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

Article abstract of DOI:10.1007/BF02495168

Mixed-ligand platinum complexes cis-Pt^II(R⁶NH₂)(NH₃)X₂ and cis-Pt^II(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[Pt^II(NH³)Cl₂I] generated in situ (for X₂ = CII) or by replacement of the iodo-chloro ligands in cis-Pt^II(RNH₂)(NH₃)CII by dichloro and oxalato ligands. The complexes obtained were characterized by elemental analysis and by IR, UV, and ESR spectra. For cis-Pt^II(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.