Organometallic Osmium Arene Complexes with Potent Cancer Cell Cytotoxicity

Iodido osmium(II) complexes [Os(η⁶-arene)(XY)I]⁺ (XY = <i>p</i>-hydroxy or <i>p</i>-dimethylaminophenylazopyridine, arene = <i>p</i>-cymene or biphenyl) are potently cytotoxic at nanomolar concentrations toward a panel of human cancer cell lines; e.g., IC₅₀ = 140 nM for [Os(η⁶-bip)(azpy-NMe₂)I]⁺ toward A2780 ovarian cancer cells. They exhibit low toxicity and negligible deleterious effects in a colon cancer xenograft model, giving rise to the possibility of a broad therapeutic window. The most active complexes are stable and inert toward aquation. Their cytotoxic activity appears to involve redox mechanisms.