Synthesis, Molecular Structure and Cytotoxicity of Molecular Materials Based on Water Soluble Half-Sandwich Rh(III) and Ir(III) Tetranuclear Metalla-Cycles.

Gajendra Gupta,Bruno Therrien,Paul Dyson,Benjamin Murray

doi:10.3390/ma6115352

Abstract

The neutral dinuclear complexes [(η5-C5Me5)2Rh2(μ-dhnq)Cl2] (1) and [(η5-C5Me5)2Ir2(μ-dhnq)Cl2] (2) (dhnqH2 = 5,8-dihydroxy-1,4-naphthoquinone) were obtained from the reaction of [(η5-C5Me5)M(μ-Cl)Cl]2 (M = Rh, Ir) with dhnqH2 in the presence of CH3COONa. Treatment of 1 or 2 in methanol with linear ditopic ligands L (L = pyrazine, 4,4′-bipyridine or 1,2-bis(4-pyridyl)ethylene), in the presence of AgCF3SO3, affords the corresponding tetranuclear metalla-rectangles [(η5-C5Me5)4M4(μ-dhnq)2(μ-L)2]4+ (L = pyrazine, M = Rh, 3; M = Ir, 4; L = 4,4′-bipyridine, M = Rh, 5; M = Ir, 6; L = 1,2-bis(4-pyridyl)ethylene, M = Rh, 7; M = Ir, 8). All complexes were isolated as their triflate salts and were fully characterized by infrared, 1H and 13C NMR spectroscopy, and some representative complexes by single-crystal X-ray structure analysis. The X-ray structures of 3, 5 and 6 confirm the formation of the tetranuclear metalla-cycles, and suggest that complexes 5 and 6 possess a cavity of sufficient size to encapsulate small guest molecules. In addition, the antiproliferative activity of the metalla-cycles 3–8 was evaluated against the human ovarian A2780 (cisplatin sensitive) and A2780cisR (cisplatin resistant) cancer cell lines and on non-tumorigenic human embryonic kidney HEK293 cells. All cationic tetranuclear metalla-rectangles were found to be highly cytotoxic, with IC50 values in the low micromolar range.

Highlights

The biological application of coordination-driven arene ruthenium metalla-materials is a flourishing area of research [1,2,3,4,5,6]
Following the promising studies of arene ruthenium metalla-materials, a series of cationic arene osmium metalla-rectangles were recently reported [21]. These arene osmium derivatives display comparable cytotoxicity to the ruthenium-based analogues, suggesting that the biological applications of arene ruthenium metalla-rectangles can be extended to other transition metals
The reaction of the dinuclear pentamethylcyclopentadienyl complexes [(η5-C5Me5)M(μ-Cl)Cl]2 (M = Rh and Ir) with dhnqH2 in methanol in the presence of CH3COONa leads to the formation of the neutral complexes [(η5-C5Me5)2Rh2(μ-dhnq)Cl2]

Summary

Introduction

The biological application of coordination-driven arene ruthenium metalla-materials is a flourishing area of research [1,2,3,4,5,6]. The tetranuclear assemblies have been found to possess good anticancer activity [7,8,9,10,11,12], to strongly interact with DNA [13,14], and to efficiently detect biologically relevant analytes [15,16,17] Their DNA binding can occur through non-covalent interactions, novel modes of action observed for di- and trinuclear organometallics [18,19,20], fragmentation inside cells followed by coordination of the metal ion to DNA and/or other biomolecules cannot be excluded. Following the promising studies of arene ruthenium metalla-materials, a series of cationic arene osmium metalla-rectangles were recently reported [21]. The anticancer activity of these pentamethylcyclopentadienyl rhodium and iridium metalla-rectangles was compared to that of [(η6-p-PriC6H4Me)4Ru4(μ-dhnq)2(μ-4,4′-bipyridine)2](CF3SO3) (Figure 1) [9]

Results and Discussion

Antiproliferative Activity

General

3.10. Cell Culture and Inhibition of Cell Growth

3.11. Single-Crystal X-ray Structure Analysis

Conclusions