Résultat de la recherche
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.
Mono and dinuclear rhodium, iridium and ruthenium complexes containing chelating 2,2′-bipyrimidine ligands: Synthesis, molecular structure, electrochemistry and catalytic properties
The mononuclear cations [(η5-C5Me5)RhCl(bpym)]+ (1), [(η5-C5Me5)IrCl(bpym)]+ (2), [(η6-p-PriC6H4Me)RuCl(bpym)]+ (3) and [(η6-C6Me6)RuCl(bpym)]+ (4) as well as the dinuclear dications [{(η5-C5Me5)RhCl}2 (bpym)]2+ (5), [{(η5-C5Me5)IrCl}2 (bpym)]2+ (6), [{(η6-p-PriC6H4Me)RuCl}2 (bpym)]2+ (7) and [{(η6-C6Me6)RuCl}2 (bpym)]2+ (8) have been synthesised from 2,2′-bipyrimidine (bpym) and the corresponding chloro complexes [(η5-C5Me5)RhCl2]2, [(η5-C5Me5)IrCl2]2, [(η6-PriC6H4Me)RuCl2]2 and [(η6-C6Me6)RuCl2]2, respectively. The X-ray crystal structure analyses of [3][PF6], [5][PF6]2, [6][CF3SO3]2 and [7][PF6]2 reveal a typical piano-stool geometry around the metal centres; in the dinuclear complexes the chloro ligands attached to the two metal centres are found to be, with respect to each other, cis oriented for 5 and 6 but trans for 7. The electrochemical behaviour of 1–8 has been studied by voltammetric methods. In addition, the catalytic potential of 1–8 for transfer hydrogenation reactions in aqueous solution has been evaluated: All complexes catalyse the reaction of acetophenone with formic acid to give phenylethanol and carbon dioxide. For both the mononuclear and dinuclear series the best results were obtained (50 °C, pH 4) with rhodium complexes, giving turnover frequencies of 10.5 h−1 for 1 and 19 h−1 for 5.
Water-Soluble Phenanthroline Complexes of Rhodium, Iridium and Ruthenium for the Regeneration of NADH in the Enzymatic Reduction of Ketones
The nicotinamide coenzyme NADH, consumed in enantioselective reduction of ketones catalysed by alcohol dehydrogenases, needs to be regenerated in order to maintain enzymatic activity. We therefore studied the catalytic potential of the cationic complexes [(η5-C5Me5)Rh(N∩N)Cl]+ (1: N∩N = 1,10-phenanthroline; 2: N∩N = 5-nitro-1,10-phenanthroline; 3: N∩N = 5-amino-1,10-phenanthroline), [(η5-C5Me5)Ir(N∩N)Cl]+ (4: N∩N = 5-nitro-1,10-phenanthroline) and [(η6-C6Me6)Ru(N∩N)Cl]+ (5: N∩N = 5-nitro-1,10-phenanthroline), isolated as the water-soluble chloride salts, for transfer hydrogenation of NAD+ to give NADH in aqueous solution. The best results were obtained with rhodium complex 1, which gave catalytic turnover frequencies up to 2000 h-1 in aqueous solution at pH 7 and 60 °C with sodium formate as the hydrogen source. When this NADH-regenerating catalytic system is combined with NADH-dependent enzymes, it is possible to chemoenzymatically reduce prochiral ketones such as acetophenone or 4-phenylbutan-2-one with high enantioselectivity. Combination of horse liver alcohol dehydrogenase (HLADH) or alcohol dehydrogenase from Rhodococcus sp. (S-ADH) with 1/formate as the NADH-regenerating system resulted in ee values up to 98 %, depending on the nature of the substrate and the enzyme. In order to explain the different catalytic activities, the electrochemical behaviour of complexes 1-5 has been studied.
Relating catalytic activity and electrochemical properties: The case of arene–ruthenium phenanthroline complexes catalytically active in transfer hydrogenation
The electrochemical properties of cationic complexes [(η6-arene)Ru(N ∩ N)Cl]Cl (arene/N ∩ N = C6H6/1,10-phenanthroline (1), p-MeC6H4Pri/1,10-phenanthroline (2), C6Me6/1,10-phenanthroline (3), C6Me6/5-NO2-1,10-phenanthroline (4), and C6Me6/5-NH2-1,10-phenanthroline (5)) were studied by cyclic voltammetry in order to rationalize catalytic activity in transfer hydrogenation of the respective aqua complexes [(η6-arene)Ru(N ∩ N)(OH2)](BF4)2 (6–10). Complexes 1–5 were chosen because the ‘true’ catalysts 6–10 are unstable under the conditions of the measurement. The electrochemical behaviour of 1–5 in acetonitrile solution is rather complicated due to consecutive and parallel chemical reactions that accompany electron transfer processes. Nonetheless, interpretation of the electrochemical data allowed to assess the influence of the structure and substitution on the redox and catalytic properties: the catalytic ability correlates with the reduction potentials, indicating the decisive role of the η6-arene ring directly bonded to the catalytic centre (Ru).
Sawhorse-type diruthenium tetracarbonyl complexes containing porphyrin-derived ligands as highly selective photosensitizers for female reproductive cancer cells
Diruthenium tetracarbonyl complexes of the type [Ru2 (CO)4(μ2-η2-O2CR)2L2] containing a Ru–Ru backbone with four equatorial carbonyl ligands, two carboxylato bridges, and two axial two-electron ligands in a sawhorse-like geometry have been synthesized with porphyrin-derived substituents in the axial ligands [1: R is CH3, L is 5-(4-pyridyl)-10,15,20-triphenyl-21,23H-porphyrin], in the bridging carboxylato ligands [2: RCO2H is 5-(4-carboxyphenyl)-10,15,20-triphenyl-21,23H-porphyrin, L is PPh3; 3: RCO2H is 5-(4-carboxyphenyl)-10,15,20-triphenyl-21,23H-porphyrin, L is 1,3,5-triaza-7-phosphatricyclo[3.3.1.1]decane], or in both positions [4: RCO2H is 5-(4-carboxyphenyl)-10,15,20-triphenyl-21,23H-porphyrin, L is 5-(4-pyridyl)-10,15,20-triphenyl-21,23H-porphyrin]. Compounds 1–3 were assessed on different types of human cancer cells and normal cells. Their uptake by cells was quantified by fluorescence and checked by fluorescence microscopy. These compounds were taken up by human HeLa cervix and A2780 and Ovcar ovarian carcinoma cells but not by normal cells and other cancer cell lines (A549 pulmonary, Me300 melanoma, PC3 and LnCap prostate, KB head and neck, MDAMB231 and MCF7 breast, or HT29 colon cancer cells). The compounds demonstrated no cytotoxicity in the absence of laser irradiation but exhibited good phototoxicities in HeLa and A2780 cells when exposed to laser light at 652 nm, displaying an LD50 between 1.5 and 6.5 J/cm2 in these two cell lines and more than 15 J/cm2 for the others. Thus, these types of porphyric compound present specificity for cancer cell lines of the female reproductive system and not for normal cells; thus being promising new organometallic photosensitizers.
Synthesis, structure and electrochemistry of cationic diruthenium complexes of the type [(N∩N)2Ru2 (CO)2 (μ-CO)2(μ-OOCFc)]+ containing a ferrocenecarboxylato bridge and two chelating aromatic diimine ligands
The dinuclear bis(ferrocenecarboxylato) complex Ru2 (CO)4 (μ-OOCFc)2 (py)2 (Fc = ferrocenyl, py = pyridine) was found to react with aromatic diimines (2,2′-dipyridyl, 4,4′-dimethyl-2,2′-dipyridyl, 1,10-phenanthroline, 5-nitro-1,10-phenanthroline, and 5-amino-1,10-phenanthroline) in methanol to give the cationic diruthenium complexes [(N∩N)2Ru2 (CO)2 (μ-CO)2(μ-OOCFc)]+ (1: N∩N = 2,2′-dipyridyl, 2: N∩N = 4,4′-dimethyl-2,2′-dipyridyl, 3: N∩N = 1,10-phenanthroline, 4: N∩N = 5-nitro-1,10-phenanthroline, 5: N∩N = 5-amino-1,10-phenanthroline), which have been isolated as the hexafluorophosphate salts. The molecular structure of 3, solved by single-crystal X-ray analysis of the tetraphenylborate salt [3][BPh4], shows a diruthenium backbone bridged by two carbonyl and by one ferrocenecarboxylato ligand, the two 1,10-phenanthroline ligands being in the axial positions. Cyclic voltammetry in dichloromethane reveals for all compounds two successive oxidations due to ferrocene/ferrocenium redox couple and oxidation of the diruthenium core.
Dinuclear ruthenium sawhorse-type complexes containing carboxylato bridges and ferrocenyl substituents: Synthesis and electrochemistry
The ferrocenyl-containing diruthenium complexes [Ru2(CO)4(μ2-η2-OOCFc)2L2] (Fc = ferrocenyl, fc = ferrocen-1,1′-diyl; 1: L = NC5H4–COOC6H4–OC10H21, 2: L = NC5H4–COOC6H4–OC16H33, 3: L = NC5H4–OOC–fc–C12H25) and [Ru2(CO)4(μ2-η2-OOC6H5)2(NC5H4–OOC–fc–C12H25)2] (4) have been synthesized from Ru3(CO)12, ferrocene carboxylic or benzoic acid and the corresponding pyridine derivative. The synthesis of the new pyridine derivative NC5H4–OOC–fc–C12H25 used for the preparation of 3 and 4 is also reported. Complexes 1–4 posses a so-called sawhorse structure consisting of the Ru2(CO)4 backbone and two bridging carboxylato ligands, while the coordination sphere around the ruthenium atoms is completed by the pyridine-derived ligands bonded in the axial positions. The electrochemical behavior of 1–4 and their known analogues [Ru2(CO)4(μ2-η2-OOCFc)2L2] (5: L = NC5H5, 6: L = P(C6H5)3, 7: L = NC5H4–OOCFc) has been studied by voltammetry on rotating disc electrode and by cyclic voltammetry.
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.
Mono and dinuclear iridium, rhodium and ruthenium complexes containing chelating carboxylato pyrazine ligands: Synthesis, molecular structure and electrochemistry
The mononuclear complexes [(η5-C5Me5)IrCl(L1)] (1), [(η5-C5Me5)RhCl(L1)] (2), [(η6-p-PriC6H4Me)RuCl(L1)] (3) and [(η6-C6Me6)RuCl(L1)] (4) have been synthesised from pyrazine-2-carboxylic acid (HL1) and the corresponding complexes [{(η5-C5Me5)IrCl2}2], [{(η5-C5Me5)RhCl2}2], [{(η6-p-PriC6H4Me)RuCl2}2], and [{(η6-C6Me6)RuCl2}2], respectively. The related dinuclear complexes [{(η5-C5Me5)IrCl}2 (μ-L2)] (5), [{(η5-C5Me5)RhCl}2 (μ-L2)] (6), [{(η6-p-PriC6H4Me)RuCl}2 (μ-L2)] (7) and [{(η6-C6Me6)RuCl}2 (μ-L2)] (8) have been obtained in a similar manner from pyrazine-2,5-dicarboxylic acid (H2L2). Compounds isomeric to the latter series, [{(η5-C5Me5)IrCl}2 (μ-L3)] (9), [{(η5-C5Me5)RhCl}2 (μ-L3)] (10), [{(p-PriC6H4Me)RuCl}2 (μ-L3)] (11) and [{(η6-C6Me6)RuCl}2 (μ-L3)] (12), have been prepared by using pyrazine-2,3-dicarboxylic acid (H2L3) instead of H2L2. The molecular structures of 2 and 3, determined by X-ray diffraction analysis, show the pyrazine-2-carboxylato moiety to act as an N,O-chelating ligand, while the structure analyses of 5–7, confirm that the pyrazine-2,5-dicarboxylato unit bridges two metal centres. The electrochemical behaviour of selected representatives has been studied by voltammetric techniques.
Dinuclear hexamethylbenzene ruthenium cations containing η1:η2-2-(ferrocenyl)ethen-1-yl ligands: Synthesis, structure, electrochemistry
The cationic ferrocenyl-containing complexes [(η6-C6Me6)2Ru2 (μ-η1:η2-CH–CHFc)2 (μ-H)]+ (3) and [(η6-C6Me6)2Ru2 (μ-PPh2)(μ-η1:η2-CH–CHFc)(μ-H)]+ (4) have been synthesised in ethanol from ethynylferrocene and the dinuclear precursors [(η6-C6Me6)2Ru2 (μ-H)3]+ (1) and [(η6-C6Me6)2Ru2(μ-PPh2)(μ-H)2]+ (2) respectively, and isolated as tetrafluoroborate salts. The spectroscopic data of 3 and 4 as well as the single-crystal X-ray diffraction analysis of [4][BF4] show that the alkyne function of ethynylferrocene has been converted to a σ/π-ethenyl ligand by transfer of a bridging hydride from the diruthenium backbone onto the α-carbon of the triple bond in ethynylferrocene. The ferrocenyl-containing diruthenium compounds [3][BF4] and [4][BF4] as well as their parent compounds [1][BF4] and [2][BF4] have been studied by voltammetric techniques: Whereas 1 shows only an irreversible Ru(II)/Ru(III) oxidation, the phosphido-bridged derivative 2 displays two well-separated one-electron redox processes. In the case of 3 and 4, the ferrocenyl substituents give rise to additional reversible ferrocene/ferrocenium waves.