Multinuclear magnetic resonance studies of the hydrolyzed and aquated species of the antitumor complexes cis-Pt(cyclobutylamine)2X2 and cis-Pt(NH3)(cyclobutylamine)X2 and antitumor testing of mixed-amine Pt(II) compounds

The aquated and hydrolyzed species formed from the complexes cis-Pt(cba)2I2 and cis-Pt(NH3)(cba)I2 (cba = cyclobutylamine) were studied by multinuclear (195Pt, 15N and 1H) magnetic resonance spectroscopy. The iodo ligands were removed with AgNO3. In acidic medium, the aqueous product consists of the diaqua and the aqua-nitrato cations, although some monohydroxo-bridged dimers are formed after several hours, especially for the mixed-ligand compound. In basic medium, the main species are the dihydroxo compounds. At neutral pD, several species exist in solution, especially with the mixed-amine system, which contained also a small quantity of the symmetric cis-Pt(cba)2 complexes. Difficulties were encountered because of the insolubility of several oligomeric species, contrary to the cis-Pt(NH3)2 system, probably due to the greater lipophilicity of cba compared to NH3. Monohydroxo-bridged dimers are formed in large quantities and the stereochemistry of the mixed-amine species was determined by 15N NMR spectroscopy. For the latter system, the cyclic dihydroxo-bridged dimers are the predominant species at neutral pD after a few hours. After an extended period of time, most of the oligomers precipitate, leaving the more soluble monohydroxo-bridged dimers as the major species in solution. The preliminary antitumor testing results on several dichloro mixed-ligand compounds are listed. The results on further testing on the most active compound cis-Pt(NH3)(cba)Cl2 are also included.