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

Agnieszka Gilewska,Joanna Masternak,Eliza Turlej,Barbara Barszcz,Joanna Wietrzyk,Jerzy Sitkowski,Katarzyna Kazimierczuk

doi:10.1007/s00775-019-01665-2

Abstract

In this paper, we discussed the similarities and differences in d6 low-spin half-sandwich ruthenium, rhodium and iridium complexes containing 2,2′-biimidazole (H2biim). Three new complexes, {[RuCl(H2biim)(η6-p-cymene)]PF6}2·H2O (1), [(η5-Cp)RhCl(H2biim)]PF6 (2), and [(η5-Cp)IrCl(H2biim)]PF6 (3), were fully characterized by CHN, X-ray diffraction analysis, UV–Vis, FTIR, and 1H, 13C and 15N 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 IC50 value of 2.20 µg. Importantly, 1 displayed the highest activity against HL-60 (IC50 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.

Highlights

By screening the literature connected to the effort of scientists attempting to resolve the problems associated with cancer treatment, it should be noted that organometallic, bioinorganic and bioorganic chemistry are important branches of this subject
The main purposes of the present work were as follows: (1) synthesis and full physicochemical characterization of d 6 low-spin arene ruthenium and isostructural pentamethylcyclopentadienyl rhodium and iridium half-sandwich complexes with 2,2′-biimidazole, (2) determination and comparison of lipophilicity and in vitro cytotoxic properties, and (3) investigation of the types of interactions with biological targets (DNA, human serum albumin (HSA), and GSH)
The reaction of appropriate metal precursors: dichloro(pcymene)ruthenium(II) dimer [(η6-p-cymene)Ru(μ-Cl) Cl]2, pentamethylcyclopentadienylrhodium(III) dimer [CpRh(μ-Cl)Cl]2, pentamethylcyclopentadienyliridium (III) dimer [CpIr(μ-Cl)Cl]2, with 2,2-biimidazole ligand (H2biim) with appropriate ratio in dry mixture of methanol/dichloromethane resulted in the formation of d6 lowspin half-sandwich ruthenium, rhodium and iridium complexes: {[RuCl(H2biim)(η6-p-cymene)]PF6}2·H2O (1), [(η5-Cp)RhCl(H2biim)]PF6 (2) and [(η5-Cp)IrCl(H2biim)] PF6 (3) (Fig. 1)

Summary

Introduction

By screening the literature connected to the effort of scientists attempting to resolve the problems associated with cancer treatment, it should be noted that organometallic, bioinorganic and bioorganic chemistry are important branches of this subject. We attempted to estimate whether the presence of hydrogen bonds and noncovalent interactions (HS analysis) influenced the stability and cytotoxic activity of the obtained complexes. The main purposes of the present work were as follows: (1) synthesis and full physicochemical characterization of d 6 low-spin arene ruthenium and isostructural pentamethylcyclopentadienyl rhodium and iridium half-sandwich complexes with 2,2′-biimidazole, (2) determination and comparison of lipophilicity and in vitro cytotoxic properties, and (3) investigation of the types of interactions with biological targets (DNA, HSA, and GSH).

Results

Conclusion