Synthesis, Characterization, and in Vitro Evaluation of Novel Ruthenium(II) η⁶-Arene Imidazole Complexes

Abstract

Ten complexes of general formula [Ru(eta6-arene)Cl2(L)], [Ru(eta6-arene)Cl(L)2][X], and [Ru(eta6-arene)(L)3][X]2 (eta6-arene = benzene, p-cymene; L = imidazole, benzimidazole, N-methylimidazole, N-butylimidazole, N-vinylimidazole, N-benzoylimidazole; X = Cl, BF4, BPh4) have been prepared and characterized by spectroscopy. The structures of five representative compounds have been established in the solid state by single-crystal X-ray diffraction. All the new compounds were assessed by the same in vitro screening assays applied to [imidazole-H][trans-RuCl4(DMSO)(imidazole)] (NAMI-A) and [Ru(eta6-arene)Cl2(1,3,5-triaza-7-phosphaadamantane)] (RAPTA) compounds. It was found that the new compounds show essentially the same order of cytotoxicity as the RAPTA compounds toward cancer cells. Several of the compounds were selective toward cancer cells in that they were less (or not) cytotoxic toward nontumorigenic cells that are used to model healthy human cells. Thus, two of the compounds, [Ru(eta6-p-cymene)Cl(vinylimid)2][Cl] (vinylimid = N-vinylimidazole) and [Ru(eta6-benzene)(mimid)3][BF4]2 (mimid = N-methylimidazole), have been selected for a more detailed in vivo evaluation.

Synthesis, spectral characterization and anticancer studies of three novel ruthenium(III) 2,2′‐bipyridine complexes

“…Our results are similar to those reported by Vock et al . who tested ten ruthenium arene complexes with the general formula [Ru(eta6‐arene)Cl 2 (L)] (arene = benzene, p ‐cymene; L = imidazole, benzimidazole, N ‐methylimidazole, N ‐butylimidazole, N ‐vinylimidazole, N ‐benzoylimidazole; X = Cl, BF 4 , BPh 4 ) for their selectivity towards cancer cells in vitro .…”

Synthesis, spectral characterization and anticancer studies of three novel ruthenium(III) 2,2′‐bipyridine complexes

“…Our results are similar to those reported by Vock et al . who tested ten ruthenium arene complexes with the general formula [Ru(eta6‐arene)Cl 2 (L)] (arene = benzene, p ‐cymene; L = imidazole, benzimidazole, N ‐methylimidazole, N ‐butylimidazole, N ‐vinylimidazole, N ‐benzoylimidazole; X = Cl, BF 4 , BPh 4 ) for their selectivity towards cancer cells in vitro .…”

Synthesis, Characterization, and Biological Activity of Water-Soluble, Dual Anionic and Cationic Ruthenium–Arene Complexes Bearing Imidazol(in)ium-2-dithiocarboxylate Ligands

“…Metrics determined for the [RuCl 3 ­( p -cymene)] − anion from the molecular structures of complexes 3a and 3d were in good agreement with those reported previously for mixed organic/organometallic salts ,− and dual anionic and cationic complexes ,− featuring this moiety. The ruthenium atom exhibited a distorted octahedral geometry with the aromatic ring of the p -cymene ligand formally occupying three coordination sites and the three chlorido ligands occupying the remaining three facial positions.…”

Organoruthenium and Osmium Anticancer Complexes Bearing a Maleimide Functional Group: Reactivity to Cysteine, Stability, and Cytotoxicity

“…The RuI bond lengths in 2 c were 2.7153(4) and 2.7409(4) Å, and in the same range as the OsI bond lengths in 3 c with 2.7368(4) and 2.7223(4) Å, respectively. The RuN and OsN distances were 2.125(3) and 2.150(4) Å, respectively, which are comparable to those reported for similar complexes 13b,c. The NNH bond length in 2 c is slightly longer after coordination to the Ru center than in [H 2 ind] + (Hind=indazole) but similar to Hind in both cis ‐ and trans ‐configured [Ru(Hind)(NO)Cl 4 ](H 2 ind) complexes 14…”

Synthesis, spectral characterization and anticancer studies of three novel ruthenium(III) 2,2′‐bipyridine complexes

“…Our results are similar to those reported by Vock et al . who tested ten ruthenium arene complexes with the general formula [Ru(eta6‐arene)Cl 2 (L)] (arene = benzene, p ‐cymene; L = imidazole, benzimidazole, N ‐methylimidazole, N ‐butylimidazole, N ‐vinylimidazole, N ‐benzoylimidazole; X = Cl, BF 4 , BPh 4 ) for their selectivity towards cancer cells in vitro .…”

Synthesis, Characterization, and Biological Activity of Water-Soluble, Dual Anionic and Cationic Ruthenium–Arene Complexes Bearing Imidazol(in)ium-2-dithiocarboxylate Ligands

“…Metrics determined for the [RuCl 3 ­( p -cymene)] − anion from the molecular structures of complexes 3a and 3d were in good agreement with those reported previously for mixed organic/organometallic salts ,− and dual anionic and cationic complexes ,− featuring this moiety. The ruthenium atom exhibited a distorted octahedral geometry with the aromatic ring of the p -cymene ligand formally occupying three coordination sites and the three chlorido ligands occupying the remaining three facial positions.…”

Organoruthenium and Osmium Anticancer Complexes Bearing a Maleimide Functional Group: Reactivity to Cysteine, Stability, and Cytotoxicity

“…The RuI bond lengths in 2 c were 2.7153(4) and 2.7409(4) Å, and in the same range as the OsI bond lengths in 3 c with 2.7368(4) and 2.7223(4) Å, respectively. The RuN and OsN distances were 2.125(3) and 2.150(4) Å, respectively, which are comparable to those reported for similar complexes 13b,c. The NNH bond length in 2 c is slightly longer after coordination to the Ru center than in [H 2 ind] + (Hind=indazole) but similar to Hind in both cis ‐ and trans ‐configured [Ru(Hind)(NO)Cl 4 ](H 2 ind) complexes 14…”

Synthesis, spectral characterization and anticancer studies of three novel ruthenium(III) 2,2′‐bipyridine complexes

“…Our results are similar to those reported by Vock et al . who tested ten ruthenium arene complexes with the general formula [Ru(eta6‐arene)Cl 2 (L)] (arene = benzene, p ‐cymene; L = imidazole, benzimidazole, N ‐methylimidazole, N ‐butylimidazole, N ‐vinylimidazole, N ‐benzoylimidazole; X = Cl, BF 4 , BPh 4 ) for their selectivity towards cancer cells in vitro .…”

Synthesis, Characterization, and Biological Activity of Water-Soluble, Dual Anionic and Cationic Ruthenium–Arene Complexes Bearing Imidazol(in)ium-2-dithiocarboxylate Ligands

“…Metrics determined for the [RuCl 3 ­( p -cymene)] − anion from the molecular structures of complexes 3a and 3d were in good agreement with those reported previously for mixed organic/organometallic salts ,− and dual anionic and cationic complexes ,− featuring this moiety. The ruthenium atom exhibited a distorted octahedral geometry with the aromatic ring of the p -cymene ligand formally occupying three coordination sites and the three chlorido ligands occupying the remaining three facial positions.…”

Organoruthenium and Osmium Anticancer Complexes Bearing a Maleimide Functional Group: Reactivity to Cysteine, Stability, and Cytotoxicity

“…The RuI bond lengths in 2 c were 2.7153(4) and 2.7409(4) Å, and in the same range as the OsI bond lengths in 3 c with 2.7368(4) and 2.7223(4) Å, respectively. The RuN and OsN distances were 2.125(3) and 2.150(4) Å, respectively, which are comparable to those reported for similar complexes 13b,c. The NNH bond length in 2 c is slightly longer after coordination to the Ru center than in [H 2 ind] + (Hind=indazole) but similar to Hind in both cis ‐ and trans ‐configured [Ru(Hind)(NO)Cl 4 ](H 2 ind) complexes 14…”