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-(t)Bu, 7: M = Ir, R = CH2Ph, 4; M = Ir, R = CH2CH2Ph, 6; M = Ir, R = CH2C6H4-p-(t)Bu, 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 , and 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.

Organometallic Iridium Arene Compounds: The Effects ofC-Donor Ligands on Anticancer Activity

“…The ligands surrounding the iridium metal ion play a large role in the compound's stability and may be of importance to the biological targeting. 22 There have been numerous reports of both iridium(I) and iridium(III) complexes containing N-, 2350 O-, 5161 P-6265 and Sdonor 6671 ligands, dimeric species, 33,72,73 mononuclear scaffolds 7479 and sandwich complexes, 8082 which have shown significant potential in the quest for new anticancer therapeutics. There have been several reviews on non-arene iridium complexes which incorporate a range of C-donor ligands, 19,83 however, due to the increased focus on iridium arene complexes over the past 5 years, this review will highlight this emerging research fields of cyclometalated and N-heterocyclic carbene iridium arene complexes as potential drug candidates.…”

Synthesis, structural, DFT calculations and biological studies of rhodium and iridium complexes containing azine Schiff-base ligands

“…Recently Therrien et.al reported dinuclear dithiolato bridged rhodium and iridium complexes which exhibit cytotoxicity against human ovarian cancer cells lines (A2780 and A2780cisR) [12]. C-H activated cyclometallated Rh(III) and Ir(III) complexes can effectively bind to DNA and protein through electrostatic and hydrophobic interactions [13].…”

Developments in Platinum-Group Metals as Dual Antibacterial and Anticancer Agents

“…e medical applications involve acting as anticancer and antimicrobial agents in the Rh(I), Rh(II), and Rh(III) states [25,[82][83][84][85][86][87][88][89][90][91][92][93][94]. Jeremić et al stated that Rh III complexes are isoelectronic with Rh II and Pt IV coordination compounds, which offer a variety of effective antitumour agents [83].…”