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

摘要

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 (~(195)Pt, ~(15)N and ~1H) magnetic resonance spectros_copy. 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 ~(15)N 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 majorspecies 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.