SYNTHESIS AND ANTITUMOR-ACTIVITY OF AMMINE AMINE PLATINUM(II) AND PLATINUM(IV) COMPLEXES

Dimeric platinum complexes, [Pt(RNH2)I2]2 (Where R = H, methyl, ethyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl), hav e been synthesized by reactions of diiodoplatinum compounds with perch loric acid in water/ethanol solutions. The dimerization varies from se veral hours to a few days depending upon the length of the carbon chai n in the alkylamines and the process can be conveniently monitored by Pt-195 NMR spectroscopy. All these dimers exhibit two closely separate d resonances around -4000 ppm (vs K2PtCl4 at -1620 ppm) in dimethylfor mamide. Reactions of [Pt(NH3)I2]2 with alkylamines do not yield the de sired mixed ammine/amine complexes, which are obtained subsequently by treatment of the alkylamine dimer [Pt(RNH2)I2]2 with ammonium hydroxi de in water. By using this latter procedure, a novel class of ammine/a mine platinum complexes of the type PtII(NH3)(RNH2)Cl2, PtIV(NH3)(RNH2 )X2A2, and PtIV(NH3)(RNH2)(CBDCA)A2 . H2O, where X2 = chloro or 1,1-cy clobutanedicarboxylato (CBDCA), A = OH, Cl, or OCOCH3, have been synth esized and characterized by elemental analysis, infrared, and Pt-195 N MR spectroscopic techniques. The alicyclic ammine/amine Pt(II) complex es, where R is C3-C6 were selected as representative of the class to u ndergo antitumor evaluations. The compounds had excellent activity aga inst murine leukemic L1210/0 cells with cyclobutylamine-, cyclopentyla mine- and cyclohexylamine-containing complexes demonstrating cytotoxic ity superior to that of the clinically established cisplatin.