Tetranuclear Ruthenium Complexes Research Articles

Tetranuclear Polypyridylruthenium(II) Complexes as Inhibitors and Down‐Regulators of Phosphatase Enzymes

AbstractMitogen‐activated protein kinase phosphatases (MKPs) are over‐expressed in many cancers. The increased levels of MKP enzymes protect cells from apoptosis induced by anticancer drugs, and thereby decrease the efficacy of the drug. Consequently, there is considerable interest in the development of agents that can down‐regulate the production of the MKP enzymes or inhibit their catalytic activities. We have examined the ability of a series of oligonuclear polypyridylruthenium(II) complexes to inhibit the activity of MKP‐1 and MKP‐3. The results demonstrated that two tetranuclear complexes inhibit the activity of MKP‐1 and MKP‐3 at 10‐20 μM concentrations. The ability of the ruthenium complexes to inhibit the production of MKP‐1 in live cancer cells was demonstrated through Western blotting assays, while real‐time reverse transcription polymerase chain reaction assays demonstrated the tetranuclear complexes decreased the amount of mkp‐1 mRNA produced in cancer cells. The results of this study suggest that tetranuclear ruthenium complexes could be used to enhance the antiproliferative effect of anticancer drugs.

Photostimulated oxidation of water catalyzed by a tetranuclear ruthenium complex with lithium countercations

Photostimulated oxidation of water by potassium persulfate in the presence of photosensitizer bpy3RuCl2 ∙ 6H2O and ruthenium catalyst Li10[{Ru4(μ-O)4(μ-OH)2(H2O)4} ∙ (γ-SiW10O36)2] ∙ 10H2O has been studied. It has been shown that the quantum yield of O2 (0.29) is much higher than the quantum yield in a similar photocatalytic system with rubidium countercations (0.09).

Non-innocence and mixed valency in tri- and tetranuclear ruthenium complexes of a heteroquinone bridging ligand.

The redox-active ligand 5,7,12,14-tetraazapentacene-6,13-quinone = L forms structurally characterised compounds with three (1) or four (2) [Ru(acac)2] complex fragments in which each of the metals is N,O-chelated. The new tris- and tetrakis-bidentate chelate compounds exhibit ruthenium centres bridged at about 4 Å by quinone O atoms which are then situated across the pentacene π system at about 6-8 Å distance. Several electron transfer processes were observed by voltammetry (CV, DPV) and the intermediates identified by EPR and UV-Vis-NIR spectroelectrochemistry. TD-DFT calculations were applied to assign the proper oxidation states within the multistep redox systems {(μn-L)[Ru(acac)2]n}k, n = 3 or 4, revealing both metal and ligand based electron transfer.

Oligonuclear polypyridylruthenium(II) complexes: selectivity between bacteria and eukaryotic cells.

The objectives of this study were to: (i) determine the in vitro activities of a series of di-, tri- and tetra-nuclear ruthenium complexes (Rubbn, Rubbn-tri and Rubbn-tetra) against a range of Gram-positive and -negative bacteria and compare the antimicrobial activities with the corresponding toxicities against eukaryotic cells; and (ii) compare MIC values with achievable in vivo serum concentrations for the least toxic ruthenium complex. The in vitro activities were determined by MIC assays and time-kill curve experiments, while the toxicities of the ruthenium complexes were determined using the Alamar blue cytotoxicity assay. A preliminary pharmacokinetic study was undertaken to determine the Rubb12 serum concentration in mice as a function of time after administration. Rubb12, Rubb12-tri and Rubb12-tetra are highly active, with MIC values of 1-2 mg/L (0.5-1.5 μM) for a range of Gram-positive strains, but showed variable activities against a panel of Gram-negative bacteria. Time-kill experiments indicated that Rubb12, Rubb12-tri and Rubb12-tetra are bactericidal and kill bacteria within 3-8 h. The di-, tri- and tetra-nuclear complexes were ∼50 times more toxic to Gram-positive bacteria and 25 times more toxic to Gram-negative strains, classified as susceptible, than to liver and kidney cells. Preliminary pharmacokinetic experiments established that serum concentrations higher than MIC values can be obtained for Rubb12 with an administered dose of 32 mg/kg. The ruthenium complexes, particularly Rubb12, have potential as new antimicrobial agents. The structure of the dinuclear ruthenium complex can be readily further modified in order to increase the selectivity for bacteria over eukaryotic cells.

Kinetics of water oxidation with cerium(IV) compounds catalyzed by a tetranuclear ruthenium complex

The kinetics and mechanism of water oxidation with cerium(IV) compounds catalyzed by a tetranuclear ruthenium complex containing two polyoxotungstate ligands are reported. Four water molecules are oxidized via an eight-electron process to form two oxygen molecules.

Gas phase reactivity of iron pentacarbonyl with anionic metal clusters

The anionic transition metal carbonyl cluster [H3Ru4(CO)12]− may be energized in the gas phase through collision-induced dissociation (CID), which results in sequential loss of hydrogen and carbon monoxide from the cluster. If this experiment is performed in the presence of iron pentacarbonyl gas, up to three equivalents of the iron complex add to the tetranuclear ruthenium complex to give nearly-saturated product clusters with cores containing five, six and seven metal atoms. Further CID reveals that the iron atoms become intimately incorporated into the cluster core, and thus this process represents a method for the gas-phase synthesis of mixed-metal clusters.

Water Oxidation Catalysis by Molecular Metal-Oxides

Water oxidation catalysis is recognized as the bottleneck for the development of efficient devices based on artificial photosynthesis, that is the light driven water splitting into hydrogen and oxygen. A recent breakthrough in this field, is the development of a molecular, fast and robust water oxidation catalyst namely a fully inorganic tetranuclear ruthenium complex with polyoxometalate ligands. The crystal structure of [Ru4(μ-O)4(μ-OH)2(H2O)4(SiW10O36)2]10-, 1, evidences the entrapment of an adamantane like, tetranuclear ruthenium(IV)-oxo core, by two decatungtosilicate units. Several spectroscopic techniques confirm the maintenance of the structure in aqueous solution. In the presence of Ce(IV) as sacrificial electron acceptor, 1 catalyzes water oxidation to oxygen, showing up to 500 turnovers and a turnover frequency of 0.125 s-1. The synergistic effect of the four ruthenium centres has a fundamental effect on such astounding performance, as confirmed by spectroscopic and computational characterization of five competent intermediates involved in the catalytic cycle, in strict analogy with the natural paradigm of the oxygen evolving centre in Photosystem II. Interestingly, 1 efficiently catalyzes water oxidation in the presence of photogenerated oxidants, as well; this fundamental feature is probably related to very fast hole scavenging of anionic 1 from cationic photogenerated oxidants, such as Ru(bpy)33+. Thus, 1 is an ideal candidate for the assembly of high efficient oxygenevolving anodes into nanostructured devices for artificial photosynthesis.

Synthesis, Structure, and Reactivity of New Tetranuclear Ru-Hbpp-Based Water-Oxidation Catalysts

The preparation of three new octadentate tetranucleating ligands made out of two Ru-Hbpp-based units [where Hbpp is 3,5(bispyridyl)pyrazole], linked by a xylyl group attached at the pyrazolate moiety, of general formula (Hbpp)(2)-u-xyl (u = p, m, or o) is reported, together with its dinucleating counterpart substituted at the same position with a benzyl group, Hbpp-bz. All of these ligands have been characterized with the usual analytical and spectroscopic techniques. The corresponding tetranuclear ruthenium complexes of general formula {[Ru(2)(trpy)(2)(L)](2)(μ-(bpp)(2)-u-xyl)}(n+) [L = Cl or OAc, n = 4; L = (H(2)O)(2), n = 6] and their dinuclear homologues {[Ru(2)(trpy)(2)(L)](μ-bpp-bz)}(n+) [L = Cl or OAc, n = 2; L = (H(2)O)(2), n = 3] have also been prepared and thoroughly characterized both in solution and in the solid state. In solution, all of the complexes have been characterized spectroscopically by UV-vis and NMR and their redox properties investigated by means of cyclic voltammetry techniques. In the solid state, monocrystal X-ray diffraction analysis has been carried out for two dinuclear complexes {[Ru(2)(trpy)(2)(L)](μ-bpp-bz)}(2+) (L = Cl and OAc) and for the tetranuclear complex {[Ru(2)(trpy)(2)(μ-OAc)](2)(μ-(bpp)(2)-m-xyl)}(4+). The capacity of the tetranuclear aqua complexes {[Ru(2)(trpy)(2)(H(2)O)(2)](2)(μ-(bpp)(2)-u-xyl)}(6+) and the dinuclear homologue {[Ru(2)(trpy)(2)(H(2)O)(2)](μ-bpp-bz)}(3+) to act as water-oxidation catalysts has been evaluated using cerium(IV) as the chemical oxidant in pH = 1.0 triflic acid solutions. It is found that these complexes, besides generating significant amounts of dioxygen, also generate carbon dioxide. The relative ratio of [O(2)]/[CO(2)] is dependent not only on para, meta, or ortho substitution of the xylylic group but also on the concentration of the starting materials. With regard to the tetranuclear complexes, the one that contains the more sterically constrained ortho-substituted ligand generates the highest [O(2)]/[CO(2)] ratio.

Anticancer activity of tetracationic arene ruthenium metalla-cycles

A series of cationic metalla-cycles of the general formulae [(η(6)-p-cym)(4)Ru(4)(OO∩OO)(2)(N∩N)(2)](4+) and [(η(6)-p-cym)(4)Ru(4)(NO∩NO)(2)(N∩N)(2)](4+) has been prepared from the dinuclear arene ruthenium precursors [(η(6)-p-cym)(2)Ru(2)(OO∩OO)(2)Cl(2)] (OO∩OO = oxalato, 1,4-benzoquinonato-2,5-diolato, 1,4-naphtoquinonato-5,8-diolato, 9,10-anthraquinonato-1,4-diolato, 5,12-tetraquinonato-6,11-diolato) and [(η(6)-p-cym)(2)Ru(2)(NO∩NO)(2)Cl(2)] (NO∩NO = oxamido, oxonico) by reaction with two different bidentate linkers (N∩N = 1,2-bis(4-pyridyl)ethylene, 1,2-bis(4-pyridyl)ethane) in the presence of silver triflate. All complexes were isolated as triflate salts and characterised by NMR, infrared, UV-visible, mass spectrometry and by elemental analysis. The cytotoxicities of the tetranuclear ruthenium complexes have been established using ovarian A2780 and A2780cisR cancer cell lines. All complexes exhibit moderate to excellent activity on both the cisplatin resistant and cisplatin sensitive cells, thus suggesting a mode of action different from cisplatin.

Diruthenium(I,I) saccharinate complexes: Synthesis, molecular structure, and evaluation as catalysts for carbenoid reactions of diazoacetates

The dinuclear ruthenium complexes [Ru 2(μ-sac) 2(CO) 6] ( 1), [Ru 2(μ-sac) 2(CH 3CN) 2(CO) 4] ( 3), [Ru 2(μ-sac) 2(CO) 5(PPh 3)] ( 4) and [Ru 2(μ-sac) 2(CO) 4(PPh 3) 2] ( 5) as well as the tetranuclear ruthenium complex [Ru 2(μ-sac) 2(CO) 5] 2 ( 2) (sac = saccharinate, C 7H 4NO 3S −) were synthesized starting from Ru 3(CO) 12 and saccharin. X-ray crystal structure analysis of 1, 3A × p-xylene, 4 × CH 2Cl 2 and 5 × 3CH 2Cl 2 showed that the Ru 2 2 + core is bridged through the amidate moieties of the two saccharinate ligands, with a head–tail arrangement in complexes 1, 3A and 5, and a head–head arrangement in 4. For complex 3, an equilibrium mixture of the head–head regioisomer 3A and a second species 3b exists in solution. Complexes 1 and 2 are suitable catalysts for the cyclopropanation of nucleophilic alkenes (styrene, cyclohexene and 2-methyl-2-butene) with methyl diazoacetate.

Multimetallic Activation of Molecular Hydrogen, Leading to Hydrogenation of the Coordinated Azulenes in Di-, Tri-, and Tetranuclear Ruthenium Carbonyl Complexes

Abstract Hydrogenation of di-, tri-, and tetranuclear ruthenium carbonyl complexes bearing guaiazulene or 4,6,8-trimethylazulene as the bridging ligand to bind the multimetallic framework was studied: [μ2 : η-guaiazulene)Ru2(CO)5 (1a)], [μ2 : η-4,6,8-trimethylazulene)Ru2(CO)5 (1b)], [(μ3 : η-guaiazulene)Ru3(CO)7 (2a)], [(μ3 : η-4,6,8-trimethylazulene)Ru3(CO)7 (2b)], [(μ3 : η-guaiazulene)Ru4(CO)9 (3a)], and [(μ3 : η-4,6,8-trimethylazulene)Ru4(CO)9 (3b)]. Reactions of these di-, tri-, and tetraruthenium complexes with dihydrogen (PH2 = 5—10 atm) at 100 °C resulted in cluster fragmentation and addition of five hydrogen atoms to the azulene ligands to form mononuclear ruthenium carbonyl hydride compounds, [(η5-pentahydroguaiazulenyl)RuH(CO)2 (4a)] or [(η5-pentahydrotrimethylazulenyl)RuH(CO)2 (4b)]. Despite potential formation of several stereoisomers dependent on the addition modes of hydrogen atoms, only one isomer of 4a or 4b was obtained in the hydrogenation. The crystal structure of a derivative of 4a revealed that the addition of hydrogen atoms occurred from the face of the azulene ligand originally bonded with the ruthenium species. Hydrogenation of the di-, tri-, and tetranuclear ruthenium complexes below 100 °C revealed that only the triruthenium compounds reacted with H2 at 50 °C via triruthenium dihydride intermediates: [(μ2: η-tetrahydroguaiazulene)Ru3H2(CO)7 (6a)] or [(μ2: η-tetrahydrotrimethylazulene)Ru3H2(CO)7 (6b)]; this indicates that there exists a reaction pathway to achieve facile activation of dihydrogen by the triruthenium clusters.

Tetranuclear Tetrapyrido[3,2-a:2',3'-c:3",2"-h:2"',3"'-j]phenazineruthenium Complex: Synthesis, Wide-Angle X-ray Scattering, and Photophysical Studies.

The tetranuclear ruthenium complex {Ru[(tpphz)Ru(bpy)(2)](3)}(8+), where tpphz is tetrapyrido[3,2-a:2',3'-c:3",2"-h:2"',3"'-j]phenazine, has been synthesized by reaction of [Ru(tpphz)(3)](2+) with [Ru(bpy)(2)Cl(2)] and by reaction of [Ru(bpy)(2)(tpphz)](2+) with [Ru(DMSO)(4)Cl(2)]. The large distance between the chiral centers allows full (1)H NMR interpretation despite the mixture of eight stereoisomers. The tetranuclear complex was further characterized by electrospray mass spectrometry and by the wide-angle X-ray scattering technique, which confirmed the starburst geometry. The photophysical properties of the tetranuclear complex in acetonitrile were studied and compared with those of [Ru(tpphz)(3)](2+) (1 x 10(-)(4) M acidic solution) and [(bpy)(2)Ru(tpphz)Ru(bpy)(2)](4+) model molecules. The tetranuclear complex gives rise to a single emission, attributed to metal-to-ligand charge-transfer states involving peripheral Ru centers and tpphz bridging ligands.

Configurational stabilization of mixed-valence states in the star-burst tetranuclear ruthenium complex bridged with acetylene links

A new tetranuclear ruthenium complex in which a metal was bridged radially to three identical metals with acetylene links showed a mixed-valence state in cyclic voltammograms. The peak potential difference for the mixed-valence state was twice the potential difference for a mixed-valence state of the corresponding binuclear complex. This fact suggests stabilization of the mixed-valence state twice by configurational modification of redox centers. However, this is inconsistent with the prediction from the additive pair model of the redox interaction. A quantum chemical model of the redox interaction was presented, in which the potential difference was expressed by the overlap integral S and the nearest neighbor interaction energy between the reduced center and the oxidized one. Application of the theory gave a negative value of S, which demonstrated reasonably the stabilization of the mixed-valence state from a quantum chemical viewpoint.

Two new tetranuclear ruthenium complexes: [Ru2(CO)5(PPh2)(C2PPh2)]2 with two dinuclear units linked by two phosphinoacetylide bridges and [Ru4(CO)10(PPh)(PhC2PPh2)], a flattened butterfly with a .sigma.-.pi.-phenyl(diphenylphosphino)ethyne and a .mu.4-phosphinidene extracted from the bis(diphenylphosphino)ethyne reactant

Two new tetranuclear ruthenium complexes: [Ru2(CO)5(PPh2)(C2PPh2)]2 with two dinuclear units linked by two phosphinoacetylide bridges and [Ru4(CO)10(PPh)(PhC2PPh2)], a flattened butterfly with a .sigma.-.pi.-phenyl(diphenylphosphino)ethyne and a .mu.4-phosphinidene extracted from the bis(diphenylphosphino)ethyne reactant