FULL PAPER DOI:10.1002/ejic.201402754 Monothiolato-Bridged Dinuclear Arene Ruthenium Complexes: The Missing Link in the Reaction of Arene Ruthenium Dichloride Dimers with Thiols David Stíbal, [a] Bruno Therrien, [a] Federico Giannini, [b] Lydia E. H. Paul, [b] Julien Furrer, [b] and Georg Süss-Fink* [a] Dedicated to Professor Klaus Bernauer on the occasion of his 80th birthday Keywords: Ruthenium / Dinuclear complexes / Arene ligands / Bridging ligands / Cytotoxicity The monothiolato complexes [(η 6 -p-MeC 6 H 4 iPr) 2 Ru 2 Cl 2 - (μ-Cl)(μ-SR)] with R = CH 2 C 6 H 5 (1), p-CH 2 C 6 H 4 NO 2 (2), C 10 H 15 (3), m-9-B 10 C 2 H 11 (4) were synthesized by treating [(η 6 -p-MeC 6 H 4 iPr) 2 Ru 2 Cl 2 (μ-Cl) 2 ] with the corresponding thiols RSH. The reaction of p-cymene ruthenium dichloride dimer with thiols is well known to give the cationic trithiolato complexes [(η 6 -p-MeC 6 H 4 iPr) 2 Ru 2 (μ-SR) 3 ] + , but recently the intermediary dithiolato complexes [(η 6 -p-MeC 6 H 4 iPr) 2 - Introduction Discovered in 1844 by Karl Ernst Claus, ruthenium was for more than a century of almost no practical use and had hardly found interest in chemical research prior to 1980. However, today ruthenium is one of the best-studied and most exciting transition metals, thanks to its outstanding catalytic, light-harvesting, and biological properties. [1] Thus, ruthenium complexes have found applications as catalysts for a variety of organic transformations, such as enantiose- lective hydrogenations and olefin metathesis reactions, [2] for dye-sensitized solar cells, [3] and as anticancer drugs. [4] In particular, the chemistry of arene ruthenium com- plexes has found a steadily growing interest, [5] ever since Winkaus and Singer reported in 1967 the synthesis of [(η 6 - C 6 H 6 ) 2 Ru 2 Cl 2 (μ-Cl) 2 ], which was at first considered to be a polymer, [6] but shown later to be a dimer. [7,8] Thus, the di- meric arene ruthenium dichloride complexes were found to react with thiols to give cationic trithiolato complexes of the type [(η 6 -arene) 2 Ru 2 (μ-SR) 3 ] + , the first examples being the hexamethylbenzene derivative [(η 6 -C 6 Me 6 ) 2 Ru(μ- SC 6 H 5 ) 3 ] + reported by Schacht et al., [9] and the p-cymene derivative [(η 6 -p-MeC 6 H 4 iPr) 2 Ru(μ-SC 6 H 5 ) 3 ] + , reported by [a] Institut de Chimie, Université de Neuchâtel, Avenue de Bellevaux 51, 2000 Neuchâtel, Switzerland E-mail: georg.suess-fink@unine.ch http://www2.unine.ch/chs/page-10195.html [b] Department für Chemie und Biochemie, Universität Bern Freiestrasse 3, CH-3012 Bern, Switzerland Eur. J. Inorg. Chem. 2014, 5925–5931 © 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 5925 Ru 2 Cl 2 (μ-SR) 2 ] could also be isolated and characterized in some cases. The monothiolato complexes 1–4 now observed represent the missing link in the stepwise formation of the trithiolato complexes. The single-crystal X-ray structure analyses of complexes 1 and 2 show the two ruthenium atoms to be bridged by a chlorido ligand and by the thiolato ligand without a metal–metal bond, which is in accordance with the eighteen-electron rule. Mashima et al., [10] both containing three thiophenolato bridges. We completed this series in 2003 by the p-bromo- thiophenolato derivative [(η 6 -p-MeC 6 H 4 iPr) 2 Ru 2 (μ-S-p- C 6 H 4 Br) 3 ] + , [11] the p-methylthiophenolato and p-hydroxy- thiophenolato derivatives [(η 6 -arene) 2 Ru 2 (μ-S-p-C 6 H 4 X) 3 ] + (arene = C 6 H 6 , p-MeC 6 H 4 iPr, C 6 Me 6 ; X = CH 3 , OH), [12] as well as the 2-hydroxyethylthiolato derivatives [(η 6 -arene) 2 - Ru 2 (μ-SCH 2 CH 2 OH) 3 ] + (arene = C 6 H 6 , p-MeC 6 H 4 iPr, C 6 Me 6 ). [12] We also found that the chloride salts of the tri- thiolato complexes [(η 6 -arene) 2 Ru 2 (μ-SR) 3 ] + are highly cytotoxic for human ovarian cancer cells; [13] they are in fact among the most active ruthenium anticancer compounds. [4] The IC 50 values of these compounds are in the nanomolar range for A2780 human ovarian cancer cells and for their cisplatin-resistant mutant A2780cisR. [14–16] We could show that these complexes, the most active derivative being [(η 6 - p-MeC 6 H 4 iPr) 2 Ru 2 (μ-S-p-C 6 H 4 tBu) 3 ] + (IC 50 30 nM for both A2780 and A2780cisR cell lines), [14] are highly ef- ficient catalysts for the oxidation of glutathione with air in aqueous solution, which may at least partly explain their high cytotoxicity. [17] We recently observed that the synthesis of the trithiolato complexes [(η 6 -arene) 2 Ru 2 (μ-SR) 3 ] + proceeds through the intermediacy of the dithiolato complexes [(η 6 -arene) 2 Ru 2 - Cl 2 (μ-SR) 2 ], several representatives of which could be iso- lated and structurally characterized in the case of aliphatic thiolato ligands (Scheme 1). [18] Although monothiolato complexes are also expected as intermediates, they have