Half-Sandwich Ru(II) and Os(II) Bathophenanthroline Complexes Containing a Releasable Dichloroacetato Ligand.

We report on the preparation and thorough characterization of cytotoxic half-sandwich complexes [Ru(η⁶- p cym)(bphen)(dca)]PF₆ ( Ru - dca ) and [Os(η⁶- p cym)(bphen)(dca)]PF₆ ( Os - dca ) containing dichloroacetate(1-) (dca) as the releasable O -donor ligand bearing its own cytotoxicity; p cym = 1-methyl-4-(propan-2-yl)benzene ( p -cymene), bphen = 4,7-diphenyl-1,10-phenanthroline (bathophenanthroline). Complexes Ru - dca and Os-dca hydrolyzed in the water-containing media, which led to the dca ligand release (supported by ¹H NMR and electrospray ionization mass spectra). Mass spectrometry studies revealed that complexes Ru- dca and Os-dca do not interact covalently with the model proteins cytochrome c and lysozyme. Both complexes exhibited slightly higher in vitro cytotoxicity (IC ₅₀ = 3.5 μM for Ru- dca , and 2.6 μM for Os-dca ) against the A2780 human ovarian carcinoma cells than cisplatin (IC ₅₀ = 5.9 μM), while their toxicity on the healthy human hepatocytes was found to be IC ₅₀ = 19.1 μM for Ru- dca and IC ₅₀ = 19.7 μM for Os-dca . Despite comparable cytotoxicity of complexes Ru- dca and Os-dca , both the complexes modified the cell cycle, mitochondrial membrane potential, and mitochondrial cytochrome c release by a different way, as revealed by flow cytometry experiments. The obtained results point out the different mechanisms of action between the complexes.
Competing Interests: The authors declare no conflict of interest.