest antitumor activity in an experimental tumor, viz., in P388 leukemia. The resistance of the tumor to this complex developed much slower than that to Cisplatin.

Mixed-ligand platinum complexescis-PtII(R6NH2)(NH3)X2 andcis-PtII(R5NH2)(NH3)X2 (R6 is 2,2,6,6-tetramethyl-4-piperidyl-1-oxyl and R5 is 2,2,5,5-tetramethyl-3-pyrrolidinyl-1-oxyl) were synthesized by either the reaction of aminonitroxides RNH2 with Na[PtII(NH3)Cl2I] generatedin situ (for X2=ClI) or by replacement of the iodo-chloro ligands incis-Pt11(RNH2)(NH3)ClI by dichloro and oxalato ligands. The complexes obtained were characterized by elemental analysis and by IR, UV, and ESR spectra. Forcis-Pt11(R5NH2)(NH3)Cl2, crystal and molecular structures were determined by X-ray diffraction analysis. Cisplatin accelerates autooxidation of methyl linoleate and the platinum nitroxide complexes synthesized exhibit antioxidant properties. The rate of isolated DNA binding with the new complexes is almost as high as that for cisplatin.cis-Pt11(R6NH2)(NH3)Cl2 exhibits the highest antitumor activity. The high antitumor activity of platinum nitroxide complexes shows that the possible “radical component” is not a crucial factor in the cytotoxic action of cisplatin.