Osmium NAMI-A analogues:: Synthesis, structural and spectroscopic characterization, and antiproliferative properties

The osmium(III) complex [(DMSO)(2)H][trans-(OsCl4)-Cl-III(DMSO)(2)] (1) has been prepared via stepwise reduction of OsO4 in concentrated HCl using N2H4 center dot 2HCl and SnCl2 center dot 2H(2)O in DMSO. 1 reacts with a number of azole ligands, namely, indazole (Hind), pyrazole (Hpz), benzimidazole (Hbzim), imidazole (Him), and 1H-1,2,4-triazole (Htrz), in organic solvents, affording novel complexes (H(2)ind)[(OsCl4)-Cl-III(Hind)(DMSO)] (2), (H(2)pz)[(OsCl4)-Cl-III(Hpz)(DMSO)] (3), (H(2)bzim)[(OsCl4)-Cl-III(Hbzim)(DMSO)] (4), (H(2)im)[(OsCl4)-Cl-III(Him)(DMSO)] (6), and (H(2)trz)[(OsCl4)-Cl-III(Htrz)(DMSO)] (7), which are close analogues of the antimetastatic complex NAMI-A. Metathesis reaction of 4 with benzyltriphenylphosphonium chloride in methanol led to the formation of (Ph3PCH2Ph)[(OsCl4)-Cl-III(Hbzim)(DMSO)] (5). The complexes were characterized by IR, UV-vis, ESI mass spectrometry, H-1 NMR spectroscopy, cyclic voltammetry, and X-ray crystallography. In contrast to NAMI-A, 2-4, 6, and 7 are kinetically stable in aqueous solution and resistant to hydrolysis. Surprisingly, they show reasonable antiproliferative activity in vitro in two human cell lines, HT-29 (colon carcinoma) and SK-BR-3 (mammary carcinoma), when compared with analogous ruthenium compounds. Structure-activity relationships and the potential of the prepared complexes for further development are discussed.