We report on the preparation and thorough characterization of cytotoxic half-sandwich complexes [Ru(η⁶-pcym)(bphen)(dca)]PF₆ (Ru-dca) and [Os(η⁶-pcym)(bphen)(dca)]PF₆ (Os-dca) containing dichloroacetate(1-) (dca) as the releasable O-donor ligand bearing its own cytotoxicity; pcym = 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 (IC50 = 3.5 μM for Ru-dca, and 2.6 μM for Os-dca) against the A2780 human ovarian carcinoma cells than cisplatin (IC50 = 5.9 μM), while their toxicity on the healthy human hepatocytes was found to be IC50 = 19.1 μM for Ru-dca and IC50 = 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.

• Keywords
• cytotoxicity, dichloroacetate(1–), flow cytometry, half-sandwich, osmium, ruthenium,
• MeSH
• Phenanthrolines chemistry   pharmacology   MeSH
• Coordination Complexes chemistry   pharmacology   MeSH
• Dichloroacetic Acid chemistry   pharmacology   MeSH
• Humans MeSH
• Ligands MeSH
• Ovarian Neoplasms drug therapy   MeSH
• Osmium chemistry   MeSH
• Cell Proliferation drug effects   MeSH
• Ruthenium chemistry   MeSH
• Drug Liberation MeSH
• Check Tag
• Humans MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• bathophenanthroline MeSH Browser
• Phenanthrolines MeSH
• Coordination Complexes MeSH
• Dichloroacetic Acid MeSH
• Ligands MeSH
• Osmium MeSH
• Ruthenium MeSH

Halogenido and carboxylato Ru(II) half-sandwich complexes of the general composition [Ru(η⁶-p-cym)(dpa)X]PF₆ (1-5) were prepared and thoroughly characterized with various techniques (e.g., mass spectrometry, NMR spectroscopy and X-ray analysis); dpa = 2,2'-dipyridylamine; p-cym = p-cymene; X = Cl- (for 1), Br- (for 2), I- (for 3), valproate(1-) (for 4) or 4-phenylbutyrate(1-) (for 5). A single-crystal X-ray analysis showed a pseudo-octahedral piano-stool geometry of [Ru(η⁶-p-cym)(dpa)I]PF₆ (3), with a η⁶-coordinated p-cymene, bidentate N-donor dpa ligand and iodido ligand coordinated to the Ru(II) atom. The results of the ¹H-NMR solution behaviour studies proved that the complexes 1-5 hydrolyse were in the mixture of solvents used (10% MeOD-d₄/90% D₂O). Complexes 1-5 were in vitro inactive against the A2780 human ovarian carcinoma cell line, up to the highest tested concentration (IC50 > 100 μM).

• Keywords
• 2,2′-dipyridylamine, X-ray structure, half-sandwich, in vitro cytotoxicity, ruthenium, solution behaviour,
• MeSH
• Glutathione chemistry   MeSH
• Crystallography, X-Ray MeSH
• Humans MeSH
• Models, Molecular MeSH
• Molecular Structure MeSH
• Cell Line, Tumor MeSH
• Neoplasms drug therapy   MeSH
• Antineoplastic Agents chemical synthesis   chemistry   MeSH
• Proton Magnetic Resonance Spectroscopy MeSH
• Drug Design * MeSH
• Solvents chemical synthesis   chemistry   MeSH
• Ruthenium chemistry   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Glutathione MeSH
• Antineoplastic Agents MeSH
• Solvents MeSH
• Ruthenium MeSH