Thiophenolato-bridged dinuclear areneruthenium complexes: a new family of highly cytotoxic anticancer agents

Abstract

New cationic diruthenium complexes of the type [(arene)₂Ru₂(SPh)₃]⁺, arene being C₆H₆, p-ⁱPrC₆H₄Me, C₆Me₆, C₆H₅R, where R = (CH₂)_nOC(O)C₆H₄-p-O(CH₂)₆CH₃ or (CH₂)_nOC(O)CHCHC₆H₄-p-OCH₃ and n = 2 or 4, are obtained from the reaction of the corresponding precursor [(arene)RuCl₂]₂ and thiophenol and isolated as their chloride salts. The complexes have been fully characterised by spectroscopic methods and the solid state structure of [(C₆H₆)₂Ru₂(SPh)₃]⁺, crystallised as the hexafluorophosphate salt, has been established by single crystal X-ray diffraction. The complexes are highly cytotoxic against human ovarian cancer cells (cell lines A2780 and A2780cisR), with the IC₅₀ values being in the submicromolar range. In comparison the analogous trishydroxythiophenolato compounds [(arene)₂Ru₂(S-p-C₆H₄OH)₃]Cl (IC₅₀ values around 100 μM) are much less cytotoxic. Thus, it would appear that the increased antiproliferative effect of the arene ruthenium complexes is due to the presence of the phenyl or toluyl substituents at the three thiolato bridges.