Résultat de la recherche
Synthesis and Anticancer Activity of Long-Chain Isonicotinic Ester Ligand-Containing Arene Ruthenium Complexes and Nanoparticles
Arene ruthenium complexes containing long-chain N-ligands L1 = NC5H4–4-COO–C6H4–4-O–(CH2)9–CH3 or L2 = NC5H4–4-COO–(CH2)10–O–C6H4–4-COO–C6H4–4-C6H4–4-CN derived from isonicotinic acid, of the type [(arene)Ru(L)Cl2] (arene = C6H6, L = L1: 1; arene = p-MeC6H4Pr i , L = L1: 2; arene = C6Me6, L = L1: 3; arene = C6H6, L = L2: 4; arene = p-MeC6H4Pr i , L = L2: 5; arene = C6Me6, L = L2: 6) have been synthesized from the corresponding [(arene)RuCl2]2 precursor with the long-chain N-ligand L in dichloromethane. Ruthenium nanoparticles stabilized by L1 have been prepared by the solvent-free reduction of 1 with hydrogen or by reducing [(arene)Ru(H2O)3]SO4 in ethanol in the presence of L1 with hydrogen. These complexes and nanoparticles show a high anticancer activity towards human ovarian cell lines, the highest cytotoxicity being obtained for complex 2 (IC50 = 2 μM for A2780 and 7 μM for A2780cisR).
Synthesis, Molecular Structure, and Anticancer Activity of Cationic Arene Ruthenium Metallarectangles
The cytotoxicities of a new series of cationic metallarectangles have been established in the A2780 ovarian cancer cell line. Interestingly, the large rectangles incorporating 1,2-bis(4-pyridyl)ethylene linkers are ca. 5 times more cytotoxic (IC50 ≤ 6 μM) than the 4,4-bipyridine analogues (IC50 ≥ 30 μM), thus suggesting a correlation between cytotoxicity and the size of the rectangle.
Water-soluble arene ruthenium complexes containing pyridinethiolato ligands: Synthesis, molecular structure, redox properties and anticancer activity of the cations [(?6-arene)Ru(p-SC5H4NH)3]2+
The cationic complexes [(?6-arene)Ru(SC5H4NH)3]2+, arene being C6H6 (1), MeC6H5 (2), p-iPrC6H4Me (3) or C6Me6 (4), have been synthesized from the reaction of 4-pyridinethiol with the corresponding precursor (?6-arene)2Ru2(?2-Cl)2Cl2 and isolated as the chloride salts. The single-crystal x-ray structure of [4](PF6)2 reveals three 4-pyridinethiol moieties coordinated to the ruthenium center through the sulfur atom, with the hydrogen atom transferred from the sulfur to the nitrogen atom. The electrochem. study of 1-4 shows a clear correlation between the Ru(II)/Ru(III) redox potentials and the no. of alkyl substituents at the arene ligand (E°' (RuII/III): 1 > 2 > 3 > 4), whereas the cytotoxicity towards A2780 ovarian cancer cells follows the series 4 > 1 > 3 > 2, the hexamethylbenzene deriv. 4 being the most cytotoxic one. The corresponding reaction of the ortho-isomer, 2-pyridinethiol, with (?6-C6Me6)2Ru2(?2-Cl)2Cl2 does not lead to the expected 2-pyridinethiolato analog, but yields the neutral complex (?6-C6Me6)Ru(?2-SC5H4N)(?1-SC5H4N) (5). The analogous complex (?6-C6Me6)Ru(?2-SC9H6N)-(?1-SC9H6N) (6) is obtained from the similar reaction with 2-quinolinethiol. [on SciFinder(R)]
Synthesis, Molecular Structure, and Anticancer Activity of Cationic Arene Ruthenium Metallarectangles
Cationic arene ruthenium-based tetranuclear complexes comprising rectangular structures have been obtained from the dinuclear arene ruthenium complexes [Ru2(arene)2(OO?OO)2Cl2] (arene = p-cymene, hexamethylbenzene; OO?OO = 2,5-dihydroxy-1,4-benzoquinonato, 2,5-dichloro-1,4-benzoquinonato) by reaction with pyrazine or bipyridine linkers (N?N = pyrazine, 4,4'-bipyridine, 1,2-bis(4-pyridyl)ethylene) in methanol in the presence of AgO3SCF3, forming tetranuclear cations of general formula [Ru4(arene)4(N?N)2(OO?OO)2]4+. All complexes were isolated in good yield as triflate salts and were characterized by NMR and IR spectroscopy and studied by cyclic voltammetry. The cytotoxicities of the water-sol. compds. of the 4,4'-bipyridine and 1,2-bis(4-pyridyl)ethylene series have been established using ovarian A2780 cancer cells. The large rectangles incorporating 1,2-bis(4-pyridyl)ethylene linkers are ca. 5 times more cytotoxic (IC50 ? 6 ?M) than the 4,4'-bipyridine-contg. cations (IC50 ? 30 ?M). Structural characterization by x-ray diffraction of two representative compds., i.e., the triflate salts of [Ru4(hexamethylbenzene)4(4,4'-bipyridine)2(2,5-dihydroxy-1,4-benzoquinonato)2]4+and [Ru4(hexamethylbenzene)4(1,2-bis(4-pyridyl)ethylene)2(2,5-dichloro-1,4-benzoquinonato)2]4+, reveals differently sized cavities, different flexibilities, and different packing arrangements, suggesting a correlation between these structural properties and the obsd. cytotoxicities. [on SciFinder(R)]
Arene–ruthenium complexes with ferrocene-derived ligands: Synthesis and characterization of complexes of the type [Ru(η6-arene)(NC5H4CH2NHOC-C5H4FeC5H5)Cl2] and [Ru(η6-arene)(NC3H3N(CH2)2O2C–C5H4FeC5H5)Cl2]
Arene–ruthenium complexes of general formula [Ru(η6-arene)(L)Cl2] where L = NC5H4CH2NHOC-C5H4FeC5H5, arene = p-iPrC6H4Me (1) or C6Me6 (2); L = NC3H3N(CH2) 2O2C–C5H4FeC5H5, arene = p-iPrC6H4Me (3) or C6Me6 (4), and diruthenium–arene complexes of general formula [Ru(η6-arene)Cl2] 2 (L) where L = 1,1′-(NC5H4CH2NHOC)2-C5H4FeC5H4, arene = p-iPrC6H4Me (5) or C6Me6 (6); L = 1,1′-(NC3H3N(CH2)2O2C)2–C5H4FeC5H4, arene = p-iPrC6H4Me (7) or C6Me6 (8) have been synthesized and characterized. The molecular structures of 1 and 3 were confirmed by single-crystal X-ray diffraction. The in vitro anticancer activities of complexes 1–8 have been studied comparatively to the uncoordinated ligands. The complexes exhibit fairly low cytotoxicities in comparison to related ferrocene-derived arene–ruthenium complexes.
Water-soluble arene ruthenium complexes containing pyridinethiolato ligands: Synthesis, molecular structure, redox properties and anticancer activity of the cations [(η6-arene)Ru(p-SC5H4NH)3]2+
The cationic complexes [(η6-arene)Ru(SC5H4NH)3]2+, arene being C6H6 (1), MeC6H5 (2), p-iPrC6H4Me (3) or C6Me6 (4), have been synthesised from the reaction of 4-pyridinethiol with the corresponding precursor (η6-arene)2Ru2 (μ2-Cl)2Cl2 and isolated as the chloride salts. The single-crystal X-ray structure of [4](PF6)2 reveals three 4-pyridinethiol moieties coordinated to the ruthenium centre through the sulphur atom, with the hydrogen atom transferred from the sulphur to the nitrogen atom. The electrochemical study of 1–4 shows a clear correlation between the Ru(II)/Ru(III) redox potentials and the number of alkyl substituents at the arene ligand (E°′ (RuII/III): 1 > 2 > 3 > 4), whereas the cytotoxicity towards A2780 ovarian cancer cells follows the series 4 > 1 > 3 > 2, the hexamethylbenzene derivative 4 being the most cytotoxic one. The corresponding reaction of the ortho-isomer, 2-pyridinethiol, with (η6-C6Me6)2Ru2 (μ2-Cl)2Cl2 does not lead to the expected 2-pyridinethiolato analogue, but yields the neutral complex (η6-C6Me6)Ru(η2-SC5H4N)(η1-SC5H4N) (5). The analogous complex (η6-C6Me6)Ru(η2-SC9H6N)-(η1-SC9H6N) (6) is obtained from the similar reaction with 2-quinolinethiol.
Arene-ruthenium complexes with ferrocene-derived ligands: Synthesis and characterization of complexes of the type [Ru(?6-arene)(NC5H4CH2NHOC-C5H4FeC5H5)Cl2] and [Ru(?6-arene)(NC3H3N(CH2)2O2C-C5H4FeC5H5)Cl2]
Pyridylferrocene and imidazolylferrocene arene-Ru complexes [Ru(?6-arene)(L)Cl2] where L = NC5H4CH2NHOCC5H4FeC5H5, arene = p-iPrC6H4Me (1) or C6Me6 (2); L = NC3H3N(CH2)2O2CC5H4FeC5H5, arene = p-iPrC6H4Me (3) or C6Me6 (4), and diruthenium-arene complexes [Ru(?6-arene)Cl2]2(L) where L = 1,1'-(NC5H4CH2NHOC)2C5H4FeC5H4, arene = p-iPrC6H4Me (5) or C6Me6 (6); L = 1,1'-(NC3H3N(CH2)2O2C)2C5H4FeC5H4, arene = p-iPrC6H4Me (7) or C6Me6 (8) were synthesized and characterized. The mol. structures of 1 and 3 were confirmed by single-crystal x-ray diffraction. The in vitro anticancer activities of complexes 1-8 were studied comparatively to the uncoordinated ligands. The complexes exhibit fairly low cytotoxicities in comparison to related ferrocene-derived arene-Ru complexes. [on SciFinder(R)]
The "complex-in-a-complex" cations [(acac)2M?Ru6-(p-iPrC6H4Me)6(tpt)2(dhbq)3]6+: a trojan horse for cancer cells
The cytotoxicities of the large cationic arene-ruthenium prismatic cage [Ru6(p-iPrC6H4Me)6(tpt)2(dhbq)3]6+ (tpt = 2,4,6-tris(pyridin-4-yl)-1,3,5-triazine, dhbq = 2,5-dihydroxy-1,4-benzoquinolato; 16+), and its "complex-in-a-complex" derivs. [(acac)2M-1]6+ (M = Pd, Pt; acac = acetylacetonate), are evaluated in comparison with free [M(acac)2]. The differences in cytotoxicity suggest that, like a "Trojan Horse", leaching of the guest from the cage once inside a cell accelerates and increases the cytotoxic effect. [on SciFinder(R)]