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• Detail study of (η6-C 6 Me 6)Ru(Cl) 2 (P(OMe) 3) with AgOTf in different solvents. • A comparative study of counterions OTf− and BF 4 −in [(η6-C 6 Me 6)Ru(Cl)(P(OMe) 3) 2 ]X. • Formation of mono-, di- and trinuclear structures with (η6-C 6 Me 6)Ru(P(OMe) 3) moieties. • Complex sequence which undergoes coordinated trimethylphosphite ligands in solution. • A great preference to coordinate adventitious water and labile acetone adducts. An extensive study of the reactions of (η6-C 6 Me 6)Ru(Cl) 2 (P(OMe) 3) (1) with AgOTf in three different deuterated and non-deuterated solvents: chloroform, acetone and nitromethane is described. A series of compounds with the moiety (η6-C 6 Me 6)Ru(P(OMe) 3) is isolated and characterized, along with their crystalline structures. A simple associative step assisted by coordination of the silver cation to two molecules of 1 through the Cl-Ru-Cl bonds affords [{(η6-C 6 Me 6)Ru(Cl) 2 (P(OMe) 3)} 2 (μ-Ag)](OTf) (2), loss of AgCl from 2 gives 1 and (η6-C 6 Me 6)RuCl(OTf)(P(OMe) 3) (3), meanwhile 3 dimerizes to [(η6-C 6 Me 6)Ru(μ-Cl)(P(OMe) 3)] 2 (OTf) 2 (4) which in presence of P(OMe) 3 gives [(η6-C 6 Me 6)RuCl(P(OMe) 3) 2 ](OTf) (11OTf). A comparative study of the influence of the counterions OTf− and BF 4 − was carried out with the analogue [(η6-C 6 Me 6)RuCl(P(OMe) 3) 2 ](BF 4) (11BF4), as well as the corresponding demethylation of the coordinated trimethylphosphite ligands by the classical Michaelis-Arbuzov reactions. The resulting "quasi-chelate" (η6-C 6 Me 6)RuCl(P(O)(OMe) 2)(P(OH)(OMe) 2) (17) where a bridging proton in the phosphinito-phosphinous acid ligands is replaced by BF 2 affords (η6 - C 6 Me 6)RuCl({P(OMe) 2 (O)} 2 BF 2) (18) which contains the chelating structure [Me 2 POBF 2 OPMe 2 ]. The chemistry in solution at room temperature of 1 with AgOTf shows non-selective reactions, as can be determined by multinuclear NMR spectroscopy (1H, 13C{1H}, 31P, 19F). The mixture of products shows a great preference to coordinate water, even when it is in traces, as observed for the formation of [(η6-C 6 Me 6)RuCl(H 2 O)(P(OMe) 3)](OTf) (5), [(η6-C 6 Me 6)Ru(H 2 O)(OTf)(P(OMe) 3)]OTf (6) and [(η6-C 6 Me 6)Ru(H 2 O) 2 (P(OMe) 3)](OTf) 2 (7), being the latter 7 the "sink" product. Also, in presence of anhydrous AgOTf compound 1 can be transformed into the highly hygroscopic (η6-C 6 Me 6)Ru(OTf) 2 (P(OMe) 3) (8) which readily replaces triflate ligands by trace water. Structural characterization by single crystal X-ray diffraction of trinuclear compound 2 , dinuclear 4 and mononuclear 7, 11X (X = OTf, BF4), 18 and nitrile derivatives [(η6-C 6 Me 6)Ru(NCR) 2 (P(OMe) 3)](OTf) 2 (R = Et, 9 ; Me, 10) is discussed. The chemical transformations of AgOTf with (η6-C 6 Me 6)Ru(Cl) 2 (P(OMe) 3) lead to a variety of organoruthenium compounds in a non-selective path. The competition between products depends on the stoichiometry, solvent, and largely on the silver triflate salt, whose hygroscopic capacity favors the coordination of water in several compounds under study. [Display omitted] [ABSTRACT FROM AUTHOR]

In recent years, extensive research efforts have been focused on loading metal complexes onto macromolecular systems such as nanoparticles. We report a ligand with a catechol group based on a picolinamide which allows for coordination to organoruthenium moieties while the catechol group remains available for loading on nanoparticles as delivery vehicles towards tumors. All the compounds were characterized with standard analytical methods and the molecular structure of the ligand 1 , and its Ru complexes 1a and 1b were determined by X-ray diffraction analysis. The crystal structure of 1a and 1b showed pseudo-tetrahedral geometry of the Ru center with "piano-stool" conformation and 1 coordinated as an N,O -bidentate ligand, however, the latter depending on the reaction conditions employed. The Ru complexes 1a – 1c were effectively loaded on magnetite nanoparticles as characterized by inductively-coupled plasma mass spectrometry (ICP-MS), transmission electron microscopy (TEM) and Fourier transform infrared spectroscopy (FTIR). The functionalization of a picolinamide-derived ligand with a catechol group led to organoruthenium compounds that could be loaded on iron oxide nanoparticles. Nanoparticle modification was characterized by inductively-coupled plasma mass spectrometry, transmission electron microscopy and Fourier transform infrared spectroscopy. Image 1 • Design of organometallic compounds for nanoparticle functionalization. • Preparation of organometallic compounds and characterization. • Loading of the organometallic compounds to the nanoparticles. • Characterization of the nanoparticles by TEM, ICP-MS and FTIR. [ABSTRACT FROM AUTHOR]

The open-shell density functional theory calculations with M06 exchange-correlation functional and all-electron Douglas-Kroll second order scalar relativistic correction were performed to interpret the vibrational circular dichroism (VCD) spectra of four kinds of tris(acetylacetonato)metal(III), [M(III)(acac)3] (acac = acetylacetonato, M = Ru, Cr, Co, and Rh). It was deduced that the experimental spectra were well reproduced by the calculation with harmonic approximation in case of [Co(III)(acac)3] (d6; S = 0), [Rh(III)(acac)3] (d6; S = 0), and [Ru(III)(acac)3] (d5; S = 1/2). In case of [Cr(III)(acac)3] (d3; S = 3/2), anharmonic effects should be taken into account to predict the accurate vibrational frequencies of closely located modes. Time-dependent density functional theory calculations were performed to estimate the contribution of excited states in the VCD spectra. As a consequence, the presence of the low-lying excited states was predicted for [Ru(III)(acac)3] alone, which agreed with the experimental observation. [ABSTRACT FROM AUTHOR]

We report on lighting panels based on ruthenium(II) tris-bipyridine complexes that can be sourced directly from a standard US outlet. With the aid of the ionic liquid 1-butyl-3-methylimidazolium, the conductivity of the light emitting layer was enhanced to achieve device operation at a 60 Hz frequency. Lighting panels were prepared using a cascaded architecture of several electroluminescent devices. This architecture sustains high input voltages, provides fault tolerance, and facilitates the fabrication of large area solid-state lighting panels. Scalability of the drive voltage, radiant flux, and external quantum efficiency is demonstrated for panels with up to N=36 devices. Direct outlet operation is achieved for panels with N=16, 24, and 36 devices. [ABSTRACT FROM AUTHOR]

In order to address outstanding questions about ruthenium complexes in complex biological solutions, 19F NMR spectroscopy was used to follow the binding preferences between fluorinated RuII(η6-arene)(bipyridine) complexes and protected amino acids and glutathione. Reporting what ruthenium compounds bind to in complex environments has so far been restricted to relatively qualitative methods, such as mass spectrometry and X-ray spectroscopic methods; however, quantitative information on the species present in the solution phase cannot be inferred from these techniques. Furthermore, using 1H NMR, in water, to distinguish and monitor a number of different complex RuII(η6-arene) adducts forming is challenging. Incorporating an NMR active heteroatom into ruthenium organometallic complexes provides a quantitative, diagnostic 'fingerprint' to track solution-phase behaviour and allow for unambiguous assignment of any given adduct. The resulting 19F NMR spectra show for the first time the varied, dynamic behaviour of organoruthenium compounds when exposed to simple biomolecules in complex mixtures. The rates of formation of the different observed species are dramatically influenced by the electronic properties at the metal, even in a closely related series of complexes in which only the electron-donating properties of the arene ligand are altered. Preference for cysteine binding is absolute: the first quantitative solution-phase evidence of such behaviour. [ABSTRACT FROM AUTHOR]

Benzoylthiourea derivatives feature several donor atoms capable of coordinating to metal centers. We report here a series of Ru(η6‐p‐cymene) complexes employing benzoylthiourea derivatives as ligands. Such ligands often coordinate to metal centers through their S and O donor atoms. We isolated complexes where the ligands were mono‐ or bidentately coordinated to Ru involving the S donor atom and surprisingly in bidentate coordination mode a deprotonated thiourea nitrogen resulting in a 4‐membered ring structure around the metal center. DFT calculations were used to explain the differences in coordination behavior. These were complemented by stability studies and biological investigations of the compounds as anticancer agents. Several of the synthesized derivatives exhibited significant cell growth inhibitory activity, with the complexes featuring bidentate ligands being more potent than their monodentate counterparts. This can be explained by the higher stability of the former under the conditions employed in cell culture assays. [ABSTRACT FROM AUTHOR]

Abstract: Three new ruthenium(II)-arene complexes with pyrido[2′,3′:5,6]pyrazino[2,3-f][1, 10]phenanthroline (ppf) of general formula: C1 ([(ƞ6-benzene)Ru(ppf)Cl]PF6, C2 ([(ƞ6-toluene)Ru(ppf)Cl]PF6) and C3 ([(ƞ6-p-cymene)Ru(ppf)Cl]PF6) have been synthesized. The structures of complexes were determined by elemental analysis, IR, ESI-MS, as well as with 1H and 13C NMR spectroscopy. Cytotoxic activity has been evaluated in three different human neoplastic cell lines (A549, A375, LS 174T) and in one human non-tumor cell line (MRC-5), by the MTT assay. Complexes C1-C3 showed IC50 values in the micromolar range below 100 µM. Complex C3, carrying ƞ6-p-cymene as the arene ligand, exhibited cytoselective activity toward human malignant melanoma A375 cells (IC50 = 15.8 ± 2.7 µM), and has been selected for further analyses of its biological effects. Drug-accumulation study performed in the A375 cells disclosed that C3 possess lower ability of entering the cells compared to cisplatin and distributes approximately equally in the cytosol and membrane/organelle fraction of cells. Investigations in the 3D model of A375 cells, disclosed different effects of the complex C3 and cisplatin on growth of multicellular tumor spheroids (MCTSs). While the size of cisplatin-treated MCTSs decreased with time, MCTSs treated with C3 continued to growth. Differences in structural organization and biological activity of this type of ruthenium(II)-arene complexes versus cisplatin in A375 malignant melanoma cells pointed out their different modes of action, and necessity for further biological studies and optimizations for potential applications.Graphical abstract: [ABSTRACT FROM AUTHOR]

In this article, Ru(ii)–arene-2-pyridinylbenzoxazole complexes [(η6-p-cymene)RuCl(κ2-N,N-5-bromo-2-(pyridine-2-yl)benzo[d]oxazole)] (4) and [(η6-benzene)RuCl(κ2-N,N-5-bromo-2-(pyridine-2-yl)benzo[d]oxazole)] (5) and Ru(ii)–arene-2-quinolylbenzoxazole complexes [(η6-p-cymene)RuCl(κ2-N,N-5-bromo-2-(quinoline-2-yl)benzo[d]oxazole)] (4′) and [(η6-benzene)RuCl(κ2-N,N-5-bromo-2-(quinoline-2-yl)benzo[d]oxazole)] (5′) were synthesized and characterized using various spectroscopic techniques. Structural analysis indicates that the Ru(ii) centres are in a distinct mononuclear, one-sided octahedral [RuN6] coordination geometry with two neutral bidentate nitrogen donors in the bromobenzoxazole ligands. All four complexes exhibit three different electronic bands: a sharp band at 300–330 nm due to ligand-to-ligand charge transfer (LLCT); a band around 400 nm due to metal-to-ligand charge transfer; and a small broad peak at around 600 nm due to ligand-to-metal charge transfer. The fluorescence abilities of the four complexes were studied using the LLCT absorption peak as the excitation energy in dimethylsulfoxide: water (1 : 1, v/v), and the quantum yield was found to decrease in the order of 5′ ＞ 4′ ＞ 4 ＞ 5. Density functional theory calculations reveal that the highest-occupied molecular orbital is primarily located on the benzoxazole ring system, while the lowest-unoccupied molecular orbital is mainly located on the Ru atom, which implies possible charge transfer from ligand to metal. The binding strengths of the Ru(ii) complexes with DNA (5′ ＞ 4′ ＞ 4 ＞ 5) and bovine serum albumin (4′ ＞ 5′ ＞ 5 ＞ 4) were on the order of 105–106 and 103–105 M−1, respectively. The conductometric data reveal that all four complexes are non-electrolytic in nature, and viscosity decreases in the order of 5′ ＞ 4′ ＞ 4 ＞ 5. This might be due to the effective intercalation of 5′ compared to the other complexes. DNA and protein docking studies suggest that all the complexes interact with DNA through the minor groove and favourably occupy the active sites of proteins based on dipole–dipole interactions. Gel electrophoresis studies show that all complexes degrade plasmid DNA (1 kb) completely within 1 h of exposure time. MTT assay results indicate that all complexes exhibit highly selective cytotoxicity for two cancer cell lines (Caco-2 and HeLa) with respect to normal HEK-293 cells. Among the complexes, 4′ and 5 show the highest cytoselectivities for the Caco-2 and HeLa cell lines, respectively. [ABSTRACT FROM AUTHOR]

In this work we report a new and simplified synthesis of ruthenocene that prevents the formation of unwanted by‐products. We have also revisited the vibrational spectroscopy of this iconic molecule and in addition to infrared and variable temperature Raman spectra, we present the first inelastic neutron scattering (INS) spectrum, a technique that is little used in inorganic chemistry. The Raman spectra in the low energy range (< 200 cm–1) clearly show that the mode assigned as the ring–Ru–ring torsion is a librational mode. By generating the INS spectra predicted by previous assignment schemes we are able to show that they are all, at least partially, wrong because they fail to correctly predict the experimental INS spectrum. In the case of ruthenocene, the addition of INS data, in combination with periodic‐DFT calculations, has enabled the first correct assignment of the internal modes of ruthenocene. This straightforward means to test proposed assignments is one of the great strengths of vibrational spectroscopy with neutrons. In this work we report a simplified synthesis of ruthenocene and the vibrational spectroscopy of this iconic molecule. The addition of inelastic neutron scattering data in combination with periodic‐DFT calculations has enabled the first correct assignment of the internal modes of ruthenocene. [ABSTRACT FROM AUTHOR]

Optimal control of gas adsorption properties in metal–organic frameworks (MOFs) or porous coordination polymers (PCPs) remains a great challenge in the field of materials science. An efficient strategy to capture electron‐acceptor‐type gas molecules such as nitrogen monooxide (NO) is to use host–guest interactions by utilizing electron‐donor‐type MOFs/PCPs as host frameworks. Herein, we focus on a highly electron‐donating chain compound by using the paddlewheel‐type [Ru2II,II] complex [Ru2(2,4,5‐Me3PhCO2)4] (2,4,5‐Me3PhCO2−=2,4,5‐trimethylbenzoate) with the phenazine (phz) linker: [Ru2(2,4,5‐Me3PhCO2)4(phz)] (1). Compound 1 exhibited a specific gated adsorption for NO under gas pressures greater than 60 kPa at 121 K, which finally resulted in approximately seven molar equivalents being taken up at 100 kPa followed by four molar equivalents remaining under vacuum at 121 K; its Rh isomorph (2) with weaker donation ability was inactive for NO. When the sample of 1⊃4 NO was heated to room temperature, the compound underwent a crystal‐to‐crystal phase transition to give [Ru2(2,4,5‐Me3PhCO2)4(NO)2](phz) (1‐NO), involving a post‐synthetic nitrosylation on the [Ru2] unit, accompanied by an eventful site‐exchange with phz. This drastic event, which is dependent on the NO pressure, temperature, and time, was coherently monitored by using several different in situ techniques, revealing that the stabilization of NO molecules in nanosized pores dynamically and stepwisely occurred with the support of strong electronic/magnetic host–guest interactions. In situ techniques: Selective NO capture in a Ru dimer chain porous compound through strong host–guest magnetic/electronic interactions was evaluated multilaterally by using in situ techniques of powder magnetic and permittivity measurements, IR spectroscopy, and X‐ray diffraction. A dynamic change with respect to the NO trapping in pores can be followed, which undergoes a crystal‐to‐crystal transformation from a gate‐opened NO adsorbed form to an NO‐adducted form. [ABSTRACT FROM AUTHOR]

While the fascinating chemistry demonstrated by metalated N‐heterocyclic carbene (NHC) complexes highlights the significance of metalated heterocyclic chemistry, the development of other metalated heterocycles is falling behind, presumably because of the sparseness of general synthetic methodologies. In this Concept article, the strategy to prepare metalated heterocyclic complexes by metal‐induced cycloisomerization of heteroatom‐functionalized alkynes is presented. The isolation of and calculations on novel ruthenium complexes bearing chromene, chromone, indole, indoline, indolizine, and indolizinone moieties prepared from reactions between alkynes and ruthenium complexes are discussed, with emphasis on the mechanistic insights into the ruthenium‐induced alkyne transformations and applications in material design and drug discovery. Metalated heterocycles: This Concept article highlights the recent progress of isolating metalated heterocyclic complexes by ruthenium‐mediated activation of heteroatom‐functionalized alkynes, with emphasis on mechanistic insights into the ruthenium‐induced alkyne transformations and applications in material design and drug discovery. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • New olefin-tethered organoruthenium carbene complexes have been synthesized and epitomized. • X-ray studies confirmed an octahedral geometry of the new complexes. • The newly synthesized complexes catalyze the hydrogenation of esters efficiently. Abstract A series of Ru(II) complexes encompassing imidazolylidene olefin arm have been designed. The newly synthesized ligands and complexes were fully characterized by 1H, 13C NMR, and elemental analyses. Structural geometry for one of the envoy Ru(II) carbene complexes 3a was confirmed by single-crystal X-ray diffraction studies. The complexes acquired a distorted octahedral geometry. The highly active [Ru(II)-NHC] complex 3b , showed excellent catalytic performance for the hydrogenation of esters in 1,4-dioxane medium. The effects of solvent, base, wingtip substituents, time and catalyst loading were also investigated. The reported catalyst performed exceptionally well for a range of esters and furnishes very good yield of hydrogenated products. [ABSTRACT FROM AUTHOR]

Four new organoruthenium complexes with formula [RuCl(η6-p-cymene)(μ-FCZ)]2[Cl]2 (1), [RuCl(FCZ)(η6-p-cymene)(PPh3)]PF6 (2), [RuCl(CTZ)(η6-p-cymene)(PPh3)]PF6 (3) and [RuCl(KTZ)(η6-p-cymene)(PPh3)]PF6 (4) (where FCZ: 2-(2,4-difluorophenyl)-1,3-di(1H-1,2,4-triazol-1-yl)-2-propanol, CTZ: 1-[(2-chlorophenyl)-diphenylmethyl-1H-imidazole] and KTZ: cis-1-acetyl-4-[4-[[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazine) were synthesized, characterized and evaluated as potential inhibitors for Leishmania amazonensis growth by widely reported methods. Complexes 3 and 4 displayed effective IC50 activities against Leishmania amazonensis promastigotes and intracellular amastigotes in the range of nanomolar concentration. Scanning and transmission electron microscopy analysis of Leishmania amazonensis promastigotes after treatment with 300 or 500 nM of complexes 3 and 4 for 48 h showed morphological alterations in the cell surface, a shortening of the flagellum, loss of mitochondrial matrix, disorganization of the kDNA and abnormal chromatin condensation. Thus, our strategy of incorporating a ruthenium atom into the structure of clinical drugs to improve their efficacy continues to demonstrate suitability for metallodrug discovery purposes. [ABSTRACT FROM AUTHOR]

Eleven ruthenium-nucleoside conjugates with the general formula [(η5-C5H5)Ru(PP)L][PF6] (PP = 1,2-bis(diphenylphosphino)ethane (Dppe), 2PPh3, and L = 3-N-(p-cyanobenzyl)thymidine derivative ligand) are reported. Both [(η5-C5H5)Ru(Dppe)N≡C-R]+ and [(η5-C5H5)Ru(PPh3)2N≡C-R]+ scaffolds exhibit remarkable stability towards hydrolysis. Compounds show high cytotoxicity in HCT116 colon cancer cells, with IC50 values down to 1.0 μM. Uptake competition experiments with 2′-deoxyadenosine revealed its cellular absorption to be independent of nucleoside transporters. [ABSTRACT FROM AUTHOR]

Nucleophilic attack on complex [RuCl(η6‐C10H14){κ3(P,C,C)‐Ph2PCH2CH=CH2}][BPh4] (2) takes place, either to the metal or to the coordinated olefin depending on the nucleophile and the reaction conditions. The nucleophilic attack of phosphanes on the coordinated olefin leads diastereoselectively to complexes [RuCl(η6‐C10H14){ĸ2(P,C)‐Ph2PCH2CH(PR3)CH2}]+ bearing κ2(P,C)‐ligands obtained as a racemic mixture of the enantiomers RRuSc/SRuRC. These kinetically stable isomers, undergo an isomerization process leading to the thermodynamically stable products isolated as the diastereoisomer RRuRC/SRuSC. 31P{1H} NMR monitoring experiments on the isomerization processes have been carried out. New Ru complexes containing bidentate κ2(P,C)‐ligands [RuCl(η6‐C10H14){ĸ2(P,C)‐Ph2PCH2CH(PR3)CH2}][BPh4] have been diastereoselectively synthesized as the kinetically stable isomer (RRuSC/SRuRC). This diastereoisomer spontaneously evolves to the thermodynamically stable diastereoisomer (RRuRC/SRuSC). 31P{1H} NMR monitoring experiments shed light on the isomerization processes. [ABSTRACT FROM AUTHOR]

In this study we report the synthesis, characterization and a thorough biological evaluation of twelve organoruthenium–8-hydroxyquinolinato ( Ru-hq ) complexes. The chosen hqH ligands bear various halogen atoms in different positions which enables to study effect of the substituents on physico-chemical and biological properties. The determined crystal structures of novel complexes expectedly show the cymene ring, a bidentately coordinated deprotonated hq and a halide ligand (chlorido or iodido) coordinated to the ruthenium central ion. In previous studies the anticancer potential of organoruthenium complex with 8-hydroxyquinoline ligand clioquinol was well established and we have decided to perform an extended biological evaluation (antibacterial and antitumor activity) of the whole series of halo-substituted analogs. Beside the cytotoxic potential of studied compounds also the effect of two selected complexes ( 9 and 10 ) on apoptosis induction in MG-63 and A549 cells was also studied via externalization of phosphatidylserine at the outer plasma membrane leaflet. Both selected complexes that gave best preliminary cytotoxicity results contain bromo substituted hq ligands. Apoptosis induction results are in agreement with the cell viability assays suggesting the higher and more selective anticancer activity of complex 10 in comparison to complex 9 on MG-63 cells. [ABSTRACT FROM AUTHOR]

Anticancer-active RuII-η6-p-cymene complexes of bioactive 2-pyridinecarbothioamide ligands have been shown to have high selectivity for plectin and can be administered orally. Reported herein is the functionalization of a 2-pyridinecarbothioamide with a sulfonamide group and its conversion into M-η6-p-cymene complexes (M = Ru, Os). The presence of a sulfonamide moiety in many organic drugs and metal complexes endows these agents with interesting biological properties and can transform the latter into multi-targeted agents. The compounds were characterized with standard methods and the in vitro anticancer activity data was compared with studies on the hydrolytic stability of the complexes and their reactivity to small biomolecules. A molecular modeling study revealed plausible modes of binding of the complexes in the catalytic pocket of carbonic anhydrase II. [ABSTRACT FROM AUTHOR]

A series of four new, cyclometallated ruthenium (II) complexes was synthesized from 3-acetyl-8-methoxy-2H-chromen-2-one functionalized 4( N )- substituted thiosemicarbazones and characterized through various spectral and analytical methods. The molecular structures of the complexes 1 , 2 and 4 were determined by single-crystal X-ray diffraction analysis, which confirmed that the complexes possess a distorted octahedral geometry with the ligands coordinating in a dibasic tridentate fashion via C, N and S atoms. DNA [Calf Thymus DNA (CT-DNA)] and protein [Bovine Serum Albumin (BSA) and Human Serum Albumin (HSA)] binding studies indicated an intercalative mode of binding with DNA and static quenching mechanism with proteins. The compounds cleaved plasmid DNA (pBR322) without application of any external agent and acted well as free radical scavengers. A good spectrum of antimicrobial activity was observed against four bacterial and five fungal pathogens. Two cancerous cell lines, MCF-7 (human breast cancer) and A549 (human lung carcinoma) were employed to test their in vitro cytotoxic activity using MTT assay. The complexes ( 1–4 ) showed better activity with lower IC 50 values over cisplatin . Further non toxic nature of the complexes have been examined with human normal keratinocyte cell line HaCaT. Further, the results of Lactate dehydrogenase release (LDH) and Nitric Oxide (NO) release supported the cytotoxic nature of the compounds. The results of all the biological studies carried out implied that the complex 3 bearing an ethyl substituent was observed to be the best. [ABSTRACT FROM AUTHOR]

The first X-ray structures of adducts formed between a RuII(N-heterocyclic carbene)(η6-p-cymene) compound and a protein are reported. Coordination to the protein induced the cleavage of the cymene ligand and EPR spectroscopy demonstrated the oxidation of the Ru centre. [ABSTRACT FROM AUTHOR]

We report the synthesis and characterization of four neutral organometallic tethered complexes, [Ru(η6-Ph(CH2)3-ethylenediamine-N-R)Cl], where R = methanesulfonyl (Ms, 1), toluenesulfonyl (Ts, 2), 4-trifluoromethylbenzenesulfonyl (Tf, 3), and 4-nitrobenzenesulfonyl (Nb, 4), including their X-ray crystal structures. These complexes exhibit moderate antiproliferative activity toward human ovarian, lung, hepatocellular, and breast cancer cell lines. Complex 2 in particular exhibits a low cross-resistance with cisplatin. The complexes show potent catalytic activity in the transfer hydrogenation of NAD+ to NADH with formate as hydride donor in aqueous solution (310 K, pH 7). Substituents on the chelated ligand decreased the turnover frequency in the order Nb > Tf > Ts > Ms. An enhancement of antiproliferative activity (up to 22%) was observed on coadministration with nontoxic concentrations of sodium formate (0.5-2 mM). Complex 2 binds to nucleobase guanine (9-EtG), but DNA appears not to be the target, as little binding to calf thymus DNA or bacterial plasmid DNA was observed. In addition, complex 2 reacts rapidly with glutathione (GSH), which might hamper transfer hydrogenation reactions in cells. Complex 2 induced a dose-dependent G1 cell cycle arrest after 24 h exposure in A2780 human ovarian cancer cells while promoting an increase in reactive oxygen species (ROS), which is likely to contribute to its antiproliferative activity. [ABSTRACT FROM AUTHOR]

Organoruthenium compounds have been widely investigated for their anticancer activity. Here we use one of the classic ligand classes found in organometallics, i.e., N-heterocyclic carbenes (NHC), and coordinate them to the Ru(η6-p-cymene) scaffold as N,C-bidentate ligands substituted with a pyridyl moiety. Introduction of different substituents gave compounds with a wide variety of properties. We investigated their stability in solution and in the presence of biomolecules, in vitro anticancer activity, and cellular uptake to rationalize their biological properties in dependence on the structure. A clear effect of their structure on the stability in water and DMSO was found for some derivatives, which was reflected in the reactivity to biomolecules that was determined with selected representatives of the compound classes. The antiproliferative activity of the compounds was widely dependent on the lipophilicity of the N,C-bidentate ligand, but as cellular accumulation studies revealed, lipophilicity does not provide the full picture and additional effects must be responsible for the anticancer activity. [ABSTRACT FROM AUTHOR]

Treatment of metalloligand [Ni(tsalphen)] (tsalphen =  N , N ′-bis(2-thiobenzylidene)-1,2-phenylenediaminato) with [( η 6 - p -cymene)RuCl( μ -Cl)] 2 or [CpRu(PPh 3 ) 2 Cl] afforded cationic “Ni( μ -S) 2 Ru” bimetallic complexes [( η 6 - p -cymene)Ru{Ni(tsalphen)}(MeCN)](OTf) 2 ( 1 ) and [CpRu{Ni(tsalphen)}(PPh 3 )] 2 (NiCl 4 )⋅4MeOH ( 2 ), respectively, which are characterized by single-crystal X-ray diffraction, and their catalytic activity for acetalation of benzaldehyde in the presence of H 2 was also investigated. [ABSTRACT FROM AUTHOR]

Ru(arene) compounds have many desirable features making them promising candidates for further development in anticancer drug research. While a lot of emphasis has been placed on the modification of the ancillary ligands, there are not many examples of arene ligands bearing functional groups. Herein, we report the preparation of [Ru(arene)(8-oxyquinolinato)Cl] complexes with the arene being a protected form of the amino acid l-phenylalanine and 8-oxyquinolinato ligand substituted with halogens. With this approach we aimed to alter the pharmacological properties of the complexes and address issues with the aqueous solubility of the analogous p-cymene complexes. The complexes were shown to be stable in DMSO and water and reacted readily with l-histidine and 9-ethylguanine as protein and DNA models, respectively. Assaying the antiproliferative activity in cancer cells gave IC50 values in the low μM range. While the lipophilicity of the p-cymene analogues correlated well with their in vitro cytotoxicity, the potency of the complexes with the l-phenylalanine-derived arene was independent of lipophilicity. [ABSTRACT FROM AUTHOR]

The ruthenium-arene complexes [(η6-p-cymene)RuCl2(κP-PPh2(4-C6H4CO2H))], 1, [(η6-p-cymene)RuCl(κ2P,O-PPh2(2-C6H4CO2))], 2, [(η6-p-cymene)RuCl2(κP-PPh2(2-C6H4OCO-EA))], 3, and [(η6-p-cymene)RuCl2(κP-PPh2(4-C6H4CO2CH2CH2OCO-EA))], 4 (EA-CO2H = ethacrynic acid), were synthesized in good to high yields and characterized by analytical techniques, IR, UV-Vis and multinuclear NMR spectroscopy, and single crystal X-ray diffraction in the cases of 1 and 2. The unstable compounds [(η6-arene)RuCl2(κP-PPh2(2-C6H4CO2CH2CH2OCO-EA))] (arene = p-cymene, 5a; arene = C6H6, 5b) were obtained and identified in solution by NMR. Electrochemical and spectro-electrochemical experiments were performed in order to assess the redox behaviour of 1–4 in CH2Cl2. The in vitro cytotoxicity of 1–4 was determined on the human pancreatic cancer cell line BxPC3 and the mouse embryo fibroblast Balb/3T3 Clone A31 cell line, the latter acting as a model for normal cells. Furthermore, the interaction of 1, 3 and 4 with two model proteins was investigated by high resolution ESI-MS. [ABSTRACT FROM AUTHOR]

Ru(II) and Os(II) complexes of 2-pyridinecarbothioamide ligands were introduced as orally administrable anticancer agents (S.M. Meier, M. Hanif, Z. Adhireksan, V. Pichler, M. Novak, E. Jirkovsky, M.A. Jakupec, V.B. Arion, C.A. Davey, B.K. Keppler, C.G. Hartinger, Chem. Sci. , 2013 , 4 , 1837–1846 ). In order to identify structure-activity relationships, a series of N -phenyl substituted pyridine-2-carbothiamides (PCAs) were obtained by systematically varying the substituents at the phenyl ring. The PCAs were then converted to their corresponding Ru II ( η 6 - p -cymene) complexes and characterized spectroscopically and by X-ray diffraction as well as in terms of stability in water and HCl. The cytotoxic activity of the PCA ligands and their respective organoruthenium compounds was evaluated in a panel of cell lines (HCT116, H460, SiHa and SW480). The lipophilic PCAs 1 – 4 showed cytotoxicity in the low micromolar range and 6 was the most potent compound of the series with an IC 50 value of 1.1 μM against HCT116 colon cancer cells. These observations were correlated with calculated octanol/water partition coefficient (clog P ) data and quantitative estimated druglikeness. A similar trend as for the PCAs was found in their Ru complexes, where the complexes with more lipophilic ligands proved to be more cytotoxic in all tested cell lines. In general, the PCAs and their organoruthenium derivatives demonstrated excellent drug-likeness and cytotoxicity with IC 50 values in the low micromolar range, making them interesting candidates for further development as orally active anticancer agents. [ABSTRACT FROM AUTHOR]

The potential use of organoruthenium complexes as anticancer drugs is well known. Herein, a family of activatable tethered ruthenium(II) arene complexes of general formula [Ru{η6:κ1-C6H5(C6H4)NH2}(XY)] n+ (closed tether ring) bearing different chelating XY ligands (XY=aliphatic diamine, phenylenediamine, oxalato, bis(phosphino)ethane) is reported. The activation of these complexes (closed- to open-tether conversion) occurs in methanol and DMSO at different rates and to different reaction extents at equilibrium. Most importantly, RuII-complex activation (cleavage of the Ru−Ntether bond) occurs in aqueous solution at high proton concentration (upon Ntether protonation). The activation dynamics can be modulated by rational variation of the XY chelating ligand. The electron-donating capability and steric hindrance of XY have a direct impact on the reactivity of the Ru−N bond, and XY= N, N′-dimethyl-, N, N′-diethyl-, and N, N, N′, N′-tetramethylethylenediamine afford complexes that are more prone to activation. Such activation in acidic media is fully reversible, and proton concentration also governs the deactivation rate, that is, tether-ring closure slows down with decreasing pH. Interaction of a closed-tether complex and its open-tether counterpart with 5′-guanosine monophosphate revealed selectivity of the active (open) complex towards interaction with nucleobases. This work presents ruthenium tether complexes as exceptional pH-dependent switches with potential applications in cancer research. [ABSTRACT FROM AUTHOR]

Our study demonstrates that four novel kinetically inert C, N-cyclometalated RuII complexes of the type [Ru(C^N)(N^N)2][PF6] containing a handle for functionalization on the C^N ligand are very potent cytotoxic agents against several different human cancer cell lines and are up to 400-fold more potent than clinically used cisplatin. In addition, the investigated ruthenium complexes are less cytotoxic in noncancerous cells, and exhibit higher selectivity for cancer cells than conventional platinum anticancer drugs. The high potency of the investigated ruthenium compounds can be attributed to several factors, including enhanced internalization and their capability to change mitochondrial transmembrane potential in cells. The new ruthenium complexes also interfere with protein synthesis with a markedly higher potency than conventional inhibitors of DNA translation. Notably, the latter mechanism has not been hitherto described for other cytotoxic Ru compounds and cisplatin. [ABSTRACT FROM AUTHOR]

Within this work we aimed to improve the pharmacodynamics and toxicity profile of organoruthenium and -rhodium complexes which had previously been found to be highly potent in vitro but showed unselective activity in vivo. Different organometallic complexes were attached to a degradable poly(organo)phosphazene macromolecule, prepared via controlled polymerization techniques. The conjugation to hydrophilic polymers was designed to increase the aqueous solubility of the typically poorly soluble metal-based half-sandwich compounds with the aim of a controlled, pH-triggered release of the active metallodrug. The synthesized conjugates and their characteristics have been thoroughly studied by means of 31P NMR and UV-Vis spectroscopy, ICP-MS analyses and SEC coupled to ICP-MS. In order to assess their potential as possible anticancer drug candidates, the complexes, as well as their respective macromolecular prodrug formulations were tested against three different cancer cell lines in cell culture. Subsequently, the anticancer activity and organ distribution of the poly(organo)phosphazene drug conjugates were explored in vivo in mice bearing CT-26 colon carcinoma. Our investigations revealed a beneficial influence of this macromolecular prodrug by a significant reduction of adverse effects compared to the free metallodrugs. [ABSTRACT FROM AUTHOR]

The synthesis of a range of new cyclometallated organoruthenium(II) complexes through the ortho-C−H activation of the aryl group in 2-aryl-substituted quinazolines with [RuX2( p-cymene)]2 is described. The beneficial effect of the carboxylate ligand on both the cyclometallation and the further arylation reaction step was demonstrated. Mechanistic studies reveal that bromide and iodide anions decelerate the arylation process by an in situ ligand exchange reaction. Additionally, a detailed NMR spectroscopy investigation was performed to explain some elementary steps in the arylation of 2-(aryl)quinazoline halidoruthenacycles. [ABSTRACT FROM AUTHOR]

Cyclopentadienyl ruthenium(ii) thiosemicarbazone complexes with the general formula [Ru(η5-C5H5)(Ac-tsc)PPh3]·Cl (1), [Ru(η5-C5H5)(Ac-mtsc)PPh3]·Cl (2), [Ru(η5-C5H5)(Ac-etsc)PPh3]·Cl (3) and [Ru(η5-C5H5)(Ac-ptsc)PPh3] (4) were synthesized and characterized by various spectroscopic techniques (1H NMR, 13C NMR, IR and UV-vis). The molecular structures of the representative complexes 2 and 4 were studied by single-crystal X-ray diffraction. The interactions of all the ligands and complexes with calf thymus DNA (CT-DNA) and bovine serum albumin (BSA) were studied using UV-vis and fluorescence emission spectroscopy. The results of binding studies revealed that the effective binding potentials of the complexes were higher than those of their parent ligands. All the new complexes 1–4 were investigated for their in vitro cytotoxic activity against MCF-7 human breast cancer cell line. All the complexes significantly inhibited cell proliferation in MCF-7 cells in a dose-dependent manner. Cytological observations via an inverted phase contrast microscope and a Hoechst 33342/PI dual-staining assay showed typical apoptotic morphology of cancer cells upon treatment with complexes 2 and 3. It can thus be suggested that the complexes 2 and 3 are modulated by apoptosis. The findings of the present study indicated that complexes 2 and 3 may become potent drugs for the treatment of cancer-related diseases only after further investigation. [ABSTRACT FROM AUTHOR]

Organometallic metal(arene) anticancer agents require ligand exchange for their anticancer activity and this is generally believed to confer low selectivity for potential cellular targets. However, using an integrated proteomics-based target-response profiling approach as a potent hypothesis-generating procedure, we found an unexpected target selectivity of a ruthenium(arene) pyridinecarbothioamide (plecstatin) for plectin, a scaffold protein and cytolinker, which was validated in a plectin knock-out model in vitro. Plectin targeting shows potential as a strategy to inhibit tumor invasiveness as shown in cultured tumor spheroids while oral administration of plecstatin-1 to mice reduces tumor growth more efficiently in the invasive B16 melanoma than in the CT26 colon tumor model. [ABSTRACT FROM AUTHOR]

The two complexes Ru ( II ) containing 2,6-bis(benzimidazol-2-yl)pyridine and 2-pyridine and 2-quinoline carboxylates were synthesized to fabricate organic photodiodes. The electrical properties of Au / Ru ( II ) complex ( I ) / n − Si / Al and Au / Ru ( II ) complex ( II ) / n − Si / Al diodes were investigated by current-voltage and capacitance-voltage measurements. The fabricated devices give a high rectification behavior with rectification ratio of 2.4 × 10 4 −2.1 × 10 3 at ± 4 V. The diodes exhibited a high photoconductivity based on trap levels within band gap. The series resistance and barrier height were calculated from ( C − V ) measurements and compared to other of ( I − V ) . The obtained results indicate that the prepared photodiodes can be used as photosensor for optoelectronic applications. [ABSTRACT FROM AUTHOR]

We report herein synthesis and characterization of four new organoruthenium(II) complexes of the type [RuH(CO)(PPh3)2(L1,2)]Cl (1,3) and [Ru(CO)(Cl)2(AsPh3)(L1,2)] (2,4) derived from the reaction of [RuHCl(CO)(EPh3)3] (E = P or As) with 2-(pyridine-2yl)benzoxazole (L1) and 2-(pyridine-2yl)benzthiazole (L2). Single-crystal X-ray diffraction data of2proved octahedral geometry of the complexes with a 1 : 1 ratio between the metal and the coordinated ligands. The binding affinities of1–4toward calf-thymus DNA (CT-DNA) and BSA were thoroughly studied by various spectroscopic techniques. Furthermore, the coordination compounds exhibit catecholase-like activities in the aerial oxidation of 3,5-di-tert-butylcatechol to the correspondingo-quinone and phosphatase-like activities in the hydrolysis of 4-nitrophenyl phosphate to 4-nitrophenolate ion. The kinetic parameters have been determined using Michaelis–Menten approach. The highestkcatvalues suggested that coordination compounds exhibit higher rates of catalytic efficacy. [ABSTRACT FROM PUBLISHER]

Helical twisting powers of a series of ruthenium complexes with screw-like Δ, Λ chirality were investigated inN-(4-Methoxybenzylidene)-4-butylaniline (MBBA). Λ-[Ru(acac)2(trop)] (acac = acetylacetonate, trop = tropolonate) shows a fairly low HTP of 18 µm−1, while we found that the HTP increased almost double by connecting with an achiral bulky unit [Ru(Cp)(dppe)] (Cp = cyclopentadienyl, dppe = 1,2-bis(diphenyl)phosphinoethane) that was found to behave as a molecular “picket fence” to force the orientation of surrounding MBBA molecules. [ABSTRACT FROM AUTHOR]

Four novel ruthenium organometallic complexes: [(η6-p-cymene)Ru(4,4,4-trifluoro-1-(4-bromophenyl)-1,3-butanedione)Cl] (1), [(η6-p-cymene)Ru(4,4,4-trifluoro-1-(4-bromophenyl)-1,3-but anedione)pta]PF6 (2), [(η6-p-cymene)Ru(4,4,4-trifluoro-1-(4-iodophenyl)-1,3-butanedione)Cl] (3) and [(η6-p-cymene)Ru(4,4,4-trifluoro-1-(4-iodophenyl)-1,3-butanedione)pta]PF6 (4) were synthesized and characterized by elemental analysis, infrared (IR), UV-Vis, NMR and mass spectroscopy and single-crystal X-ray diffraction. The crystal structures and spectroscopic data were compared to the previously published complexes [(η6-p-cymene)Ru(4,4,4-trifluoro-1-(4-chloro-phenyl)-1,3-butanedione)Cl] (5) and [(η6-p-cymene)Ru(4,4,4-trifluoro-1-(4-chlorophenyl)-1, 3-butanedione)pta]PF6 (6). The pairs of complexes 1 and 3 as well as 2 and 4 are isostructural, with the former crystallizing in triclinic P-1 and the latter in monoclinic P21/c. The ruthenium(II) ion is found in a pseudo-octahedral "piano-stool" geometry in all compounds. Bond lengths and angles are consistent with other complexes of this type. Complexes 2 and 4 exhibit some moderate dynamic disorder. The lack of hydrogen bonding and major π-π interactions means that most of intramolecular interactions are fairly weak and involve halogen atoms present. This was further confirmed by ¹H-NMR spectra, where a significant difference is observed only on the ligand near the halogen atom, following an expected trend. The combined data show that the difference in any activity depends substantially on the type of the ligand0s substituted halogen atom. [ABSTRACT FROM AUTHOR]

One pot synthesis of three structurally different ruthenium(II) carbonyl complexes [Ru(N,S-H-Nap-mtsc)(CO)Cl(PPh 3 ) 2 ]( 1a) , [Ru(N,N,S-H-Nap-mtsc)(CO)Cl(PPh 3 ) 2 ]( 1b) and [Ru(Nap-mtsc)(CO)(PPh 3 ) 2 ] ( 1c ) were prepared from a reaction of 2-hydroxy-1-naphthaldehyde-4( N )-methylthiosemicarbazone and [RuHCl(CO)(PPh 3 ) 3 ] in benzene. However, the same reaction in ethanol, methanol and DMF afforded only 1a and 1c . The new complexes were characterized by various spectro analytical techniques. The structure of the complexes 1a and 1c were solved by X-ray crystallography. In 1a the ligand behaved as bidentate monobasic by forming an unusual four member chelate ring. However, in 1c the ligand behaved as tridentate bibasic (ONS) donor by forming five and six member chelate rings. Attempts to crystallize 1b were unsuccessful due to the structural conversion of 1b to 1c . DFT studies were carried out to know more on the structural aspects of these new complexes. From the results, it is inferred that ONS chelate ( 1c ) has comparatively lesser energy than NS five ( 1b ) and four ( 1a ) member chelates. The structural conversion of 1b to 1c in polar solvents at room temperature prevents 1b to introduce for biological investigation. From the DNA binding studies, it is found that the complexes 1a and 1c bind through intercalative mode. In addition, they had a strong binding affinity with bovine serum albumin (BSA) through static quenching. The complexes 1a and 1c were subjected to in vitro cytotoxicity studies against human lung cancer cells (A549) and liver cancer cells (HepG2). The IC 50 values of the complexes 1a and 1c were found to be lower than cisplatin in A549 cell line. However, in HepG2 cell line; IC50 values were found in the following order 1c < cisplatin < 1a . Among the two metallates, 1c found to possess higher cytotoxicity and this may be due to the increase in electron delocalization within five and six member rings, which facilitates the reduction of electron density on ruthenium ion and subsequent increase in the cell permeability. [ABSTRACT FROM AUTHOR]

Herein, we have introduced a novel, green and effective methodology for the synthesis of Ru(ii)–arene 2-pyridinylbenzothiazole, Ru(ii)–arene 2-pyridinylbenzoxazole & Ru(ii)–arene 2-pyridinylbenzimidazole complexes in a one-pot sequence. A convenient and clean “on water” synthesis of organoruthenium is reported. Amberlite IR-120(H) has been employed as a reusable catalyst in this reaction. The operational simplicity, excellent yield, ease of product isolation and high chemoselectivity are the main advantages of this method; moreover, this process is economical, safe and environmentally benign. This method offers the opportunity of synthesizing a variety of newer organoruthenium scaffolds for anticancer screening. Most of the compounds presented here have displayed significant cytotoxicity & selectivity against MCF7, Hela and A2780 cell lines compared to cisplatin. Since, [(η6-p-cymene)Ru-2-(6-bromopyridin-2-yl)-benzo[d]thiazole] (4g) was identified as the most potent fluorescent scaffold in terms of cytotoxicity & selectivity in the cancer cell lines, it might be used in cancer theranostics. [ABSTRACT FROM AUTHOR]

Reaction of [RuC6H6Cl2]2 with TeO2 and Na2WO4·2H2O in aqueous solution (pH 4.7) yielded a novel organo-ruthenium supported tungstotellurate polyanion, [Te2W20O70(RuC6H6)2]8− (Ru-1), which is composed of two [RuC6H6]2+ units linked to a [Te2W20O70]12− fragment through Ru–O(W) bonds resulting in an assembly with idealized C2h symmetry. Furthermore, the polyanion Ru-1 was anchored on 3-aminopropyltriethoxysilane (apts)-modified SBA-15 to prepare new catalysts (SBA-15–apts–Ru-1) containing different amounts of Ru-1, which were characterized using powder X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), N2-adsorption measurement and Fourier transform infrared reflectance (FT-IR) spectroscopy. Finally, the catalytic activity of SBA-15–apts–Ru-1 was evaluated for the aerobic oxidation of n-tetradecane using air as the oxidant in the absence of any additives or solvents. In addition, the optimum catalytic reaction conditions were also determined. [ABSTRACT FROM AUTHOR]

Three new ruthenium(II)–arene halido complexes of general formula [(η 6 - p -cymene)RuX(L)] ( C1 C3 ) were synthesised by reaction of [(η 6 - p -cymene)RuX 2 ] 2 (X − = Cl − , Br − , I − ) with 1 H -benzimidazole-2-carboxylic acid (HL) in ethanol. The complexes were characterised by elemental analysis, mass spectrometry, IR, 1 H and 13 C NMR spectroscopy. The 1 H -benzimidazole-2-carboxylate was found to act as a bidentate N,O–chelating ligand. Single-crystal X-ray diffraction analysis confirmed the “piano-stool” geometry of C3 . The cytotoxic activity of the ligand precursor and ruthenium complexes was tested in human cancer cell lines: cervical carcinoma (HeLa), breast carcinoma (MDA-MB-231), myelogenous leukemia (K562) as well as in one normal human fetal lung fibroblast cell line (MRC-5), by MTT assay. The results show that ruthenium(II)-arene complexes possess enhanced cytotoxicity when compared to that of HL. The latter was devoid of activity in the range of concentrations up to 300 μM. Complex C3 , carrying an iodido leaving ligand, exhibited moderate, but selective cytotoxicity toward HeLa, MDA-MB-231 and K562 cell lines, with IC 50 values: 73.7, 60.9 and 53.9 μM, respectively, being less toxic against MRC-5 cells (IC 50 = 175.9 μM). Complexes C1 and C2 showed moderate to low cytotoxicity in HeLa and K562 cells. [ABSTRACT FROM AUTHOR]

This article outlines the synthesis of an electrophilic organoruthenium carboxylic acid of the structure [(η 5 -Cp*)Ru(η 6 -C 6 H 5 CO 2 H)] + and explores the behavior of this molecule under a variety of nucleophilic substitution conditions using a range of oxygen and nitrogen based nucleophiles including alcohols, primary and secondary amines and aromatic sulfonamides. The resulting organoruthenium ester [(η 5 -Cp*)Ru(η 6 -C 6 H 5 COOR)] + and amide [(η 5 -Cp*)Ru(η 6 -C 6 H 5 CONHR)] + or [(η 5 -Cp*)Ru(η 6 -C 6 H 5 CONR)] + complexes are additionally reported. All prepared complexes have been fully characterized using Fourier-transform IR and NMR spectroscopy and electrospray mass spectrometry with single-crystal X-ray structural determinations reported for three complexes: 3[(η 5 -Cp*)Ru(η 6 -C 6 H 5 CO 2 H)]B(C 6 H 5 ) 4 .[(η 5 -Cp*)Ru(η 6 -C 6 H 5 CO 2 )].H 2 O, [(η 5 -Cp*)Ru(η 6 -C 6 H 5 CONHCH 2 Ph)]PF 6 and [(η 5 -Cp*)Ru(η 6 -C 6 H 5 CONHSO 2 C 6 H 4 COMe)]PF 6 . Complexes were also evaluated for in vitro cytotoxic activity against the MCF7 (hormone-dependant breast cancer), MDA-MD-231 (hormone-independent breast cancer), MM96L (human melanoma) tumourigenic cell lines and the normal NFF (neonatal foreskin fibroblasts) human cell line. [ABSTRACT FROM AUTHOR]

Four ruthenium complexes of clinically used zinc ionophore pyrithione and its oxygen analog 2-hydroxypyridine N-oxide were prepared and evaluated as inhibitors of enzymes of the aldo–keto reductase subfamily 1C (AKR1C). A kinetic study assisted with docking simulations showed a mixed type of inhibition consisting of a fast reversible and a slow irreversible step in the case of both organometallic compounds 1A and 1B. Both compounds also showed a remarkable selectivity towards AKR1C1 and AKR1C3 which are targets for breast cancer drug design. The organoruthenium complex of ligand pyrithione as well as pyrithione itself also displayed toxicity on the hormone-dependent MCF-7 breast cancer cell line with EC50 values in the low micromolar range. [ABSTRACT FROM AUTHOR]

Herein we report investigation of the interactions between anticancer organoruthenium complexes, [(η 6 -arene)Ru(en)(Cl)]PF 6 (en = ethylenediamine, arene = p -cymene ( 1 ) or biphenyl ( 2 )), and the human copper chaperone protein Cox17 by mass spectrometry with cisplatin as a reference. The electrospray ionization mass spectrometry (ESI-MS) results indicate much weaker binding of the ruthenium complexes than that of cisplatin to apo-Cox17 2s-s , the functional state of Cox17. Up to tetra-platinated Cox17 adducts were identified while only mono-ruthenated and a little amount of di-ruthenated Cox17 adducts were detected even for the reactions with 10-fold excess of the Ru complexes. However, ESI-MS analysis coupled with liquid chromatography of tryptic digests of metalated proteins identified only three platination sites as Met4, Cys27 and His47 residues, possibly due to the lower abundance or facile dissociation of Pt bindings at other sites. Complexes 1 and 2 were found to bind to the same three residues with Met4 as the major site. Inductively coupled plasma mass spectrometry results revealed that ~ 7 mol Pt binding to 1 mol apo-Cox17 2s-s molecules, compared to only 0.17 ( 1 ) and 0.10 ( 2 ) mol Ru to 1 mol apo-Cox17 2s-s . This is in line with the circular dichroism results that much larger unfolding extent of α-helix of apo-Cox17 2s-s was observed upon cisplatin binding than that upon organoruthenium bindings. These results collectively indicate that Cox17 might not participate in the action of these anticancer organoruthenium complexes, and further verify the distinct anticancer mechanism of the organoruthenium(II) complexes from cisplatin. [ABSTRACT FROM AUTHOR]

Two previously isolated cytotoxic complexes [(η 6 - p -cymene)Ru(κ 2 -CF 3 C O CH C OC 5 H 3 O)L] n + (L = Cl ( 1 ); n = 0, pta ( 2 ) (pta = 1,3,5-triaza-7-phosphaadamantane); n = 1) were investigated for their selectivity and ability to interact with DNA G-quadruplex adopted by d[G 3 ATG 3 ACACAG 4 ACG 3 ] ( 3 ) whose topology exhibits diagonal, edge-type and double-chain reversal loops. Structural changes were followed using high-resolution NMR techniques in the presence of 1 and 2 . Results showed weak interaction between the organoruthenium complexes and G-quadruplex. Moreover, no significant changes in thermal stability were confirmed by a UV-melting assay for both 1 and 2 . These findings emphasize that anticancer activity of Ru(II) complexes may not be correlated with binding to nucleic acid like G-quadruplex. [ABSTRACT FROM AUTHOR]

The rapidly growing area of catalytic ruthenium chemistry has provided new complexes with potential as organometallic anticancer agents with novel mechanisms of action. Here we report the anticancer activity of four neutral organometallic RuII arene N-tosyl-1,2-diphenylethane-1,2-diamine (TsDPEN) tethered transfer hydrogenation catalysts. The enantiomers (R,R)-[Ru(η6-C6H5(CH2)3-TsDPEN-N-Me)Cl] (8) and (S,S)-[Ru(η6-C6H5(CH2)3-TsDPEN-N-Me)Cl] (8a) exhibited higher potency than cisplatin against A2780 human ovarian cancer cells. When the N-methyl was replaced by N–H, i.e. to give (R,R)-[Ru(η6-Ph(CH2)3-TsDPEN-NH)Cl] (7) and (S,S)-[Ru(η6-Ph(CH2)3-TsDPEN-NH)Cl] (7a), respectively, anticancer activity decreased ＞5-fold. Their antiproliferative activity appears to be linked to their ability to accumulate in cells, and their mechanism of action might involve inhibition of tubulin polymerisation. This appears to be the first report of the potent anticancer activity of tethered RuII arene complexes, and the structure–activity relationship suggests that the N-methyl substituents are important for potency. In the National Cancer Institute 60-cancer-cell-line screen, complexes 8 and 8a exhibited higher activity than cisplatin towards a broad range of cancer cell lines. Intriguingly, in contrast to their potent anticancer properties, complexes 8/8a are poor catalysts for asymmetric transfer hydrogenation, whereas complexes 7/7a are effective asymmetric hydrogenation catalysts. [ABSTRACT FROM AUTHOR]

Construction of a site-isolated heterogeneous catalyst to realize the compatibility of bimetallic complexes for a feasible tandem reaction is a significant challenge in heterogeneous asymmetric catalysis. Herein, taking advantage of yolk–shell-structured mesoporous silica, we assemble an active site-isolated bifunctional catalyst through assembly of organopalladium-functionality into silicate channels as an outer shell and chiral organoruthenium-functionality onto silicate yolk as an inner core, realizing the one-pot enantioselective tandem reaction from Pd-catalyzed Sonogashira coupling to Ru-catalyzed asymmetric transfer hydrogenation. As presented in this study, this tandem Sonogashira coupling–asymmetric transfer hydrogenation of haloacetophenones and arylacetylenes affords various chiral conjugated alkynols with high yields and up to 99% enantioselectivity. Moreover, a catalyst can also be recovered easily and recycled repeatedly, making it an interesting feature in a practical organic transformation. [ABSTRACT FROM AUTHOR]

The reaction of a platinum acetylide derived from a 1,2-dialkynylarene with a phosphanegold(I) species delivered a σ-platinum-π-gold coordination to the same triple bond of the organic substrate. Cyclopentadienyl-di(phosphanyl)ruthenium(II) acetylides of the same substrate type gave vinylgold(I)-vinylideneruthenium(II) complexes in similar reactions. A switch to the corresponding cyclopentadienyl-di(carbonyl)ruthenium(II) species with a phenyl group on the second alkyne provided vinylruthenium(II) complexes in which the ruthenium was still bound to the same carbon as in the starting material, with a tert-butyl group on the second alkyne vinylruthenium(II) complexes in which the ruthenium has migrated to another carbon, were obtained. This reactivity mimics the initial steps suggested for dual gold catalysis with these substrates and thus for the first time experimentally confirms the organometallic reactivity patterns proposed for the single steps. [ABSTRACT FROM AUTHOR]

Four organometallic complexes [(η6-C6H6)RuCl(pmpzdpm)], 1; [(η6-C6H6)RuCl(pypzdpm)], 2; [(η6-C10H14)RuCl(pmpzdpm)], 3 and [(η6-C10H14)RuCl(pypzdpm)], 4 containing 5-(2-pyrimidyl-piperazine)phenyldipyrromethene (pmpzdpm) and 5-(2-pyridylpiperazine)phenyldipyrromethene (pypzdpm) have been designed and synthesized. The complexes 1–4 have been fully characterized by elemental analyses and spectroscopic studies (ESI-MS, IR, 1H, 13C NMR, UV–vis). Their electrostatic/intercalative interaction with CT DNA has been investigated by UV–vis and competitive ethidium bromide displacement studies while their protein binding affinity toward bovine serum albumin (BSA) was realized by UV–vis, fluorescence, synchronous and three dimensional (3D) fluorescence studies. The interaction with DNA and protein has further been validated by in silico studies. Cellular uptake, in vitro cytotoxicity and flow cytometric analyses have been performed to determine the mode of cell death against the kidney cancer cell line ACHN. Cell cycle analysis suggested that the complexes cause cell cycle arrest in the subG1 phase and overall results indicated that the in vitro antitumor activity of 1–4 lies in the order of 3 ＞ 4 ＞ 1 ＞ 2 (IC50, 7.0 1; 8.0 2; 2.0 3; 4.0 μM, 4). [ABSTRACT FROM AUTHOR]

8-Hydroxyquinoline and its derivatives have a broad variety of pharmacological properties, which make them an ideal bioactive building block in the development of metal-based anticancer drugs. In this account we aimed to rationalize the antiproliferative efficacy of organoruthenium compounds featuring 8-hydroxyquinoline-derived ligands and to elucidate structural determinants by using biological assays and bioanalytical methods. By systematically varying the halide substitution pattern at the 5- and 7-positions of the 8-hydroxyquinoline ligand, as well as the halido leaving group, a series of 5,7-dihalido-8-hydroxyquinoline RuII(η6-p-cymene) complexes were obtained. Studies on their cytotoxic activity revealed the minor impact of the substitution pattern (with the exception of complexes of 8-hydroxyquinoline) on their activity. Notably, the cellular accumulation showed no correlation with the cytotoxic activity, while the nature of the halido leaving group only had a significant influence in the case of the 8-hydroxyquinoline organoruthenium compounds. However, the compounds were shown to be very stable under a wide variety of pH conditions, making them possible candidates for further development as orally active anticancer agents. [ABSTRACT FROM AUTHOR]

We have recently demonstrated that complexation with (η6-arene)RuII fragments confers 4-anilinoquinazoline pharmacophores a higher potential for inducing cellular apoptosis while preserving the highly inhibitory activity of 4-anilinoquinazolines against EGFR and the reactivity of the ruthenium centre to 9-ethylguanine (Chem. Commun., 2013, 49, 10224–10226). Reported herein are the synthesis, characterisation and evaluation of the biological activity of a new series of ruthenium(ii) complexes of the type [(η6-arene)Ru(N,N-L)Cl]PF6 (arene = p-cymene, benzene, 2-phenylethanol or indane, L = 4-anilinoquinazolines). These organometallic ruthenium complexes undergo fast hydrolysis in aqueous solution. Intriguingly, the ligation of (arene)RuII fragments with 4-anilinoquinazolines not only makes the target complexes excellent EGFR inhibitors, but also confers the complexes high affinity to bind to DNA minor grooves while maintaining their reactivity towards DNA bases, characterising them with dual-targeting properties. Molecular modelling studies reveal that the hydrolysis of these complexes is a favourable process which increases the affinity of the target complexes to bind to EGFR and DNA. In vitro biological activity assays show that most of this group of ruthenium complexes are selectively active inhibiting the EGF-stimulated growth of the HeLa cervical cancer cell line, and the most active complex [(η6-arene)Ru(N,N-L13)Cl]PF6 (4, IC50 = 1.36 μM, L13 = 4-(3′-chloro-4′-fluoroanilino)-6-(2-(2-aminoethyl)aminoethoxy)-7-methoxyquinazoline) is 29-fold more active than its analogue, [(η6-arene)Ru(N,N-ethylenediamine)Cl]PF6, and 21-fold more active than gefitinib, a well-known EGFR inhibitor in use clinically. These results highlight the strong promise to develop highly active ruthenium anticancer complexes by ligation of cytotoxic ruthenium pharmacophores with bioactive organic molecules. [ABSTRACT FROM AUTHOR]