Appraisal of the redox behaviour of the antimetastatic ruthenium(III) complex [ImH][RuCl(4)(DMSO)(Im)], NAMI-A

The imidazolium trans-tetrachloro(dimethylsulfoxide)imidazoleruthenate(III) complex [ImH][Ru(III)Cl(4)(DMSO)(Im)], NAMI-A, has shown an interesting antimetastatic activity. Since Ru(III) complexes are coordinatively more inert than the corresponding Ru(II) derivatives, an "activation by reduction" mechanism has been proposed to explain the biological activity of NAMI-A, thus acting as a pro-drug. We report here an electrochemical study on NAMI-A in aqueous solutions which emphasizes the structural and chemical consequences accompanying the easy Ru(III)/Ru(II) electron transfer (e.g., axial imidazole/water exchange in acidic solution in the short timescale of cyclic voltammetry followed by equatorial chloride/water exchange in the longer timescale of macroelectrolysis).     

Combined therapy of the antimetastatic compound NAMI-A and electroporation on B16F1 tumour cells in vitro

Ruthenium complex NAMI-A [ImH][trans-RuCl(4)(DMSO-S)Im] (Im = imidazole) is a potential chemotherapeutic drug in cancer treatment. Electroporation can be used to facilitate delivery of NAMI-A into cells. Suspension of B16F1 tumour cells from mouse melanoma in NAMI-A solution was exposed to a train of electric pulses. The effect of NAMI-A was determined by examining cell viability in clonogenic test. Our results show that electroporation increases the otherwise scarce in vitro effects of NAMI-A, i.e. reduces cell viability. At the conditions chosen for experiments 90% of cells survived in the presence of 1 microM NAMI-A, whereas in a combined treatment with 1 microM NAMI-A and electroporation only about 10% of cells survived.     

Synthesis and structural,spectroscopic, and electrochemical characterization of new ruthenium dimethyl sulfoxide nitrosyls

The reactivity of ruthenium(II)- and ruthenium(III)-chloride-dimethyl sulfoxide precursors and of the antimetastatic drug [ImH][trans-RuCl(4)(dmso-S)(Im)] (NAMI-A, Im = imidazole, dmso = dimethyl sulfoxide) toward NO was investigated. Treatment of [(dmso)(2)H][trans-RuCl(4)(dmso-S)(2)] and mer-RuCl(3)(dmso)(3) with gaseous NO yielded [(dmso)(2)H][trans-RuCl(4)(dmso-O)(NO)] (1) and mer,cis-RuCl(3)(dmso-O)(2)(NO) (2), respectively. Thus, coordination of the strong pi-acceptor NO induces a S to O linkage isomerization of the dmso trans to it to avoid competition for pi-electrons. In light-protected nitromethane solutions, complex 2 equilibrates slowly with the two isomers mer-RuCl(3)(dmso-S)(dmso-O)(NO) (3), with NO trans to Cl, and mer-RuCl(3)(dmso-S)(dmso-O)(NO) (4), with NO trans to dmso-O; the equilibrium mixture consists of ca. 64% 2, 3% 3, and 33% 4. Treatment of the Ru(II) precursor trans-RuCl(2)(dmso-S)(4) with gaseous NO in CH(2)Cl(2) solution yielded the nitrosyl-nitro derivative trans,cis,cis-RuCl(2)(dmso-O)(2)(NO)(NO(2)) (5). Finally, [(Im)(2)H][trans-RuCl(4)(Im)(NO)] (6) was prepared by treatment of [ImH][trans-RuCl(4)(dmso-O)(NO)] (1Im) with an excess of imidazole in refluxing acetone. The spectroscopic features are consistent with the [Ru(NO)](6) formulation for all complexes, that is, a diamagnetic Ru(II) nucleus bound to NO(+). Compounds 1, 2, 5, and 6 were characterized also by X-ray crystallography; they all show a linear nitrosyl group, with short Ru-NO bond distances consistent with a strong d(pi) --> pi NO back-bonding. An unusual inertness of O-bonded dmso was observed in compound 1. Complexes 1, 2, 3, 5, and 6 are all redox active in DMF solutions showing irreversible reductions whose peak potentials depend on the other ligands attached to the Ru metal center. The site of reduction is the NO(+) moiety. The reduced complexes are not stable and release a Cl(-) or NO(2)(-) ligand followed by the NO(*) radical. The chemical reactions following electron transfer are all fast (rate constant >100 s(-1) at 293 K). The Ru product species are not redox active within the DMF window.     

Exploiting soft and hard X-ray absorption spectroscopy to characterize metallodrug/protein interactions: the binding of [trans-RuCl4(Im)(dimethylsulfoxide)][ImH] (Im = imidazole) to bovine serum albumin

The reaction of bovine serum albumin (BSA) with [ trans-RuCl 4(Im)(dimethylsulfoxide)][ImH] (Im = imidazole) (NAMI-A), an experimental ruthenium(III) anticancer drug, and the formation of the respective NAMI-A/BSA adduct were investigated by X-ray absorption spectroscopy (XAS) at the sulfur and chlorine K-edges and at the ruthenium K- and L 3-edges. Ruthenium K and L 3-edge spectra proved unambiguously that the ruthenium center remains in the oxidation state +3 after protein binding. Comparative analysis of the chlorine K-edge XAS spectra of NAMI-A and NAMI-A/BSA, revealed that the chlorine environment is greatly perturbed upon protein binding. Only modest changes were observed in the sulfur K-edge spectra that are dominated by several protein sulfur groups. Overall, valuable information on the nature of this metallodrug/protein adduct and on the mechanism of its formation was gained; XAS spectroscopy turns out to be a very suitable method for the characterization of this kind of systems.     

Tuning of redox potentials for the design of ruthenium anticancer drugs -- an electrochemical study of [trans-RuCl(4)L(DMSO)](-) and [trans-RuCl(4)L(2)](-) complexes, where L = imidazole, 1,2,4-triazole, indazole

The electrochemical behavior of [trans-RuCl(4)L(DMSO)](-) (A) and [trans-RuCl(4)L(2)](-) (B) [L = imidazole (Him), 1,2,4-triazole (Htrz), and indazole (Hind)] complexes has been studied in DMF, DMSO, and aqueous media by cyclic voltammetry and controlled potential electrolysis. They exhibit one single-electron Ru(III)/Ru(II) reduction involving, at a sufficiently long time scale, metal dechlorination on solvolysis, as well as, in organic media, one single-electron reversible Ru(III)/Ru(IV) oxidation. The redox potential values are interpreted on the basis of the Lever's parametrization method, and particular forms of this linear expression (that relates the redox potential with the ligand E(L) parameter) are proposed, for the first time, for negatively (1-) charged complexes with the Ru(III/II) redox couple center in aqueous phosphate buffer (pH 7) medium and for complexes with the Ru(III/IV) couple in organic media. The E(L) parameter was estimated for indazole showing that this ligand behaves as a weaker net electron donor than imidazole or triazole. The kinetics of the reductively induced stepwise replacement of chloride by DMF were studied by digital simulation of the cyclic voltammograms, and the obtained rate constants were shown to increase with the net electron donor character (decrease of E(L)) of the neutral ligands (DMSO < indazole < triazole < imidazole) and with the basicity of the ligated azole, factors that destabilize the Ru(II) relative to the Ru(III) form of the complexes. The synthesis and characterization of some novel complexes of the A and B series are also reported, including the X-ray structural analyses of (Ph(3)PCH(2)Ph)[trans-RuCl(4)(Htrz)(DMSO)], [(Ph(3)P)(2)N][trans-RuCl(4)(Htrz)(DMSO)], (H(2)ind)[trans-RuCl(4)(Hind)(DMSO)], and [(Hind)(2)H][trans-RuCl(4)(Hind)(2)].     

Biotransformations of Anticancer Ruthenium(III) Complexes: An X‐Ray Absorption Spectroscopic Study

An anti‐metastatic drug, NAMI‐A ((ImH)[Ru^IIICl₄(Im)(dmso)]; Im=imidazole, dmso=S‐bound dimethylsulfoxide), and a cytotoxic drug, KP1019 ((IndH)[Ru^IIICl₄(Ind)₂]; Ind=indazole), are two Ru‐based anticancer drugs in human clinical trials. Their reactivities under biologically relevant conditions, including aqueous buffers, protein solutions or gels (e.g, albumin, transferrin and collagen), undiluted blood serum, cell‐culture medium and human liver (HepG2) cancer cells, were studied by Ru K‐edge X‐ray absorption spectroscopy (XAS). These XAS data were fitted from linear combinations of spectra of well‐characterised Ru compounds. The absence of XAS data from the parent drugs in these fits points to profound changes in the coordination environments of Ru^III. The fits point to the presence of Ru^IV/III clusters and binding of Ru^III to S‐donor groups, amine/imine and carboxylato groups of proteins. Cellular uptake of KP1019 is approximately 20‐fold higher than that of NAMI‐A under the same conditions, but it diminishes drastically after the decomposition of KP1019 in cell‐culture media, which indicate that the parent complex is taken in by cells through passive diffusion.     

A theoretical study on the hydrolysis process of the antimetastatic ruthenium(III) complex NAMI-A

A hydrolysis process of the anticancer drug ImH[trans-Ru(III)Cl4(DMSO)(Im)] (nicknamed NAMI-A; Im=imidazole, DMSO=dimethyl sulfoxide) has been studied by using density functional theory (DFT) method, and the aqueous solution effect has been considered and calculated by conductor-like polarizable calculation model (CPCM). The stationary points on the potential energy surfaces for the first and second hydrolysis steps (including two different paths) were fully optimized and characterized. The following was found: for the first hydrolysis process, the computed relative free energies DeltaG degrees (aq) and rate constant (k) in aqueous solution are 23.2 kcal/mol and 6.11x10(-5) s(-1), respectively, in satisfactory agreement with the experimental values; for the second hydrolysis step, some disagreement still exists, and thus more accurate solvent model needs to be designed and improved. On the basis of our present limited work, it can reasonably suggest that the hydrolysis process of NAMI-A perform mainly via the first hydrolysis step and then the path 1 of the second hydrolysis step. The theoretical results provide the structural properties as well as the detailed energy profiles for the mechanism of hydrolysis of NAMI-A, such results may assist in understanding the reaction mechanism of the anticancer drug with the biomolecular target.     

Control of ligand-exchange processes and the oxidation state of the antimetastatic Ru(III) complex NAMI-A by interactions with human serum albumin

The behaviour of the antimetastatic Ru(III) complex imidazolium [trans-RuCl?(1H-imidazole)(DMSO-S)] (NAMI-A) under physiological conditions and its interactions with human serum albumin (hsA) have been studied using electron paramagnetic resonance spectroscopy (EPR). In physiological buffer at pH 7.4, these experiments demonstrate that the DMSO ligand is replaced rapidly by water, and spectra from the subsequent formation of five other Ru(III) complexes show further aquation processes. Although EPR spectra from mono-nuclear Ru(III) complexes are visible after 24 h in buffer, a significant decrease in the overall signal intensity following the first aquation step is consistent with the formation of oxo-bridged Ru(III) oligomers. Incubation with hsA reveals very rapid binding to the protein via hydrophobic interactions. This is followed by coordination through ligand exchange with protein side chains, likely with histidine imidazoles and at least one other specific site. Similar behaviour is observed when the complex is incubated in human serum, indicating that hsA binding dominates speciation in vivo. The addition of ascorbic acid to NAMI-A in buffer leads to quantitative reduction, producing EPR-silent Ru(II) complexes. However, this process is prevented when the complex binds coordinatively to hsA. Together, these results demonstrate the key role that hsA plays in defining the species found in vivo following intravenous treatment with NAMI-A, through prevention of oligomerization and maintenance of the oxidation state, to give protein-bound mono-nuclear Ru(III) species.     

Pyridine analogues of the antimetastatic Ru(III) complex NAMI-A targeting non-covalent interactions with albumin

A series of pyridine-based derivatives of the antimetastatic Ru(III) complex imidazolium [trans-RuCl(4)(1H-imidazole)(DMSO-S)] (NAMI-A) have been synthesized along with their sodium-ion compensated analogues. These compounds have been characterized by X-ray crystallography, electron paramagnetic resonance (EPR), NMR, and electrochemistry, with the goal of probing their noncovalent interactions with human serum albumin (hsA). EPR studies show that the choice of imidazolium ligands and compensating ions does not strongly influence the rates of ligand exchange processes in aqueous buffer solutions. By contrast, the rate of formation and persistence of interactions of the complexes with hsA is found to be strongly dependent on the properties of the axial ligands. The stability of noncovalent binding is shown to correlate with the anticipated ability of the various pyridine ligands to interact with the hydrophobic binding domains of hsA. These interactions prevent the oligomerization of the complexes in solution and limit the rate of covalent binding to albumin amino acid side chains. Electrochemical studies demonstrate relatively high reduction potentials for these complexes, leading to the formation of Ru(II) species in aqueous solutions containing biological reducing agents, such as ascorbate. However, EPR measurements indicate that while noncovalent interactions with hsA do not prevent reduction, covalent binding produces persistent mononuclear Ru(III) species under these conditions.     

The hydrolysis process of the anticancer complex [ImH][trans-RuCl4(Im)2]: a theoretical study

A hydrolysis process of the anticancer drug [ImH][trans-RuCl4(Im)2] (ICR, Im=imidazole) has been investigated using density functional theory (DFT), and the aqueous solution effect has been considered and calculated by the conductor-like polarizable calculation model (CPCM). The stationary points on the potential energy surfaces for the first and second hydrolysis steps (including two different paths) were fully optimized and characterized. The results show that the computed values of free energy barriers DeltaG degrees (aq) and rate constants (k) in aqueous solution, in particular for the first hydrolysis step, are in excellent agreement with the experimental results. The analysis of electronic characteristics of species in the hydrolysis process suggests that the nucleophilic attack abilities (A) of hydrolysis products by biomolecular targets is in the sequence of A()相似文献   

Hydrolysis Mechanism of the NAMI-A-type Antitumor Complex (HL)[trans-RuCl4L(dmso-S)] (L=1-methyl-1,2,4-triazole)

The hydrolysis process of Ru(III) complex (HL)[trans-RuCl₄L(dmso-S)] (L=1-methyl-1,2,4-triazole and dmso-S=S-dimethyl sulfoxide) (1), a potential antitumor complex similar to the well-known antitumor agent (Him)[trans-RuCl₄L(dmso-S)(im)] (NAMI-A, im=imidazole), was investigated using density functional theory combined with the conductor-like polarizable continuum model approach. The structural characteristics and the detailed energy profiles for the hydrolysis processes of this complex were obtained. For the first hydrolysis step, complex 1 has slightly higher barrier energies than the reported anticancer drug NAMI-A, and the result is in accordance with the experimental evidence indicating larger half-life for complex 1. For the second hydrolysis step, the formation of cis-diaqua species is thermodynamic preferred to that of trans isomers. In addition, on the basis of the analysis of electronic characteristics of species in the hydrolysis process, the trend in nucleophilic attack abilities of hydrolysis products by pertinent biomolecules is revealed and predicted.     

Synthesis,X-ray diffraction structures,spectroscopic properties,and in vitro antitumor activity of isomeric (1H-1,2,4-triazole)Ru(III) complexes

Three ruthenium(III) complexes containing 1H-1,2,4-triazole (Htrz), viz., (H(2)trz)[cis-RuCl(4)(Htrz)(2)], 1, (H(2)trz)[trans-RuCl(4)(Htrz)(2)], 2, and (Ph(3)PCH(2)Ph)[trans-RuCl(4)(Htrz)(2)], 3, have been synthesized by reaction between RuCl(3) and excess of the triazole in 2.38 M HCl (1 and 2), while 3 was obtained by metathesis of 2 and [Ph(3)PCH(2)Ph]Cl in water. The products were characterized by IR, UV-vis, electrospray mass spectrometry, cyclic voltammetry, and X-ray crystallography (1 and 3). X-ray diffraction study revealed cis and trans arrangements of the triazole ligands in 1 and 3, correspondingly, and unprecedented monodentate coordination of the triazole through N2 and stabilization of its 4H tautomeric form, which is the disfavored one for the free triazole. The cytotoxicity of 1 and 2 has been assayed in three human carcinoma cell lines SW480, HT29 (colon carcinoma), and SK-BR-3 (mammary carcinoma). Both compounds exhibit antiproliferative activity in vitro. Time-dependent response of all three lines to 1 and 2 and a structure-activity relationship, i.e., higher activity of the trans-isomer 2 than that of cis-species 1, have been observed.     

En route to osmium analogues of KP1019: synthesis, structure, spectroscopic properties and antiproliferative activity of trans-[Os(IV)Cl4(Hazole)2

By controlled Anderson type rearrangement reactions complexes of the general formula trans-[Os(IV)Cl(4)(Hazole)(2)], where Hazole = 1H-pyrazole, 2H-indazole, 1H-imidazole, and 1H-benzimidazole, have been synthesized. Note that 2H-indazole tautomer stabilization in trans-[Os(IV)Cl(4)(2H-indazole)(2)] is unprecedented in coordination chemistry of indazole. The metal ion in these compounds possesses the same coordination environment as ruthenium(III) in (H(2)ind)[Ru(III)Cl(4)(Hind)(2)], where Hind = 1H-indazole, (KP1019), an investigational anticancer drug in phase I clinical trials. These osmium(IV) complexes are appropriate precursors for the synthesis of osmium(III) analogues of KP1019. In addition the formation of an adduct of trans-[Os(IV)Cl(4)(Hpz)(2)] with cucurbit[7]uril is described. The compounds have been comprehensively characterized by elemental analysis, EI and ESI mass spectrometry, spectroscopy (IR, UV-vis, 1D and 2D NMR), cyclic voltammetry, and X-ray crystallography. Their antiproliferative acitivity in the human cancer cell lines CH1 (ovarian carcinoma), A549 (nonsmall cell lung carcinoma), and SW480 (colon carcinoma) is reported.     

Replacement of chlorides with dicarboxylate ligands in anticancer active Ru(II)-DMSO compounds: a new strategy that might lead to improved activity

A series of new Ru(II)-DMSO complexes containing dicarboxylate ligands (dicarb), namely, oxalate (ox), malonate (mal), methylmalonate (mmal), dimethylmalonate (dmmal), and succinate (suc), have been synthesized and structurally characterized. These compounds were prepared from the known Ru(II)-Cl-DMSO anticancer complexes cis,fac-[RuCl2(DMSO-S)3(DMSO-O)] (1) and trans-[RuCl2(DMSO-S)4] (2) and from the chloride-free precursor fac-[Ru(DMSO-S)3(DMSO-O)3][CF3SO3]2 (3), with the aim of assessing how the nature of the anionic ligands influences the biological activity of these species. Basically, the investigated ligands can be divided into two groups. The reaction of either 1 or 2 with K2(dicarb) (dicarb = ox, mal, mmal) yielded preferentially the mononuclear species [K]fac-[RuCl(DMSO-S)3(eta2-dicarb)] (dicarb = mal, 6; mmal, 9; ox, 14) that contains a chelating dicarboxylate unit and a residual chloride. Likewise, when 3 was used as a precursor, the neutral mononuclear species fac-[Ru(DMSO-O)(DMSO-S)3(eta2-dicarb)] (dicarb = mal, 7; mmal, 10; ox, 16), which contains a DMSO-O ligand in the place of Cl-, was obtained. On the contrary, K2(suc) and K2(dmmal) yielded preferentially the dinuclear species [fac-Ru(DMSO-S)3(H2O)(mu-dicarb)]2 (dicarb = dmmal, 11; suc, 13), with two bridging dicarboxylate moieties. The two water molecules in anti geometry have strong intramolecular H-bonding with the non-coordinated oxygen atoms of the carboxylate groups. The solid-state X-ray structural data showed that the preferential binding mode of the investigated dicarboxylates, either bridging (mu) or chelating (eta2), is dictated mainly by steric reasons. Oxalate, unlike the other dicarboxylates, has also the bridging bis-chelate (eta4,mu) coordination mode available: this was found in the dinuclear species [{fac-RuCl(DMSO-S)3}2(eta4,mu-ox)] (15) and [{fac-Ru(DMSO-O)(DMSO-S)3}2(eta4,mu-ox)][CF3SO3]2 (17). We also isolated the unprecedented neutral metallacycle, [fac-Ru(DMSO-S)3(eta3,mu-ox)]4 (18), in which each oxalate unit has one unbound oxygen atom. The new complexes were thoroughly characterized by 1-D (1H and 13C) and 2-D (H-H- COSY and HMQC) NMR spectroscopy in solution and by IR spectroscopy in the solid state. The molecular structures of 10 compounds, 6-11, 13, 15, 17, and 18, were determined by X-ray crystallography. The behavior of selected complexes in aqueous solution was investigated by 1H NMR spectroscopy.     

Osmium NAMI-A analogues: synthesis, structural and spectroscopic characterization, and antiproliferative properties

The osmium(III) complex [(DMSO)2H][trans-OsIIICl4(DMSO)2] (1) has been prepared via stepwise reduction of OsO4 in concentrated HCl using N2H(4).2HCl and SnCl(2).2H2O in DMSO. 1 reacts with a number of azole ligands, namely, indazole (Hind), pyrazole (Hpz), benzimidazole (Hbzim), imidazole (Him), and 1H-1,2,4-triazole (Htrz), in organic solvents, affording novel complexes (H2ind)[OsIIICl4(Hind)(DMSO)] (2), (H2pz)[OsIIICl4(Hpz)(DMSO)] (3), (H2bzim)[OsIIICl4(Hbzim)(DMSO)] (4), (H2im)[OsIIICl4(Him)(DMSO)] (6), and (H2trz)[OsIIICl4(Htrz)(DMSO)] (7), which are close analogues of the antimetastatic complex NAMI-A. Metathesis reaction of 4 with benzyltriphenylphosphonium chloride in methanol led to the formation of (Ph3PCH2Ph)[OsIIICl4(Hbzim)(DMSO)] (5). The complexes were characterized by IR, UV-vis, ESI mass spectrometry, 1H NMR spectroscopy, cyclic voltammetry, and X-ray crystallography. In contrast to NAMI-A, 2-4, 6, and 7 are kinetically stable in aqueous solution and resistant to hydrolysis. Surprisingly, they show reasonable antiproliferative activity in vitro in two human cell lines, HT-29 (colon carcinoma) and SK-BR-3 (mammary carcinoma), when compared with analogous ruthenium compounds. Structure-activity relationships and the potential of the prepared complexes for further development are discussed.     

α-Synuclein as a Target for Metallo-Anti-Neurodegenerative Agents

The unique thermodynamic and kinetic coordination chemistry of ruthenium allows it to modulate key adverse aggregation and membrane interactions of α-synuclein (α-syn) associated with Parkinson's disease. We show that the low-toxic Ru^III complex trans-[ImH][RuCl₄(Me₂SO)(Im)] (NAMI-A) has dual inhibitory effects on both aggregation and membrane interactions of α-syn with submicromolar affinity, and disassembles pre-formed fibrils. NAMI-A abolishes the cytotoxicity of α-syn towards neuronal cells and mitigates neurodegeneration and motor impairments in a rat model of Parkinson's. Multinuclear NMR and MS analyses show that NAMI-A binds to residues involved in protein aggregation and membrane binding. NMR studies reveal the key steps in pro-drug activation and the effect of activated NAMI-A species on protein folding. Our findings provide a new basis for designing ruthenium complexes which could mitigate α-syn-induced Parkinson's pathology differently from organic agents.     

Redox behavior of tumor-inhibiting ruthenium(III) complexes and effects of physiological reductants on their binding to GMP

Biotransformation of ruthenium(III) anticancer complexes as hypothesized in the activation-by-reduction theory is the central topic of the present paper. The redox behavior of tetrachlorobis(azole)ruthenate(III)-type complexes was studied by NMR spectroscopy and square wave voltammetry. The influence of reducing agents on the binding behavior toward the DNA-modeling nucleotide GMP was determined by capillary electrophoresis, accompanied by identification of arising peaks by online coupling to electrospray ionization mass spectrometry. The determination of redox potentials revealed that the biologically relevant reductants ascorbic acid and glutathione are capable of reducing the studied Ru(III) complexes under physiological conditions. Characteristic differences in reduction kinetics dependent on the pH value can be explained by higher reduction strength of ascorbic acid and glutathione at higher pH compared to the pH-independent redox response of ruthenium(III) complexes. Binding behavior of (H2ind)[trans-RuCl4(Hind)2] (Hind = 1H-indazole) toward GMP was found to be increased upon addition of two equivalents of glutathione but not of ascorbic acid. In contrast, only a minor influence on the GMP-binding under reductive conditions was found for (H2im)[trans-RuCl4(Him)2] (KP418, Him = 1H-imidazole).     

Platinum participation in the hydrogenation of phenylacetylene by Ru5(CO)15(C)[Pt(PBu(t)3)

The hydride and PhC2H complexes, Ru5(CO)14(mu6-C)[Pt(PBut3)](mu-H)2, 2, and Ru5(CO)13(mu5-C)(PhC2H)[Pt(PBut3)], 3, were obtained from the reactions of Ru5(CO)15(C)[Pt(PBut3)], 1, with hydrogen and PhC2H, respectively. Styrene was formed catalytically when hydrogen and PhC2H were allowed to react with 3 in combination, and the complex Ru5(CO)12(mu5-C)[PtPBut3](PhC2H)(mu-H)2, 4, containing both hydrides and a PhC2H ligand was formed. The catalysis is promoted by the presence of the platinum atom in the complexes.     

Efficient oxidation of cysteine and glutathione catalyzed by a dinuclear areneruthenium trithiolato anticancer complex

The highly cytotoxic diruthenium complex [(p-MeC(6)H(4)Pr(i))(2)Ru(2)(SC(6)H(4)-p-Me)(3)](+) (1), water-soluble as the chloride salt, is shown to efficiently catalyze oxidation of the thiols cysteine and glutathione to give the corresponding disulfides, which may explain its high in vitro anticancer activity.     

Oxidation of linear trinuclear ruthenium complexes [Ru(3)(dpa)(4)Cl(2)] and [Ru(3)(dpa)(4)(CN)(2)]: synthesis, structures, electrochemical and magnetic properties

The neutral, monocationic, and dicationic linear trinuclear ruthenium compounds [Ru(3)(dpa)(4)(CN)(2)], [Ru(3)(dpa)(4)(CN)(2)][BF(4)], [Ru(3)(dpa)(4)Cl(2)][BF(4)], and [Ru(3)(dpa)(4)Cl(2)][BF(4)](2) (dpa=the anion of dipyridylamine) have been synthesized and characterized by various spectroscopic techniques. Cyclic voltammetric and spectroelectrochemical studies on the neutral and oxidized compounds are reported. These compounds undergo three successive metal-centered one-electron-transfer processes. X-ray structural studies reveal a symmetrical Ru(3) unit for these compounds. While the metal--metal bond lengths change only slightly, the metal--axial ligand lengths exhibit a significant decrease upon oxidation of the neutral complex. The electronic configuration of the Ru(3) unit changes as the axial chloride ligands are replaced by the stronger "pi-acid" cyanide axial ligands. Magnetic measurements and (1)H NMR spectra indicate that [Ru(3)(dpa)(4)Cl(2)] and [Ru(3)(dpa)(4)Cl(2)][BF(4)](2) are in a spin state of S=0 and [Ru(3)(dpa)(4)Cl(2)][BF(4)], [Ru(3)(dpa)(4)(CN)(2)], and [Ru(3)(dpa)(4)(CN)(2)][BF(4)] are in spin states of S=1/2, 1, and 3/2, respectively. These results are consistent with molecular orbital (MO) calculations.