Thiolato‐Bridged Arene–Ruthenium Complexes: Synthesis, Molecular Structure, Reactivity, and Anticancer Activity of the Dinuclear Complexes [(arene)₂Ru₂(SR)₂Cl₂]

Abstract

Keywords: Ruthenium / Arene ligands / Thiolato bridges / CytotoxicityTreatment of an arene-ruthenium dichloride dimer with thiols RSH to lead to cationic trithiolato complexes of the type [(arene) 2 Ru 2 (SR) 3 ] + was shown to proceed through the neutral thiolato complexes [(arene) 2 Ru 2 (SR) 2 Cl 2 ], which have been isolated and characterized for arene = p-MeC 6 H 4 iPr and R = CH 2 Ph (1), CH 2 CH 2 Ph (2), CH 2 C 6 H 4 -p-tBu (3), and C 6 H 11 (4). The single-crystal X-ray structure analysis of the p-tert-butylbenzyl derivative 3 reveals that the two ruthe-

Synthesis, Characterisation and In Vitro Anticancer Activity of Hexanuclear Thiolato‐Bridged Arene Ruthenium Metalla‐Prisms

“…This does not appear to influence the SRu distances but slightly decreases the dative bond length to the aromatic ring (2.296 vs. 2.308 Å for the complexes), which may contribute to the stability of 2 a compared with 5 . Overall, the DFT calculation supports our findings and, considering the fact that complex 2 a is only obtained at low temperature and under strict stoichiometry,10 it is not surprising that complex 5 has remained undetected and that the formation of the metalla‐prisms were obtained from 2 .…”

“…Our first attempt involved use of the known chloro‐bridged metalla‐prism [( p ‐cymene) 6 Ru 6 Cl 6 (tpt) 2 ] 6+ as the starting material 11. In analogy to the preparation of the dithiolato‐bridged dinuclear arene ruthenium complexes 2 a – c , which involved addition of RSH to the dinuclear chloro‐bridged complex [( p ‐cymene) 2 Ru 2 Cl 4 ] at low temperature,10 an excess of RSH was added to [( p ‐cymene) 6 Ru 6 Cl 6 (tpt) 2 ](CF 3 SO 3 ) 6 in ethanol at 0 °C (Scheme S1). Unfortunately, only mixtures of compounds that we were unable to separate were obtained.…”

“…Instead, it was found that addition of silver triflate to the dithiolato‐bridged dinuclear complexes [( p ‐cymene) 2 Ru 2 (SR) 2 Cl 2 ] ( 2 ),10 followed by addition of tpt in ethanol, afforded the desired metalla‐prisms after moderate heating for several hours (Scheme ). The hexacationic metalla‐prisms [( p ‐cymene) 6 Ru 6 (SR) 6 (tpt) 2 ] 6+ ( 3 a – c ) were isolated as the triflate salts.…”

“…The dinuclear complexes 1 a – c , bridged by three thiolato ligands and isolated as their chloride salts, appear to be among the most active arene ruthenium complexes evaluated so far. Interestingly, the neutral dinuclear dithiolato arene ruthenium precursors [( p ‐cymene) 2 Ru 2 (SR) 2 Cl 2 ] (R=CH 2 Ph ( 2 a ), CH 2 C 6 H 4 ‐ p ‐ t Bu ( 2 b ), CH 2 CH 2 Ph ( 2 c )) are significantly less cytotoxic,10 despite sharing similar structural features (Figure 1).…”

Encapsulation of the Dinuclear Trithiolato‐Bridged Arene Ruthenium Complex Diruthenium‐1 in an Apoferritin Nanocage: Structure and Cytotoxicity

“…The most active member of this family is [(η 6 ‐ p ‐Me‐C 6 H 4 i Pr) 2 Ru 2 (μ 2 ‐S‐ p ‐C 6 H 4 t Bu) 3 ]Cl, termed diruthenium‐1 or DiRu‐1 (Figure ) . This compound is very toxic in vitro toward hepatocellular carcinoma (HepG2 cells), estrogen‐responsive breast adenocarcinoma (MCF‐7 cells) and BT549 cells, triple‐negative breast adenocarcinoma (MDA‐MB‐231 cells), human ovarian cancer (A2780 cells), and the cisplatin‐resistant cell line A2780cis, with IC 50 values in the low nanomolar range . Recent in vivo studies, have demonstrated that these complexes have potential as anticancer drugs, especially DiRu‐1, which significantly prolongs the survival of tumor‐bearing mice .…”