Osmium(III) Analogues of KP1019: Electrochemical and Chemical Synthesis, Spectroscopic Characterization, X‑ray Crystallography, Hydrolytic Stability, and Antiproliferative Activity

A one-electron reduction of osmium­(IV)
complexes trans-[OsIVCl4(Hazole)2], where Hazole = 1H-pyrazole ([1]0), 2H-indazole ([2]0), 1H-imidazole ([3]0), and 1H-benzimidazole ([4]0), afforded a series of eight new complexes as osmium analogues of
KP1019, a lead anticancer drug in clinical trials, with the general
formula (cation)­[trans-OsIIICl4(Hazole)2], where cation = H2pz+ (H2pz­[1]), H2ind+ (H2ind­[2]), H2im+ (H2im­[3]), Ph4P+ (Ph4P­[3]), nBu4N+ (nBu4N­[3]), H2bzim+ (H2bzim­[4]), Ph4P+ (Ph4P­[4]), and nBu4N+ (nBu4N­[4]). All complexes were characterized by elemental analysis, 1H NMR spectroscopy, electrospray ionization mass spectrometry,
UV–vis spectroscopy, cyclic voltammetry, while H2pz­[1], H2ind­[2], and nBu4[3], in addition, by X-ray diffraction.
The reduced species [1]− and [4]− are stable in aqueous media in the absence
of air oxygen and do not react with small biomolecules such as amino
acids and the nucleotide 5′-dGMP. Cell culture experiments
in five different human cancer cell lines (HeLa, A549, FemX, MDA-MB-453,
and LS-174) and one noncancerous cell line (MRC-5) were performed,
and the results were discussed and compared to those for KP1019 and
cisplatin. Benzannulation in complexes with similar structure enhances
antitumor activity by several orders of magnitude, implicating different
mechanisms of action of the tested compounds. In particular, complexes
H2ind­[2] and H2bzim­[4] exhibited significant antiproliferative activity in vitro when compared to H2pz­[1] and H2im­[3].