Synthesis, molecular structure, computational study and in vitro anticancer activity of dinuclear thiolato-bridged pentamethylcyclopentadienyl Rh(iii) and Ir(iii) complexes

Abstract

Neutral dinuclear dithiolato-bridged pentamethylcyclopentadienyl Rh(III) complexes of the type (C₅Me₅)₂Rh₂(μ-SR)₂Cl₂ (R = CH₂Ph, 1; R = CH₂CH₂Ph, 2) and cationic dinuclear trithiolato-bridged pentamethylcyclopentadienyl Rh(III) and Ir(III) complexes of the type [(C₅Me₅)₂M₂(μ-SR)₃]⁺ (M = Rh, R = CH₂Ph, 3; M = Rh, R = CH₂CH₂Ph, 5; M = Rh, R = CH₂C₆H₄-p-^tBu, 7: M = Ir, R = CH₂Ph, 4; M = Ir, R = CH₂CH₂Ph, 6; M = Ir, R = CH₂C₆H₄-p-^tBu, 8) have been synthesized from the chloro-bridged pentamethylcyclopentadienyl Rh(III) and Ir(III) dimers (C₅Me₅)₂M₂(μ-Cl)₂Cl₂ by reaction with the corresponding thiol derivative (RSH). Complexes 3–8 were isolated as chloride salts. All complexes were obtained in good yield and were fully characterized by spectroscopic methods. The molecular structures of the neutral complexes (1 and 2) show interesting features: the two rhodium atoms are bridged by two thiolato ligands with no metal–metal bonds and the pentamethylcyclopentadienyl and chlorido ligands are oriented syn to each other, an uncommon conformation for such dinuclear complexes. These structural features were rationalized using DFT calculations. Additionally, the antiproliferative activity of the complexes was evaluated against the cancerous A2780 (cisplatin sensitive) and A2780cisR (cisplatin resistant) human ovarian cell lines and on the noncancerous HEK293 human embryonic kidney cells. All complexes were found to be active and the cationic iridium complexes 4, 6 and 8 are particularly cytotoxic, with IC₅₀ values in the nanomolar range (IC₅₀ < 0.1 μM). The catalytic activity of the complexes for the oxidation of glutathione (GSH) to GSSG was evaluated by NMR spectroscopy.