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)(2)I-2 and cis-Pt(NH3)(cba)I-2 (cba = cyclobutylamine) were studied by multinuclear (Pt-195, N-15 and H-1) 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 N-15 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)Cl-2 are also included. (c) 2008 Elsevier B.V. All rights reserved.