A series of organoruthenium(II) chlorido complexes with fluorinated O,O-ligands [(η(6)-p-cymene)Ru(F3C-acac-Ar)Cl] (1a-6a) and their respective 1,3,5-triaza-7-phosphaadamantane (pta) derivatives [(η(6)-p-cymene)Ru(F3C-acac-Ar)pta]PF6 (1b-6b) were synthesized and fully characterized in both solution and solid state. All complexes were inactive against nonmalignant keratinocytes but displayed variable activity against cancer cell models (ovarian, osteosarcoma). Compounds with a ligand containing the 4-chlorophenyl substituent (6a and 6b) exhibited the strongest anticancer effects. Despite a marginally lower cellular Ru accumulation compared to the chlorido complexes, pta analogues showed higher activity especially in the osteosarcoma model. Reduction of glutathione levels by buthionine sulfoximine (BSO) significantly enhanced the activity of all compounds with the most pronounced effects being observed for the pta series resulting in IC50 values down to the nanomolar range. While all chlorido complexes potently induce reactive oxygen species, DNA damage, and apoptosis, the respective pta compounds widely lacked ROS production but blocked cell cycle progression in G0/G1 phase.

Five different fluorinated β-diketone ligands in the presence of sodium methoxide easily react with the organoruthenium precursor [(η 6 -p-cymene)Ru(μ-Cl)Cl] 2 , generating neutral complexes 1−5 with typical "piano-stool" geometry. All synthesized compounds were characterized by multinuclear NMR, X-ray diffraction, and other standard physicochemical methods. These isolated organoruthenium-(II) complexes are air-, moisture-, and UV-stable compounds and were tested for catalytic activity. It was found that these compounds are ready to use catalysts, which are efficient for direct arylation of 2-phenylpyridine. With the use of 4bromoacetophenone as arylating reagent, these complexes show enhanced selectivity for monoarylated products. All reagents are commercially available and relatively inexpensive, which makes these catalysts generally available.

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Two acetazolamide (AAZ) complexes with ruthenium(II) η6-p-cymene chloride were synthesised, characterised and tested for their inhibitory effects on several carbonic anhydrase (CA, EC 4.2.1.1) isoforms with pharmacological applications. Against human (h) isoform hCA I, the two complexes showed inhibition constants in the range of 8.5–23.4 nM (AAZ has a KI of 250 nM), against hCA II of 0.48–4.2 nM, whereas against hCA IX of 0.63–3.8 nM and against hCA XII of 0.04–0.52 nM, respectively. These highly effective ruthenium acetazolamide derivatives against the tumour-associated CA isoforms IX and XII warrant further in vivo studies, in hypoxic tumours overexpressing these enzymes.

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