Rhodium(III) and iridium(III) complexes with 1,2-naphthoquinone-1-oximate as a bidentate ligand: synthesis, structure, and biological activity

Abstract

The synthesis and characterization of three novel iridium(III) complexes and one rhodium(III) complex with 1-nitroso-2-naphthol (3) chelating as a 1,2-naphthoquinone-1-oximato ligand are described. The reaction of mu(2)-halogenido-bridged dimers [(eta(5)-C(5)Me(5))IrX(2)](2) [X is Cl (1a), Br (1b), I (1c)] and [(eta(5)-C(5)Me(5))RhCl(2)](2) (2a) with 3 in CH(2)Cl(2) yields the mononuclear complexes (eta(5)-C(5)Me(5))IrX(eta(2)-C(10)H(6)N(2)O) (4a, 4b, 4c) and (eta(5)-C(5)Me(5))RhCl(eta(2)-C(10)H(6)N(2)O) (5a). All compounds were characterized by their (1)H and (13)C NMR, IR, and mass spectra, UV/vis spectra were recorded for 4a and 5a. The X-ray structure analyses revealed a pseudo-octahedral "piano-stool" configuration for the metals with bidentate coordination through oximato-N and naphthoquinone-O, forming a nearly planar five-membered metallacycle. The metal complexes 4a and 5a were evaluated in respect to their cytotoxicity and binding affinity toward double-stranded DNA. As determined in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, both exerted a much stronger cytotoxic effect toward HeLa and HL60 cancer cell lines than did cisplatin. The remarkable cytotoxicity of the compounds tested may be attributed to necrosis, rather than to apoptosis, as it is evidenced by the caspase-3/7 activation assay. No clear evidence was found for interaction with double-stranded DNA. The melting experiments showed no significant differences between thermodynamic parameters of intact DNA and DNA incubated with 3, 4a, or 5a, although these derivatives altered DNA recognition by the BamHI restriction enzyme. Therefore, the screened iridium and rhodium complexes 4a and 5a may still be interesting as potential anticancer drugs owing to their high cytotoxicity toward cancer cell lines, whereas they do not modify DNA in a way similar to that of cisplatin.

Synthesis and DNA-binding properties of apoptosis-inducing cytotoxic half-sandwich rhodium(III) complexes with methyl-substituted polypyridyl ligands

“…Their IC 50 values decrease in the ligand order phen, dpq > dppz > dppn from 4.7/5.1 over 1.5 to 0.8 mM [7]. Marked in vitro cytotoxicity has also recently been reported for analogous (h 5 -C 5 Me 5 )M(III) (M ¼ Rh, Ir) complexes containing the chelating ligands 2-(pyridine-2-yl)thiazole (towards the A2780 and A2780cisR cell lines) [8] and 1,2-naphthoquinone-1-oximate (towards the HeLa and HL60 cell lines) [9].…”

“…Cell death inducing properties for the human cancer cell lines MCF-7 and HT-29 (colon carcinoma) have also been established for rhodium (III) complexes of the type [(coligand)RhCl(pp)](CF 3 SO 3 ) containing the facial coligands 1,4,7-trithiacyclononane ( [9]aneS 3 ) [10] and tris (pyrazolyl)methane (tpm) [11]. Several interesting structureeactivity relationships are apparent on comparison of the IC 50 values for rhodium(III) complexes containing different tridentate coligands.…”

Cellular impact and selectivity of half-sandwich organorhodium(III) anticancer complexes and their organoiridium(III) and trichloridorhodium(III) counterparts

“…In contrast, {(g 5 -C 5 Me 5 )Rh(III)} 2? complexes [5][6][7][8][9] and their Ir(III) analogues [7][8][9][10][11] containing polypyridyl and other chelating aromatic ligands were subsequently found to exhibit IC 50 values in the low micromolar range. Promising cell-deathinducing properties have also been established for Rh(III) complexes containing the facial j 3 S and j 3 N coligands 1,4,7-trithiacyclononane ( [9]aneS 3 ) [12,13] and tris(pyrazolyl)-methane (tpm) [14], as well as for the meridional trichlorido complexes mer-[RhCl 3 (DMSO)(pp)] (DMSO is dimethyl sulfoxide, pp is polypyridyl) [15,16].…”

“…Whereas flow-cytometric measurements of DNA fragmentation have previously indicated that both 1 and its 5,6-Me 2 phen analogue 2 (Scheme 2) induce specific apoptotic cell death in BJAB lymphoma cells [6], the pronounced cytotoxicity of [(g 5 -C 5 Me 5 )RhCl(1,2-naphthoquinone-1-oximate)] towards the HeLa and HL60 cell lines was attributed to necrosis [8]. To further elucidate the nature of their cell death mechanisms, we have now investigated the impact of complexes 1 and 2 on both adherent MCF-7 cells and nonadherent Jurkat leukemia cells, and compared this with the effects of similar trichloridorhodium(III) complexes.…”

Synthesis and in vitro antitumor activity of novel iridium(III) complexes with enantiopure C2-symmetrical vicinal diamine ligands

“…These findings are consistent with the general assumption that the extreme inertness of these iridium(III) complexes is correlated with an absence of cytotoxic effects on human tumor cell lines. [8][9][10] However, recent studies have demonstrated that some trichloridoiridium(III) polypyridyl complexes [11][12][13] and organometallic iridium(III) complexes containing negatively charged pentamethylcyclopentadienyl ligand [14][15][16][17][18][19][20][21][22] have shown promising anticancer activity. Additionally, a review has summarized recent work using iridium(III) complexes as anticancer drugs, focusing on the cytotoxic activity, cellular uptake efficiency, and mechanisms of these complexes.…”