Multinuclear magnetic resonance studies of the hydrolyzed and aquated species of the antitumor complexes cis-Pt(cyclobutylamine) 2X 2 and cis-Pt(NH 3)(cyclobutylamine)X 2 and antitumor testing of mixed -amine Pt(II) compounds

Abstract

The aquated and hydrolyzed species formed from the complexes cis-Pt(cba) 2I 2 and cis-Pt(NH 3)(cba)I 2 (cba = cyclobutylamine) were studied by multinuclear ( 195Pt, 15N and 1H) magnetic resonance spectroscopy. The iodo ligands were removed with AgNO 3. 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(NH 3) 2 system, probably due to the greater lipophilicity of cba compared to NH 3. 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(NH 3)(cba)Cl 2 are also included.