Tetranuclear Ruthenium Research Articles

Trinuclear and Tetranuclear Ruthenium Carbonyl Nitrosyls: Oxidation of a Carbonyl Ligand by an Adjacent Nitrosyl Ligand.

Trinuclear and tetranuclear ruthenium carbonyls of the types Ru3(CO)n(NO)2, Ru3(N)(CO)n(NO), Ru3(N)2(CO)n, Ru3(N)(CO)n(NCO), Ru3(CO)n(NCO)(NO), Ru4(N)(CO)n(NO), Ru4(N)(CO)n(NCO), and Ru4(N)2(CO)n related to species observed experimentally in the chemistry of Ru3(CO)10(µ-NO)2 have been investigated using density functional theory. In all cases, the experimentally observed structures have been found to be low-energy structures. The low-energy trinuclear structures typically have a central strongly bent Ru-Ru-Ru chain with terminal CO groups and bridging nitrosyl, isocyanate, and/or nitride ligands across the end of the chain. The low-energy tetranuclear structures typically have a central Ru4N unit with terminal CO groups and a non-bonded pair of ruthenium atoms bridged by a nitrosyl or isocyanate group.

Pyridine and bipyridine complexes of tri- and tetranuclear ruthenium clusters revisited. Substitution, orthometallation and bridges between cluster units

The reactions of pyridine and 2-, 3- and 4-picoline with [H4Ru4(CO)12] were carried out under several experimental conditions and produced mono- and disubstituted products as well as complexes where Ru-Ru cleavage occurred, and orthometalation of the heterocycle took place. The disubstituted compound [(μ-H)4Ru4(CO)10(py)2] shows that both pyridine rings are coordinated to the same ruthenium atom; the 4-picoline also forms a similar complex. The reaction of [Ru3(CO)12] with 4,4´-bipyridine was also carried out. The product formed shows a bridged structure with both pyridine rings coordinated to a ruthenium triangle in an ortho-metalated mode. Spectroscopic characterization of all new compounds is described and the X-ray crystal structures of [(μ-H)4Ru4(CO)11py], [(μ-H)4Ru4(CO)10(py)2], [(μ-H)2Ru3(CO)8((μ-η2-NC5H4)2] and [{Ru3(CO)10}2(μ-η2–4,4´-(NC5H3)2] are described.

Revisiting the reactivity of Ru3(CO)12 with PhC≡CPh (diphenylacetylene)‒new findings of a thermic effect towards higher nuclearity

In this paper we report tri- and tetranuclear ruthenium carbonyl compounds containing PhC≡CPh ligand showing μ3-η2, μ3-η4, μ4-η2 coordination modes. A one-pot reaction between [Ru3(CO)12] and PhC≡CPh in THF (tetrahydrofuran) at 66 °C gave the new trinuclear compound [Ru3(CO)6(μ-CO)2(μ3-η4-C4Ph4)] (2) in 30% yield together with the previously reported [Ru3(CO)8(μ3-η2-C2Ph2)2] (1) in 25% yield. Compound 1 converts to 2 under refluxing condition in THF. A similar reaction involving [Ru3(CO)12] with PhC≡CPh in refluxing benzene (80 °C) afforded previously reported closo-tetraruthenium compounds [Ru4(CO)12(μ4-η2-C2Ph2)] (3) and [Ru4(CO)10(μ-CO)(μ4-η2-C2Ph2)2] (4) in 25 and 16% yields, respectively along with 2 in 20% yields. Compounds 1, 2 and 4 were characterized by single-crystal X-ray diffraction analysis in addition to IR and 1H NMR spectroscopic methods.

Tetranuclear ruthenium clusters anchored on polyoxometalates catalyze the hydrogenation of methyl levulinate in water

The tungstoaluminate-anchored ruthenium cluster catalyst is efficient and recyclable for the selective hydrogenation of methyl levulinate (ML) to gamma-valerolactone or methyl 4-hydroxypentanoate.

Novel tetranuclear ruthenium(II) arene complexes showing potent cytotoxic and antimetastatic activity as well as low toxicity in vivo

Ruthenium complexes have attracted a surge of interest as anticancer drug candidates because of their low toxicity, diversity in mode-of-actions and non-cross drug resistance with conventional platinum-based agents. Despite remarkable advances, only a limited number of ruthenium complexes have been demonstrated to kill cancer cells and suppress metastasis simultaneously. Here, two organometallic tetranuclear Ru(II) arene complexes (Ru-1 and Ru-2) have been synthesized and evaluated for their in vitro activity against a panel of human cancer cell lines, including a cisplatin-resistant human lung cancer A549 cell line. A superior cytotoxic activity of the ruthenium complexes compared to cisplatin across distinct cell lines was observed. Further examination of the mechanism indicated that anticancer activity was accomplished by inducing apoptosis in cancer cells. In addition, we found that such compounds exhibited promising antimetastatic activity and reduced the invasiveness of cancer cells. Importantly, choosing Ru-1 as a target compound, a significantly enhanced safety profile relative to cisplatin in animals was validated, suggesting that these complexes can be used as promising candidates for cancer therapy and deserve further investigation.

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.

Flexible ligated ruthenium(II) self-assemblies sensitizes glioma tumor initiating cells in vitro.

The tumorigenic potentials of residual cancer stem-like cells within tumors represent limitations of current cancer therapies. Here, the authors describe the effects of synthesized flexible, ligated, supramolecular self-assembled chair type tetranuclear ruthenium (II) metallacycles (2–5) on glioblastoma and glioma stem like cells. These self-assemblies were observed to be selectively toxic to glioma cells and CD133-positive glioma stem like cells population. Of the self-assembled compounds tested, metallacycle 4 more efficiently induced glioma stem like cells death within a brain cancer cell population and simultaneously inhibited the formation of free-floating gliospheres by reducing the sphere size. Detailed cell death studies revealed that treatment with metallacycle 4 reduced mitochondrial membrane potentials (an indicator of apoptosis) of glioma stem like cells. These results shows the elimination of cancer stem-like cells using an appropriate ligand binding adaptor offers a potential means of developing metal-based compounds for the treatment of chemo-resistant tumors.

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).

Reactivity of dirhenium and triruthenium carbonyls toward a biphosphole ligand: M–M, P–P and C–H bonds cleavage

The reaction of [Re2(CO)8(CH3CN)2] with bis(2-thienyl)biphosphole in refluxing n-octane affords the complex [Re(CO)3(η5-PC16H14S2)] (1) where cleavage of the Re–Re and P–P bonds occurs; its molecular structure confirms the formation of a rhenium mononuclear compound with a η5-coordinated phospholyl unit and three carbonyl groups oriented in a tripod. On the other hand, bis(2-thienyl)biphosphole reacts with [Ru3(CO)12] in refluxing cyclohexane to affording two new compounds [Ru3(CO)9(μ:η1:η5-PC16H13S2)] (2) and [Ru4(CO)13(μ:η1-PC16H14S2)2] (3). Spectroscopic data and theoretical studies of 2 suggest the formation of an open Ru3 cluster with two metal–metal bonds bridged by a (η1:η5-PC16H13S2) unit and a C-H bond activation of one of the thienyl substituents. X-ray structure of 3 reveals a novel tetranuclear ruthenium cluster containing 13 terminal carbonyl ligands and two phospholyl units coordinated as μ-phosphide.

Recent Advances in Small Clusters and Polymetallic Assemblies Based on Transition Metals and Dithiocarboxylate Zwitterions Derived from N-Heterocyclic Carbenes

N-Heterocyclic carbenes (NHCs) react readily with carbon disulfide to form stable, crystalline, zwitterionic adducts. In this review, we outline the various strategies that were applied to synthesize transition metal clusters based on such NHC·CS2 ligands. We also briefly survey their most salient structural features and catalytic properties. Because this research field is still in its infancy, only a limited number of structures containing metals from Group 7 (Mn and Re) and 8 (Fe and Ru) have been described so far. Homo- and heterobimetallic manganese and rhenium carbonyl clusters with the generic formula [MM′(CO)6(μ-κ2-S,S′-κ3-S,C,S′-S2C·NHC)] (MM′ = Mn2, MnRe, or Re2) were most thoroughly investigated. Isolated examples of dinuclear iron and tetranuclear ruthenium compounds, in which the dithiocarboxylate unit underwent fragmentation, were also reported. Other related polymetallic entities recently elaborated through the use of azolium-2-dithiocarboxylate zwitterions and Group 11 metals (Cu and Au) include copper-based coordination polymers, gold nanoparticles, and self-assembled monolayers.

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.

Synthesis and characterisation of tetranuclear ruthenium polyhydrido clusters with pseudo-tetrahedral geometry.

Dicationic tetranuclear ruthenium octahydride [(Cp*Ru)4H8]2+ (5) with tetrahedral geometry was obtained by reaction of dinuclear ruthenium tetrahydride (Cp*Ru)2(μ-H)4 (1) with an excess of Brønsted acids, such as HBF4·OEt2, in toluene. Monocationic tetraruthenium heptahydride [(Cp*Ru)4H7]+ (7) was obtained by dropwise addition of a diluted acid to a rigorously stirred solution of 1 at ambient temperature. Dication 5 was converted into monocationic heptahydrido complex 7 in high yield by treatment with sodium methoxide or sodium hydride. The direct conversion of 5 into neutral hexahydrido complex (Cp*Ru)4H6 (8) was achieved in a highly efficient manner by treating 5 with LiAlH4 in tetrahydrofuran (THF). The conversion of 5 into 8 was reversible, and the addition of a Brønsted acid to 8 gave 5via the formation of 7 as an intermediate. Tetranuclear complex 8 was directly obtained from 1 by heating it in THF at 70 °C. Complex 8' and tetraruthenium tetrahydride (CpEtRu)4H4 (10'), where 8' and 10' possessed η5-C5EtMe4 ligands instead of Cp* ligands, were mutually related by the elimination/addition of dihydrogen. The structures of 5, 7, 8, and 10' were determined by X-ray diffraction, and the Ru4 core structure and the coordination mode of hydrido ligands were discussed based on density functional theory (DFT) calculations for model compounds where the methyl groups of Cp* ligands were replaced with hydrogen atoms.

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.

Synthesis of Tetranuclear Ruthenium (Ii) Complex of Pyridyloxy-Substituted 2,2′-Dioxybiphenyl-Cyclotriphosphazene Platform and its Catalytic Application in the Transfer Hydrogenation of Ketones

GRAPHICAL ABSTRACT

Lipophilic tetranuclear ruthenium(II) complexes as two-photon luminescent tracking non-viral gene vectors.

Fluorescence detection is the most effective tool for tracking gene delivery in living cells. To reduce photodamage and autofluorescence and to increase deep penetration into cells, choosing appropriate fluorophores that are capable of two-photon activation under irradiation in the NIR or IR regions is an effective approach. In this work, we have developed six tetranuclear ruthenium(II) complexes, GV1-6, and have studied their one- and two-photon luminescence properties. DNA interaction studies have demonstrated that GV2-6, bearing hydrophobic alkyl ether chains, show more efficient DNA condensing ability but lower DNA binding constants than GV1. However, the hydrophobic alkyl ether chains also enhance the DNA delivery ability of GV2-6 compared with that of GV1. More importantly, we have applied GV1-6 as non-viral gene vectors for tracking DNA delivery in living cells by one- and two-photon fluorescence microscopies. In two-photon microscopy, a high signal-to-noise contrast was achieved by irradiation with an 830 nm laser. This is the first example of the use of transition-metal complexes for two-photon luminescent tracking of the cellular pathways of gene delivery and as DNA carriers. Our work provides new insights into improving real-time tracking during gene delivery and transfection as well as important information for the design of multifunctional non-viral vectors.

Tetranuclear ruthenium(II) complexes with oligo-oxyethylene linkers as one- and two-photon luminescent tracking non-viral gene vectors.

To prolong the observation time, increase the penetration depth and decrease self-absorption and phototoxicity, two-photon luminescent vectors have emerged as promising tools for tracking gene delivery in living cells. Herein, we report four new tetranuclear Ru(ii) complexes based on oligo-oxyethylene and polybenzimidazole as one- and two- photon luminescent tracking non-viral gene vectors. In such a molecular design, the oligo-oxyethylene, polybenzimidazole and Ru(ii) polypyridyl complexes were expected to render the vectors with increased cell permeability, biocompatibility, proton buffering capacity and one- and two-photon luminescence. Corresponding DNA interaction studies showed that the ability of the complexes to condense DNA decreased with increasing oligo-oxyethylene lengths. Additionally, all complexes protected DNA. The complexes were investigated as one- and two-photon tracking non-viral gene vectors in living cells and showed proper cellular uptake, good luciferase expression and low cytotoxicity.

Tetranuclear ruthenium(II) complex with a dinucleating ligand forming multi-mixed-valence states.

A square-shaped tetranuclear ruthenium(II) complex, [Ru(II)4Cl5(bpmpm)2](3+) [1; bpmpm = 4,6-bis[[N,N-bis(2'-pyridylmethyl)amino]methyl]pyrimidine], exhibited four reversible and stepwise one-electron-oxidation processes: chemical oxidation of 1 formed three different mixed-valence states, in one of which the charge is partially delocalized on the two Ru centers, to be evidenced by observation of an intervalence charge-transfer absorption band, categorized into the Robin-Day class II.

Synthesis, characterization, and reactivity of self-assembled tetranuclear arene ruthenium metalla-rectangles

Self-assembly of 4,4′-bipyridine (bpy) with arene-ruthenium building blocks and 2,2′-bisbenzimidazole (H2BiBzIm) in the presence of AgOTf (OTf = OSO2CF3) afforded tetranuclear cations of the type [Ru4(η6-arene)4(bpy)2(BiBzIm)2]4+ (arene = p-iPrC6H4Me 1, C6Me6 2), while similar reactions by use of [(η6-C6Me6)Ru(μ-Cl)Cl]2 and excess AgOTf led to isolation of a cationic coordination network {[Ru4(η6-C6Me6)4(bpy)2(BiBzIm)2·Ag2(OTf)4]2+}n (3), which could also be obtained by treatment of [2][OTf]4 with AgOTf in methanol. Complex 3 is constructed by π coordination of BiBzIm(η2-carcon) with Ag(I). The coordination geometry around the silver(I) ion is pseudo-tetrahedral (taking the C=C group as one ligand). Self-assembly of only two components: [(η6-C6Me6)Ru(μ-Cl)Cl]2 reacted with the 3-pyridyl-bian (mPy-bian) linker in the presence of limited AgOTf to give a chloro-bridged metalla-rectangle [Ru4(η6-C6Me6)4(μ-Cl)4(mPy-bian)2Ag]5+ (4), which enclosed a silver in the center. The coordination geometry around silver(I) in 4 is unusual square planar. The molecular structures of 1–4 were confirmed by X-ray crystallography along with other spectroscopic properties.

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.

Ru4(CO)8(μ-OOCCH2CH3)4(THF)2] and [Ru3(μ3-OH)(CO)6(μ-OOCtBu)4(OOCtBu)]: Novel Multinuclear Ruthenium Carbonyl Carboxylates

The reaction of Ru3(CO)12 with pivalic or propionic acid leads to the formation of two novel multinuclear ruthenium complexes, [Ru4(CO)8(μ-OOCCH2CH3)4(THF)2] (1) and [Ru3(μ3-OH)(CO)6(μ-OOCtBu)4(OOCtBu)] (2). Compound 1 is among the few examples of discrete tetranuclear ruthenium compounds showcasing a “dimer of dimers” paddlewheel structure, in which two “Ru2(CO)4(μ-OOCCH2CH3)2(THF)” fragments are linked via Ru–O interactions. Compound 2 features a unique structural motif in which a triangular Ru3 core is connected via a μ3-OH ligand.