Cytotoxic dimeric half‐sandwich Ru(II), Os(II) and Ir(III) complexes containing the 4,4′‐biphenyl‐based bridging ligands

Abstract

A series of dinuclear half‐sandwich Ru(II), Os(II) and Ir(III) complexes [Ru2(μ‐Ln)(η6‐pcym)2Cl2](PF6)2 (1, 4), [Os2(μ‐Ln)(η6‐pcym)2Cl2](PF6)2 (2, 5) and [Ir2(μ‐Ln)(η5‐Cp*)2Cl2](PF6)2 (3, 6), based on 4,4′‐biphenyl‐based bridging Schiff base ligands N,N′‐(biphenyl‐4,4′‐diyldimethylidyne)bis‐2‐(pyridin‐2‐yl)methanamine (L1; for 1–3) and N,N′‐(biphenyl‐4,4′‐diyldimethylidyne)bis‐2‐(pyridin‐2‐yl)ethanamine (L2; for 4–6) is reported; pcym = 1‐methyl‐4‐(propan‐2‐yl)benzene, Cp* = pentamethylcyclopentadienyl. The complexes were characterized by relevant analytical techniques (i.e. elemental analysis, FT‐IR, NMR, ESI‐MS), and their in vitro cytotoxicity was assessed at six cancerous and two non‐cancerous (healthy) human cell lines. Overall, complexes 4–6, containing the L2 bridging ligand, revealed higher cytotoxicity as compared with 1–3 and, thus, they were studied in greater detail. The best‐performing complex 6 exceeded at least twice the in vitro cytotoxicity of cisplatin and showed high selectivity towards the cancer cells over the normal ones, including the primary culture of human hepatocytes. In contrast to cisplatin, complexes 4–6 did not induce the cell cycle modification of the treated A2780 human ovarian carcinoma cells (studied by flow cytometry and Western blot analysis). High levels of superoxide anion were induced by complexes 4–6 at the A2780 cells. The levels of activated forms of Caspase‐3 and Caspase‐8 at the A2780 cells treated by Ru(II) complex 4 were comparable with cisplatin, while complexes 5 and 6 had only a minor effect on activation of these caspases.

Activation of the Ir–N(pyridine) Bond in Half-Sandwich Tethered Iridium(III) Complexes

“…Complexes of the general formula [Ir­(η 5 -Cp*R­(N,N)­Z] n + , where N,N is en, bipy, or phen and Z = halido or pyridine, which could represent the nontether versions of our half-sandwich tethered iridium­(III) complexes, have, in fact, been reported to present moderate activity, ranging from a few micromolar (similar to that of cisplatin) to >100 μM, in cell lines such us A2780 and A549 using similar cell viability protocols. Dinuclear half-sandwich iridium­(III) complexes, bearing extended π systems as chelating and bridging N,N ligands, have also been reported that exert cytotoxicity similar to that of cisplatin in a number of cell lines …”

Mixed-ligand copper(ii) complexes of guanidine derivatives containing ciprofloxacin: synthesis, characterization, DFT calculations, DNA interactions and biological activities

“…The concentration values at different time points (0–72 h) were plotted and k is given by the slope of the linear fit, while t 1/2 = ln(2)/ k . 27…”

Copper(II) Compounds of 4‐Nitrobenzohydrazide with Different Anions (ClO4−, NO3− and Br−): Synthesis, Characterization, DFT Calculations, DNA Interactions and Cytotoxic Properties

“…The concentration values at different time points (0-72 h) were plotted, and k is given by the slope of the linear fit, while t 1/2 = ln(2)/k. [45]…”