Similarities and differences in d6 low-spin ruthenium, rhodium and iridium half-sandwich complexes: synthesis, structure, cytotoxicity and interaction with biological targets

Abstract

In this paper, we discussed the similarities and differences in d 6 low-spin half-sandwich ruthenium, rhodium and iridium complexes containing 2,2′-biimidazole (H 2 biim). Three new complexes, {[RuCl(H 2 biim)(η 6 - p -cymene)]PF 6 } 2 ·H 2 O ( 1 ), [(η 5 -Cp)RhCl(H 2 biim)]PF 6 ( 2 ), and [(η 5 -Cp)IrCl(H 2 biim)]PF 6 ( 3 ), were fully characterized by CHN, X-ray diffraction analysis, UV–Vis, FTIR, and 1 H, 13 C and 15 N NMR spectroscopies. The complexes exhibit a typical pseudooctahedral piano-stool geometry, in which the aromatic arene ring ( p -cymene or Cp) forms the seat, while the bidentate 2,2′-biimidazole and chloride ion form the three legs of the piano stool. Moreover, the cytotoxic activities of the compounds were examined in the LoVo, HL-60, MV-4-11, MCF-7 human cancer cell lines and BALB/3T3 normal mouse fibroblasts. Notably, the investigated complexes showed no cytotoxic effects towards the normal BALB/3T3 cell line compared to cisplatin, which has an IC 50 value of 2.20 µg. Importantly, 1 displayed the highest activity against HL-60 (IC 50 4.35 µg). To predict a binding mode, we explored the potential interactions of the metal complexes with CT-DNA and protein using UV absorption and circular dichroism. The obtained data suggest that the complexes could interact with CT-DNA via an outside binding mode. Moreover, binding of the complexes with the GSH via UV–Vis and ESI mass spectra was determined. Comparative studies have shown that the rhodium complex ( 2 ) is the most GSH reactive, which is probably responsible for its deactivation towards LoVo and MCF-7 tumour cells. The influence of the metal ion on the biological activity of isostructural Rh(III) and Ir(III) complexes was an important goal of the presented investigation. Electronic supplementary material The online version of this article (10.1007/s00775-019-01665-2) contains supplementary material, which is available to authorized users.

Ligand‐Controlled Reactivity and Cytotoxicity of Cyclometalated Rhodium(III) Complexes

“…Nevertheless, research on cyclometalated rhodium complexes has largely focused on non‐cyclopentadienyl cyclometalated rhodium complexes that target DNA, enzyme or protein–protein interfaces , , . Reported cyclopentadienyl rhodium anticancer complexes to date, have mainly contained N ^ N,, N ^ S, N ^ O, or O ^ O, , chelating ligands.…”

Ruthenium(II) and Iridium(III) Complexes as Tested Materials for New Anticancer Agents

“…To see if the presence of GSH significantly reduces the cytotoxic activity of the complexes, glutathione deactivation experiments were carried out using the Ellman method [ 21 , 29 ]. The results given as the concentration of unreacted GSH remaining after 28 h incubation with the iridium(III) complexes show that both iridium(III) complexes 2 and 3 had the same results (0.037 mmol/L).…”

“…The cytotoxicity of the investigated complexes 1-3 was determined by microculture with sulforhodamine B SRB (all adherent cells) and MTT ([3-(4,5-dimethyl(thiazol-2-yl) -2,5-diphenyltetrazoliumbromide)]) (for cells in suspension (leukemia cells)) assays with the following three tumor cell lines: colorectal adenoma (LoVo), myelomonocytic leukemia (MV-4-11), and breast adenocarcinoma (MCF-7), as well as a healthy mouse fibroblast (BALB/3T3) cell line. The cytotoxicity of the compounds was measured using the methods described previously [21]. The in vitro cytotoxic activity results were presented as the percentage of inhibition of cell proliferation by the tested compounds or DMSO, which was used as a solvent (at a concentration of 10 µg/mL of the tested compound was 0.1% DMSO).…”

“…Determination of log P values, and studies on the interactions of ruthenium(II) (1), iridium(III) complexes (2, 3) with CT-DNA, HSA and GSH, were performed according to the previous procedure published in the paper [21].…”

“…It is commonly believed that the main target for antitumor metal complexes is DNA, as has been shown for platinum/ruthenium drugs [30]. In terms of the antitumor activity of iridium To see if the presence of GSH significantly reduces the cytotoxic activity of the complexes, glutathione deactivation experiments were carried out using the Ellman method [21,29]. The results given as the concentration of unreacted GSH remaining after 28 h incubation with the iridium(III) complexes show that both iridium(III) complexes 2 and 3 had the same results (0.037 mmol/L).…”