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A series of neutral ruthenium(ii)-arene complexes, [(arene)Ru(Q R )Cl] (arene = p-cymene or hexamethylbenzene), containing 4-acyl-5-pyrazolonate (Q R ) ligands with aromatic substituents in the acyl moiety (a phenyl in Q Ph and a 1-naphthyl in Q naph ) and related ionic complexes [(arene)Ru(Q R )(PTA)][PF 6 ] (PTA = 1,3,5-triaza-7-phosphaadamantane) have been synthesized and characterized by IR, 1 H, 13 C and 31 P NMR spectroscopy, elemental analysis and ESI mass spectrometry. The structures of five of these compounds were also determined by X-ray crystallography. DFT studies have been performed on all complexes and, in the case of two cationic [(arene)Ru(Q naph )(PTA)][PF 6 ], the existence of two conformers with a different relative orientation of the naphthyl group in the Q naph ligand has been assessed, showing that they possess similar energies, in agreement with the experimentally observed NMR spectra in solution. The cytotoxicity of the 4-acyl-5-pyrazolonate proligands (HQ R ) and complexes was evaluated in vitro against human ovarian carcinoma cells (A2780 and A2780cisR) and non-tumorous human embryonic kidney (HEK293) cells. In general, each complex is about equally cytotoxic to all three cell lines and the PTA derivatives with the naphthyl-modified Q R ligands are the most active of the series.

Dinuclear metal complexes have emerged as a promising class of anticancer compounds with the ability to cross-link biomolecular targets. Here, we describe two novel series of phosphine-linked dinuclear ruthenium(II) p-cymene and gold(I) complexes, in which the length of the connecting poly(ethylene glycol) chain has been systematically modified. The impact of the multinuclearity, lipophilicity, and linker length on the antiproliferative activity of the compounds on tumorigenic (A2780 and A2780cisR) and nontumorigenic (HEK-293) cell lines was assessed. The dinuclear ruthenium(II) complexes were considerably more cytotoxic than their mononuclear counterparts, and a correlation between the lipophilicity of the linker and the cytotoxicity was observed, whereas the cytotoxicity of the gold(I) series is independent of these factors.

A series of neutral ruthenium(II) arene complexes [(arene)Ru(Q R )Cl] (arene = p-cymene (cym) or hexamethylbenzene (hmb)) containing 4-acyl-5-pyrazolonate Q R ligands with different electronic and steric substituents (R = 4-cyclohexyl, 4-stearoyl, or 4-adamantyl) and related ionic complexes [(arene)Ru(Q R )(PTA)][PF 6 ] (PTA = 1,3,5-triaza-7-phosphaadamantane) were synthesized and characterized by spectroscopy (IR, UV-vis, ESI-MS, and 1 H and 13 C NMR), elemental analysis, X-ray crystallography, and density functional theory studies. The cytotoxicity of the proligands and metal complexes was evaluated in vitro against human ovarian carcinoma cells (A2780 and A2780cisR), as well as against nontumorous human embryonic kidney (HEK293) cells. In general the cationic PTA-containing complexes are more cytotoxic than their neutral precursors with a chloride ligand in place of the PTA. Moreover, the complexes do not show cross-resistance and are essentially equally cytotoxic to both the A2780 and A2780cisR cell lines, although they only show limited selectivity toward the cancer cell lines.

Following the identification of [Ru(η(6)-p-cymene)Cl2(1H,1H,2H,2H-perfluorodecyl-3-(pyridin-3-yl)propanoate)], a ruthenium(II)-arene complex with a perfluoroalkyl-modified ligand that displays remarkable in vitro cancer cell selectivity, a series of structurally related compounds were designed. In the new derivatives, the p-cymene ring and/or the chloride ligands are substituted by other ligands to modulate the steric bulk or aquation kinetics. The new compounds were evaluated in both in vitro (cytotoxicity and migration assays) and in vivo (chicken chorioallantoic membrane) models and were found to exhibit potent antivascular effects.

Novel ruthenium half-sandwich complexes containing (N,O)-bound pyrazolone-based β-ketoamine ligands have been prepared, and the solid-state structures of one ligand and five complexes have been determined by single-crystal X-ray diffraction. Some of the complexes display moderate cytotoxicity toward the human ovarian cancer cell lines A2780 and A2780cisR, the latter line having acquired resistance to cisplatin.

The reactions of arene-metal complexes (arene=p-cymene, benzene or pentamethylcyclopentadienyl, metal=Ru, Rh or Os), including 1,3,5-triaza-7-phosphatricyclo-[3.3.1.1]decanephosphine (pta) and chloro co-ligands, with 9-methylguanine, adenine, and a series of nucleosides were studied in water to ascertain the binding modes. The products were characterized by NMR spectroscopy and electrospray ionization mass spectrometry (ESI-MS). Tandem mass spectrometry was found to provide excellent information on preferential binding sites. In general, the N7 position on guanine (the most basic site) was found to be the preferred donor atom for coordination to the metal complexes. The X-ray structures of the precursor complexes, [(eta5-C10H15)RhCl(pta-Me)2]Cl2, [(eta6-C10H14)OsCl(pta)2]Cl, and [(eta6-C6H6)OsCl2(CH3CN)], are also reported.

Organometallic ruthenium(II) complexes of the general formula [Ru(eta6-p-cymene)Cl2(L)] and [Ru(eta6-p-cymene)Cl(L)2][BPh4] with modified phenoxazine- and anthracene-based multidrug resistance (MDR) modulator ligands (L) have been synthesized, spectroscopically characterized, and evaluated in vitro for their cytotoxic and MDR reverting properties in comparison with the free ligands. For an anthracene-based ligand, coordination to a ruthenium(II) arene fragment led to significant improvement of cytotoxicity as well as Pgp inhibition activity. A similar, but weaker effect was also observed when using a benzimidazole-phenoxazine derivative as Pgp inhibitor. The most active compound in terms of both Pgp inhibition and cytotoxicity is [Ru(eta6-p-cymene)Cl2(L)], where L is an anthracene-based ligand. Studies show that it induces cell death via inhibition of DNA synthesis. Moreover, because the complex is fluorescent, its uptake in cells was studied, and relative to the free anthracene-based ligand, uptake of the complex is accelerated and accumulation of the complex in the cell nucleus is observed.

With a view to develop drugs that could resist hydrolysis in aqueous media, organometallic arene-capped ruthenium(II) 1,3,5-triaza-7-phosphatricyclo[3.3.1.1]decane (RAPTA) complexes bearing chelating carboxylate ligands have been prepared and studied. The new complexes, Ru(eta6-cymene)(PTA)(C2O4) (1) and Ru(eta6-cymene)(PTA)(C6H6O4) (2), were found to be highly soluble and kinetically more stable than their RAPTA precursor that contains two chloride ligands in place of the carboxylate ligands. They were also able to resist hydrolysis in water and exhibited significantly lower pKa values. Importantly, they showed a similar order of activity in inhibiting cancer cell-growth proliferation (as determined by in vitro assays) and exhibited oligonucleotide binding characteristics (as evidenced by matrix-assisted laser desorption ionization mass spectrometry) similar to those of the RAPTA precursor, hence realizing a strategy for developing a new generation of stable and highly water-soluble RAPTA adducts.

Ten complexes of general formula [Ru(eta6-arene)Cl2(L)], [Ru(eta6-arene)Cl(L)2][X], and [Ru(eta6-arene)(L)3][X]2 (eta6-arene = benzene, p-cymene; L = imidazole, benzimidazole, N-methylimidazole, N-butylimidazole, N-vinylimidazole, N-benzoylimidazole; X = Cl, BF4, BPh4) have been prepared and characterized by spectroscopy. The structures of five representative compounds have been established in the solid state by single-crystal X-ray diffraction. All the new compounds were assessed by the same in vitro screening assays applied to [imidazole-H][trans-RuCl4(DMSO)(imidazole)] (NAMI-A) and [Ru(eta6-arene)Cl2(1,3,5-triaza-7-phosphaadamantane)] (RAPTA) compounds. It was found that the new compounds show essentially the same order of cytotoxicity as the RAPTA compounds toward cancer cells. Several of the compounds were selective toward cancer cells in that they were less (or not) cytotoxic toward nontumorigenic cells that are used to model healthy human cells. Thus, two of the compounds, [Ru(eta6-p-cymene)Cl(vinylimid)2][Cl] (vinylimid = N-vinylimidazole) and [Ru(eta6-benzene)(mimid)3][BF4]2 (mimid = N-methylimidazole), have been selected for a more detailed in vivo evaluation.

Vinyl triazenes were obtained by enantioselective [2+2] cycloaddition reactions of bicyclic alkenes with 1-alkynyl triazenes in the presence of a RuII catalyst with a chiral cyclopentadienyl ligand. These triazenes serve as unique vinyl cation surrogates. Under acidic conditions, the triazene functionality can be replaced with a variety of groups, including halides, alkoxides, sulfoxides, amides, arenes, and heteroarenes, thus providing efficient access to a pool of chiral polycyclic compounds. [ABSTRACT FROM AUTHOR]

Dicationic ruthenium(II)-p-cymene complexes containing curcumin ligands (curcH = curcumin, bdcurcH = bisdemethoxycurcumin) and ionic N-methyl-1,3,5-triaza-7-phosphaadamantane [PTA-Me]X (X = BF4 or I) have been synthesized and fully characterized for the first time. The solid-state structure of [Ru(p-cym)(curc)(PTA-Me)][SO3CF3][BF4] has also been determined by single-crystal X-ray diffraction. Modest antiproliferative activities of the complexes were observed against cisplatin-sensitive and cisplatin-resistant human ovarian carcinoma cells (A2780 and A2780cisR, respectively) and nontumorigenic human embryonic kidney (HEK293) cells. [ABSTRACT FROM AUTHOR]

Imidazolin-2-imine and imidazolidin-2-imine ligands are versatile N donors in transition metal chemistry. Here, we describe the synthesis and characterization of (arene)Ru complexes with these ligands. Simple adducts of the type [( p-cymene)Ru(L)Cl2] (L = 1,3-diarylimidazolin-2-imine or 1,3-dimesitylimidalzolidin-2-imine) can be converted into complexes in which the imines act as π ligands with tethered imine groups. Furthermore, the high basicity of the N donor group can promote self-activation of the (arene)Ru complexes. [ABSTRACT FROM AUTHOR]

The dimeric ruthenium complex [Cp∧RuCl2]2 is easily accessible in a one-pot reaction from RuCl3(solv) n and tert-butylacetylene. It features sterically very demanding 'Cp-roof' ligands (Cp∧ = η5-1-methoxy-2,4- tert-butyl-3-neopentylcyclopentadienyl), which impart a unique reactivity. Herein we describe the synthesis and the characterization of novel Cp∧Ru complexes bearing a bridging carbene ligand, a linear imido ligand, or an orthometalated phosphine ligand. Furthermore, the microwave-assisted syntheses of the bimetallic complexes [Cp∧Ru(μ-Cl)3Ru( p-cymene)] and [Cp∧Ru(μ-Cl)3RhCp*] are described. [ABSTRACT FROM AUTHOR]

The dinuclear complexes [( p-cymene)RuCl2]2 and [(cyclopentadienyl)MCl2]2 (M = Ru, Rh, Ir) are important starting materials in organometallic chemistry. The standard synthesis of these complexes involves heating of an alcoholic solution of RuIII, RhIII, or IrIII salts with precursors of the π-ligands for several hours under reflux. Microwave heating allows these complexes to be obtained within a few minutes without compromising the yields. Furthermore, the microwave-assisted syntheses require less solvent and, in some cases, lower amounts of ligand precursors. [ABSTRACT FROM AUTHOR]

Ruthenium und Co: Ruthenium(II) ‐ Komplexe sind nach wie vor die „heißesten Kandidaten“ für Farbstoffsolarzellen, doch derzeit bekannte Ru ‐ Sensibilisatoren sind nicht mit CoII/III ‐ Elektrolyten kompatibel. Der Effekt einer Oberflächenisolierung auf die Leistungsfähigkeit einer Zelle wurde durch den Vergleich zweier cyclometallierter RuII ‐ Komplexe studiert. Der Ansatz zeigt ein allgemeines Prinzip für beispiellose Effizienzen bei der Kombination von RuII ‐ Sensibilisatoren mit einem Cobalt ‐ Elektrolyt. [ABSTRACT FROM AUTHOR]

The reaction of half-sandwich complexes of ruthenium, rhodium, and iridium with amino-substituted 3-hydroxy-2-pyridone ligands in aqueous solution gives monomeric O,O'-chelate complexes. Upon addition of base, the complexes assemble to form trimeric metallamacrocycles, as evidenced by NMR spectroscopy and single-crystal X-ray analyses. The macrocycles are able to act as highly selective receptors for lithium ions. The binding constants depend on the nature of the half-sandwich complex, the ligand, and the pH. With a commercially available (cymene)Ru complex, a receptor with a Li+ binding constant of Ka = 5.8 (±1.0) × 104 M-1 and a Li+--N+ selectivity of 10 000:1 can be obtained. The fact that the assembly process of the receptor is pH-dependent can be used to detect the presence of lithium ions by a pH measurement. Furthermore, it is possible to transduce the binding of Li+ into a change of color by means of a chemical reaction with FeCl3. This allows the detection of Li+ in the pharmacologically relevant concentration range of 0.5-1.5 mM by the "naked eye". [ABSTRACT FROM AUTHOR]

The reaction of [(arene)RuCl2]2 (arene = cymene, 1,3,5-C6H3Me3) and [Cp*RhCl2]2 half-sandwich complexes with tridentate heterocyclic ligands in the presence of base has been investigated. In all cases, the chloro-ligands were substituted to give metallacyclic products with ring sizes between 4 and 18 atoms. The cyclization occurs in a highly diastereoselective fashion with chiral recognition between the different metal fragments. The complexes were comprehensively characterized by elemental analysis, NMR spectroscopy, and single crystal X-ray crystallography. For 2-hydroxy-nicotinic acid and 2-amino-nicotinic acid, dinuclear structures were obtained (1517) whereas for 2,3-dihydroxyquinoline, 2,3-dihydroxyquinoxaline, and 6-methyl-2,3-phenazinediol, trimeric assemblies were found (19-22), and for 4-imidazolecarboxylic acid, a tetrameric assembly (18) was found. [ABSTRACT FROM AUTHOR]

Abstract: Metal complexes bearing phosphine ligands are attracting increasing attention for their applications in medicinal chemistry. In particular, organometallic ruthenium-phosphine complexes have been found to exhibit promising antitumour activity. The synthesis, anticancer activity and reactivity of a novel bis-phosphine complex, [Ru(η 6-cymene)(PPh2(o-C6H4O)-κ 2-P,O)(pta)]Cl (pta=1,3,5-triaza-7-phosphatricyclo[3.3.1.1.]decane), is presented. The complex appears to exhibit its anticancer effect via a different mechanism to other ruthenium-arene pta complexes with labile co-ligands. [Copyright &y& Elsevier]

Abstract: Organometallic half-sandwich complexes based on ruthenium with aminomethyl-substituted 3-hydroxy-2-pyridone ligands exist in aqueous solution as monomeric O,O′-chelate complexes or trimeric metallamacrocycles depending upon the pH. We hypothesized that administration of the compounds as stable trimers, which subsequently convert to active monomers at the reduced pH of the cancer environment, could facilitate their delivery to cancer cells without undergoing deactivation. Thus, the compounds were evaluated against cancer and fibroblast cell lines in vitro. A series of rhodium complexes, which exist mainly as monomers at neutral pH, were also studied for comparative purposes. [Copyright &y& Elsevier]

Abstract: A facile pathway to [RuCl2(η6-benzocrownether)]2 complexes is described and crystal structures of the complexes [RuCl2(η6-benzo-15-crown-5)]2 and [RuCl2(η6-dibenzo-18-crown-6)]2 are reported. The complexes were derivatised with (1S,2R)-2-amino-1,2-diphenylethanol and evaluated in the enantioselective transfer-hydrogenation of acetophenone. The effect of complexation of different alkaline metals (Na, K, Cs) within the crown on the selectivity and reaction rate was studied. Interaction of a sulfonated phosphine ligand with the crown was probed by NOESY-NMR and utilisation of the crownether to serve as an anchor for catalyst immobilisation was investigated. [Copyright &y& Elsevier]

The reaction of [RuCl3(AsPh3)2(MeOH)] with the dimeric complexes [(cod)RhCl]2, [(ppy)RhCl]2 (ppy=cyclometalated 2-phenylpyridine), [(cymene)RuCl2]2 and [Cp*MCl2]2 (M=Rh, Ir) has been investigated. The structure of the resulting products was shown to depend on the reaction partner. Whereas for the rhodium complexes [(cod)RhCl]2 and [(ppy)RhCl]2, heterobimetallic compounds with two halogeno-bridges were found, the reactions with the halfsandwich complexes [(cymene)RuCl2]2 and [Cp*MCl2]2 gave triply bridged products with concomitant formation of mononuclear [(π-ligand)MCl2(AsPh3)] side products. The new complexes were all characterized by single crystal X-ray analysis. [Copyright &y& Elsevier]

The water soluble ruthenium-p-cymene complexes [Ru(η6-p-cymene)X2]2 (X=Cl, Br, I or NCS), [Ru(η6-p-cymene)X2(pta)] (X=Cl, Br, I, or NCS; pta=1,3,5-triaza-7-phosphatricyclo[3.3.1.1]decane) and the tetraruthenium cluster [H4Ru4(η6-p-benzene)4]2+ have been prepared and their antimicrobial properties evaluated. They have been screened for antibacterial activity against Eschericia coli, Bascillus subtilis, Pseudomonas aeruginos, for antifungal activity against Candida albicans, Cladosporium resinae and Trichrophyton mentagrophytes and for antiviral activity against Herpes simplex and Polio viruses. The antimicrobial activity of these compounds does not appear to be correlated to DNA binding, but it could be due to specific interactions with proteins. The solid-state structure of the dimer complex [Ru(η6-p-cymene)Cl2]2, an important precursor complex in organometallic chemistry, is also reported. [Copyright &y& Elsevier]