Water-soluble Arene Ruthenium Research Articles

Synthesis and characterization of water-soluble arene-ruthenium complexes and their application in biphasic olefin oxidation

New water-soluble complexes [(η6-C6H6)RuCl(C5H4N-2-CH = N-R)]Cl (1) (with R = 4-hydroxymethylphenyl (a), 2,4-dichlorophenyl (b), 2-fluorophenyl (c), 3-carboxyphenyl (d)) have been synthesized by reacting [(η6-C6H6)Ru(μ-Cl)Cl]2 with the N,N′-bidentate ligands in a 1:2 ratio. Full characterization of all complexes was accomplished using 1H and 13C NMR, elemental analyses, UV-Vis spectroscopy, IR spectroscopy and single crystal X-ray crystallography for determination of the structure of 1d, as 1d·4H2O. The single crystal structure confirmed coordination of the ligand to the ruthenium(II) center leading to a structure commonly described as a pseudo-octahedral, three-legged piano stool. The geometry around the Ru(II) center is such that the arene ring occupies the apex of the stool while the N,N′-bidentate ligand and a chloride occupy the base of the stool. The synthesized Ru(II) complexes were tested as catalysts for oxidation of styrene using NaIO4 as a co-oxidant in a biphasic system. All complexes were active, giving good yields of benzaldehyde. Catalyst 1c was later investigated for olefin oxidation and gave high yields of the corresponding aldehydes as the major products in all cases.

Synthesis and reactivity of water-soluble arene–ruthenium(II) complexes and dimerization of terminal alkynes in organic and aqueous media

Treatment of the dimeric precursor [{RuCl(μ-Cl) (η6-C6H5OCH2CH2OH)}2] (1) with HNCPh2 in the presence of H2O afforded the arene–ruthenium(II) complex [(η6-C6H5OCH2CH2OH) (HN]CPh2)RuCl2] (2), as well as the aquo-species [(η6-C6H5OCH2CH2OH) (H2O)RuCl2] (3). The hydroxyethoxy substituent on the arene induces water-solubility of the resulting complexes. Reaction of 2 with HCC(O)OR1 in R2OH afforded the chelate vinyl ether complexes [Tp(PPh3)Ru–C(OR2)CHC(O)OR1] (4a, R1 = Me, R2 = Me; 4b, R1 = Et, R2 = Me; 4c, R1 = Et, R2 = Et; 4d, R1 = Me, R2 = Et), respectively. Preliminary results on the catalytic activity of 2 are also accessible. Intriguingly, complex 2 catalyzes the dimerization of some terminal alkynes HCCR in organic and aqueous medium. Whereas with R = COOMe, E-selective head-to-head dimerization takes place exclusively, in the case of R = SiMe3, t-Bu isomeric mixtures of head-to-head and head-to-tail coupling products are obtained. The structure of 3 has been determined by X-ray diffraction analysis.

Water-soluble arene ruthenium complexes: From serendipity to catalysis and drug design

Shortly after the discovery of benzene ruthenium dichloride and some controversy about its polymeric or dimeric nature in the 1960s, the hydrolysis of this material in water to give a mixture of benzene ruthenium aqua complexes was discovered. However, it took a long time until this reaction and the hydrolysis of other arene analogs were used as an entry to the synthesis of water-soluble arene ruthenium complexes. These complexes are able to activate molecular hydrogen in aqueous solution and allow the design of arene ruthenium bioconjugates. They can serve as catalysts or catalyst precursors for hydrogenation and transfer hydrogenation reactions in water and they are at present one of the most promising classes of metal complexes to replace cisplatin in future cancer therapy, due to their inherent cytotoxicity and their good cellular uptake, conditioned by well balanced lipophilic and hydrophilic properties.

Encapsulation of hydrophobic pyrenyl­cycloplatinate complexes within a water-soluble arene ruthenium metalla­cage

Two hydrophobic pyrenyl-containing cycloplatinate complexes (2-(1-pyrenyl)pyridine)Pt(acac) (Pt-1) and {2-(4-(1-pyrenyl)phenyl)pyridine}Pt(acac) (Pt-2) (acac = acetylacetonato) have been encapsulated in the hexacationic water-soluble metalla-cage [(p-cymene)(6)Ru-6(donq)(3)(tpt)(2)](6+) (donq = 5,8-dioxydo-1,4-naphthoquinonato, tpt = 2,4,6-tri(pyridin-4-yl)-1,3,5-triazine). The host-guest systems [(Pt-1)subset of cage](6+) and [(Pt-2)subset of cage](6+) have been characterized by NMR and UV-visible spectroscopy, thus confirming the encapsulation of the platinum complexes in the hexa-ruthenium metalla-cage. In addition, the cytotoxicities of the complex-in-a-complex systems have been established using human ovarian A2780 and A2780cisR cancer cell lines. This study shows IC50 values in the lower micromolar range for both compounds and on both cancer cell lines (IC50 approximate to 1 mu M): These values being higher than the empty metalla-cage which possesses an IC50 > 3 mu M. This amplified overall cytotoxicity for the complex-in-a-complex systems suggests an efficient delivery of the hydrophobic complexes by the water-soluble arene ruthenium metalla-cage. (C) 2012 Elsevier B.V. All rights reserved.

Cellular delivery of pyrenyl-arene ruthenium complexes by a water-soluble arene ruthenium metalla-cage

Three pyrenyl-arene ruthenium complexes (M(1)-M(3)) of the general formula [Ru(η(6)-arene-pyrenyl)Cl(2)(pta)] (pta = 1,3,5-triaza-7-phosphaadamantane) have been synthesised and characterised. Prior to the coordination to ruthenium, pyrene was connected to the arene ligand via an alkane chain containing different functional groups: ester (L(1)), ether (L(2)) and amide (L(3)), respectively. Furthermore, the pyrenyl moieties of the M(n) complexes were encapsulated within the hydrophobic cavity of the water soluble metalla-cage, [Ru(6)(η(6)-p-cymene)(6)(tpt)(2)(donq)(3)](6+) (tpt = 2,4,6-tri-(pyridin-4-yl)-1,3,5-triazine; donq = 5,8-dioxydo-1,4-naphthoquinonato), while the arene ruthenium end was pointing out of the cage, thus giving rise to the corresponding host-guest systems [M(n)⊂Ru(6)(η(6)-p-cymene)(6)(tpt)(2)(donq)(3)](6+) ([M(n)⊂cage](6+)). The antitumor activity of the pyrenyl-arene ruthenium complexes (M(n)) and the corresponding host-guest systems [M(n)⊂cage][CF(3)SO(3)](6) were evaluated in vitro in different types of human cancer cell lines (A549, A2780, A2780cisR, Me300 and HeLa). Complex M(2), which contains an ether group within the alkane chain, demonstrated at least a 10 times higher cytotoxicity than the reference compound [Ru(η(6)-p-cymene)Cl(2)(pta)] (RAPTA-C). All host-guest systems [M(n)⊂cage](6+) showed good anticancer activity with IC(50) values ranging from 2 to 8 μM after 72 h exposure. The fluorescence of the pyrenyl moiety allowed the monitoring of the cellular uptake and revealed an increase of uptake by a factor two of the M(2) complex when encapsulated in the metalla-cage [Ru(6)(η(6)-p-cymene)(6)(tpt)(2)(donq)(3)](6+).

Synthesis, spectral and structural studies of water soluble arene ruthenium (II) complexes containing 2,2′-dipyridyl- N-alkylimine ligand

A series of water soluble complexes of general formula [(η 6-arene)Ru{(C 5H 4N) 2CNRi}Cl]PF 6 have been prepared by the reaction of [{(η 6-arene)RuCl 2} 2] with appropriate 2,2′-dipyridyl- N-alkylimine ligands (dpNRi) in the presence of NH 4PF 6 (where; R = Me or Et; arene = p-cymene, C 6Me 6, C 6H 6). The 2,2′-dipyridyl- N-alkylimine ligands are prepared by reaction of 2,2′-dipyridyl ketone with the corresponding alkylamine. The complexes are readily obtained as air stable yellow to dark brown solids by simple stirring at room temperature. The complexes are isolated as their hexafluorophosphate salts and characterized on the basis of spectroscopic data. The molecular structure of representative complex [(η 6-C 6Me 6)Ru{(C 5H 4N) 2C N–Me}Cl]PF 6 has been determined by single crystal X-ray diffraction studies.

Water-soluble arene ruthenium complexes containing pyridinethiolato ligands: Synthesis, molecular structure, redox properties and anticancer activity of the cations [(η 6-arene)Ru( p-SC 5H 4NH) 3] 2+

The cationic complexes [(η 6-arene)Ru(SC 5H 4NH) 3] 2+, arene being C 6H 6 ( 1), MeC 6H 5 ( 2), p- i PrC 6H 4Me ( 3) or C 6Me 6 ( 4), have been synthesised from the reaction of 4-pyridinethiol with the corresponding precursor (η 6-arene) 2Ru 2(μ 2-Cl) 2Cl 2 and isolated as the chloride salts. The single-crystal X-ray structure of [ 4](PF 6) 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°′ (Ru II/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 (η 6-C 6Me 6) 2Ru 2(μ 2-Cl) 2Cl 2 does not lead to the expected 2-pyridinethiolato analogue, but yields the neutral complex (η 6-C 6Me 6)Ru(η 2-SC 5H 4N)(η 1-SC 5H 4N) ( 5). The analogous complex (η 6-C 6Me 6)Ru(η 2-SC 9H 6N)-(η 1-SC 9H 6N) ( 6) is obtained from the similar reaction with 2-quinolinethiol.

Water-soluble arene ruthenium catalysts containing sulfonated diamine ligands for asymmetric transfer hydrogenation of α-aryl ketones and imines in aqueous solution

A new family of nine cationic organometallic aqua complexes of the type [(arene)Ru(RSO2N∩NH2)(OH2)]+ (1–9), containing chiral N,N-chelating ligands, has been synthesised and isolated as the tetrafluoroborate salts, which are water-soluble and stable to hydrolysis. The enantiopure complexes 1–9 catalyse the transfer hydrogenation of prochiral aryl ketones and imines in aqueous solution to give the corresponding alcohols and amines with good conversion and enantioselectivity. This method gives an environmentally friendly access, for instance, to isoquinoline alkaloids by asymmetric catalysis in water.