Synthesis and antiamoebic activity of new cyclooctadiene ruthenium(II) complexes with 2-acetylpyridine and benzimidazole derivatives

Reaction of [Ru(eta4-C8H12) (CH3CN)2 Cl2] with 2-(2-pyridyl) benzimidazole or Schiff bases derived from 2-acetylpyridine and S-methyldithiocarbazate, S-benzyldithiocarbazate and thiosemicarbazide leads to form new complexes of the type [Ru(eta4-C8H12)(L)Cl2] (where L=ligand). In vitro, most of the compounds exhibited potent activity and the Ru derivatives 1a [Ru(eta4-C8H12)(2-Acpy-SMDT)Cl2], 2a [Ru(eta4-C8H12)(2-Acpy-SBDT)Cl2] and 3a [Ru(eta4-CsH12)(2-Acpy-TSC)Cl2] were found more active than metronidazole against (HK-9) strain of Entamoeba histolytica.     

Structure-dependent in vitro cytotoxicity of the isomeric complexes [Ru(L)2Cl2] (L=o-tolylazopyridine and 4-methyl-2-phenylazopyridine) in comparison to [Ru(azpy)2Cl2]

The dichlorobis(2-phenylazopyridine)ruthenium(II) complexes, [Ru(azpy)(2)Cl(2)], are under renewed investigation due to their potential anticancer activity. The three most common isomers alpha-, beta- and gamma-[RuL(2)Cl(2)] with L= o-tolylazopyridine (tazpy) and 4-methyl-2-phenylazopyridine (mazpy) (alpha indicating the coordinating Cl, N(pyridine) and Nazo atoms in mutual cis, trans, cis positions, beta indicating the coordinating Cl, N(pyridine) and Nazo atoms in mutual cis, cis, cis positions, and gamma indicating the coordinating Cl, N(pyridine) and Nazo atoms in mutual trans, cis, cis positions) are synthesized and characterized by NMR spectroscopy. The molecular structures of gamma-[Ru(tazpy)(2)Cl(2)] and alpha-[Ru(mazpy)(2)Cl(2)] are determined by X-ray diffraction analysis. The IC(50) values of the geometrically isomeric [Ru(tazpy)(2)Cl(2)] and [Ru(mazpy)(2)Cl(2)] complexes compared with those of the parent [Ru(azpy)(2)Cl(2)] complexes are determined in a series of human tumour cell lines (MCF-7, EVSA-T, WIDR, IGROV, M19, A498 and H266). These data unambiguously show for all complexes the following trend: the alpha isomer shows a very high cytotoxicity, whereas the beta isomer is a factor 10 less cytotoxic. The gamma isomers of [Ru(tazpy)(2)Cl(2)] and [Ru(mazpy)(2)Cl(2)] display a very high cytotoxicity comparable to that of the gamma isomer of the parent compound [Ru(azpy)(2)Cl(2)] and to that of the alpha isomer. These biological data are of the utmost importance for a better understanding of the structure-activity relationships for the isomeric [RuL(2)Cl(2)] complexes.     

Synthesis and anti-amoebic activity of gold(I), ruthenium(II), and copper(II) complexes of metronidazole

A series of Au, Ru, and Cu complexes of metronidazole (= [1-(2-hydroxyethyl)-2-methyl-5-nitro-1H-imidazole; 1) were prepared as highly potent anti-amoebic drugs. The complexes [Au(PPh3)(1)]PF6 (2), [Ru(1)2(Cl)2(H2O)2] (3), and [Cu(1)2(mu-Cl)(H2O)]2Cl2 (4) were readily synthesized from [Au(PPh3)Cl], RuCl3 x 3 H2O, and CuCl2 x 2 H2O, respectively. All complexes were thoroughly characterized by IR, UV/VIS, 1H-NMR, FAB-MS, elemental and thermogravimetric analyses, and, in the case of 4, also by X-ray crystallography (Fig. 1). All complexes were evaluated in vitro as growth inhibitors of Entamoeba histolytica (HM1:IMSS strain). Their IC50 values were in the range of 0.10-0.51 microM (Table 2), which makes these drugs, especially the Cu(II) complex 4, considerably more potent than uncomplexed metronidazole (1; IC50 = 1.81 microM), the current standard drug for the worldwide treatment of amoebiasis.     

Synthesis,molecular structure,solution equilibrium,and antiproliferative activity of thioxotriazoline and thioxotriazole complexes of copper II and palladium II

Preparations of copper(II) and palladium(II) complexes of 4-amino-5-methylthio-3-(2-pyridyl)-1,2,4-triazole (L(1)) and the copper(II) complex of 1,4-dihydro-4-amino-3-(2-pyridyl)-5-thioxo-1,2,4-triazole (HL) are described. These complexes have been characterized by means of spectroscopy and microanalysis. Molecular structures of HL (1), [CuCl(2)(H(2)L)]Cl.2H(2)O (2a), cis-[CuCl(2)(L(1))] (3), and cis-[PdCl(2)(L(1))] (4) have been determined by single-crystal X-ray diffraction. The HL ligand acts as a N,S bidentate through the thioxo moiety and the exo-amino group whilst the ligand L(1) forms N,N coordination complexes through the pyridine and triazole nitrogen atoms. Speciation in solution of the systems Cu/HL and Cu/L(1) have been determined by means of potentiometry and spectrophotometry as well as for the Cu/L(1)/A (HA=glycine) system in order to determine species present at physiological pH. Antiproliferative activity of these complexes and their ligands was evaluated, using the AlamarBlue Assay, on normal human fibroblasts (HF) and human fibrosarcoma tumor (HT1080) cells. The copper compounds cis-[CuCl(2)(H(2)L)]Cl and cis-[CuCl(2)(L(1))] exerted significant antiproliferative activity of both normal and neoplastic cells; although dose-response experiments revealed that the HT1080 cell line was more sensitive to the tested drugs than normal fibroblasts.     

Metal–metal interactions in linear tri-, penta-, hepta-, and nona-nuclear ruthenium string complexes

Density functional theory (DFT) methodology was used to examine the structural properties of linear metal string complexes: [Ru(3)(dpa)(4)X(2)] (X = Cl(-), CN(-), NCS(-), dpa = dipyridylamine(-)), [Ru(5)(tpda)(4)Cl(2)], and hypothetical, not yet synthesized complexes [Ru(7)(tpta)(4)Cl(2)] and [Ru(9)(ppta)(4)Cl(2)] (tpda = tri-α-pyridyldiamine(2-), tpta = tetra-α-pyridyltriamine(3-), ppta = penta-α-pyridyltetraamine(4-)). Our specific focus was on the two longest structures and on comparison of the string complexes and unsupported ruthenium backboned chain complexes, which have weaker ruthenium-ruthenium interactions. The electronic structures were studied with the aid of visualized frontier molecular orbitals, and Bader's quantum theory of atoms in molecules (QTAIM) was used to study the interactions between ruthenium atoms. The electron density was found to be highest and distributed most evenly between the ruthenium atoms in the hypothetical [Ru(7)(tpta)(4)Cl(2)] and [Ru(9)(ppta)(4)Cl(2)] string complexes.     

Hydrolysis and cytotoxic properties of osmium(II)/(III)-DMSO-azole complexes. Short communication

The antiproliferative properties of the osmium(II) complexes cis,fac-[Os(II)Cl(2)(DMSO)(3)(L)] and trans,cis,cis-[Os(II)Cl(2)(DMSO)(2)(L)(2)] (L = 1H-pyrazole, 1H-imidazole) were studied in three human cancer cell lines, namely 41M (ovary), SK-BR-3 (breast), and SW480 (colon). Their activities were compared with those of osmium(III) and ruthenium(III) NAMI-A type complexes on HT-29 (colon) and SK-BR-3 cancer cell lines. While IC(50) values of all the Os(II) complexes were found to be >1000 microM in all cell lines, Os and Ru-NAMI-A type complexes showed remarkable antiproliferative activity. The marginal in vitro cytotoxicity of the Os(II) compounds is presumably attributed to their resistance to hydrolysis. However, the Os-NAMI-A complexes, which are also kinetically stable in aqueous solution, showed reasonable antiproliferative activity in vitro when compared with the analogous Ru compounds and with the Os(II)-DMSO-azole species, indicating that hydrolysis might be not a prerequisite for the antitumor activity of Os-NAMI-A type complexes.     

Synthesis and structure of cycloruthenated carbonyl complexes and their emission, redox and biological properties

An interesting series of mononuclear organoruthenium complexes of formulation [Ru(CO)(PPh3)2(ap-R)] (where ap-R = -H, -Cl, -Me, -OMe, -OEt) have been synthesized from the reaction of five 2-(arylazo)phenol ligands with ruthenium(II) precursor [RuH(Cl)(CO)(PPh3)3] in benzene under reflux. The 2-(arylazo)phenolate ligands behave as dianionic tridentate ligand and are coordinated to ruthenium through C, N and O by dissociation of the phenolic and phenyl proton at the ortho position of the phenyl ring forming two five-membered chelate rings. These complexes have been characterized by elemental analysis, FT-IR, 1H NMR and UV-visible spectroscopy. In dichloromethane solution all the metal complexes exhibit characteristic metal-to-ligand charge transfer (MLCT) absorption and emission bands in the visible region. The structures of [Ru(CO)(PPh3)2(ap-H)] and [Ru(CO)(PPh3)2(ap-Cl)] have been determined by X-ray crystallography. Cyclic voltammetric data of all the complexes show a Ru(III)/Ru(II) oxidation and reduction Ru(II)/Ru(I) within the range 0.74-0.84 V and -0.38 to -0.50 V vs saturated calomel electrode (SCE) respectively. The potentials are observed with respect to the electronic nature of substituents (R) in the 2-(arylazo)phenolate ligands. Further, the free ligands and their ruthenium complexes have also been screened for their antibacterial and antifungal activities, which have shown great promise in inhibiting the growth of both gram +ve and gram -ve bacteria Staphylococcus aureus and Escherichia coli and fungus Candida albicans and Aspergillus niger. These results made it desirable to delineate a comparison between free ligands and their complexes.     

Synthesis, characterization, EXAFS investigation and antibacterial activities of new ruthenium(III) complexes containing tetradentate Schiff base

A series of new hexa-coordinated ruthenium(III) complexes of the type [Ru(X)(2-atmp-ba)(EPh3)] (where H2-2-atmp-ba=N,N'-bis(2-aminothiophenol)benzoylacetone; X=Cl or Br; E=P or As) have been prepared by reacting [RuX3(EPh3)3] (where X=Cl or Br; E=P or As) with tetradentate Schiff base ligand (H2-2-atmp-ba) in 1:1 molar ratio. The complexes have been characterized by elemental analyses, Infra red, electronic, electron paramagnetic resonance spectroscopy and cyclic voltammetry. In order to confirm the coordination and structure of the complexes extended X-ray absorption fine structure spectroscopy (EXAFS) studies have been carried out. Based on the above data, an octahedral structure has been confirmed for the complexes. The new complexes were also screened for their antibacterial properties.     

Synthesis, characterisation and antiamoebic activity of new thiophene-2-carboxaldehyde thiosemicarbazone derivatives and their cyclooctadiene Ru(II) complexes

Reaction of new thiosemicarbazones (1-4) derived from thiophene-2-carboxaldehyde and cycloalkylaminothiocarbonylhydrazine with [Ru(eta(4)-C8H12)(CH3CN)2Cl2] leads to form complexes (1a-4a) of the type [Ru(eta(4)-C8H12)(TSC)Cl2] (where TSC=thiosemicarbazone). All the compounds have been characterised by elemental analysis, IR, 1H NMR, electronic spectra and thermogravimetric analysis. It is concluded that the thionic sulphur and the azomethine nitrogen atom of the ligands are bonded to the metal ion. In vitro antiamoebic screening against (HK-9) strain of Entamoeba histolytica indicated that the Ru(II) complexes of thiophene-2-carboxaldehyde thiosemicarbazones were found more active than the thiosemicarbazones.     

The effects of ruthenium tetraammine compounds on vascular smooth muscle.

The time course of the relaxation effect induced by a single dose (3 x 10(-6) mol/L) of trans-[Ru(NH3)4L(NO)]3+ (L=nic, 4-pic, py, imN, P(OEt)3, SO(3)(2-), NH3, and pz) species and sodium nitroprusside (4 x 10(-9) mol/L) was studied in aortic rings without endothelium and pre-contracted with noradrenaline (1 x 10(-6) mol/L). All the compounds induced a relaxing effect in the aortic rings, but the intensity and time of relaxation were different. Only the species where L=py, 4-pic, and P(OEt)3 were able to induce 100% (99-100%) of the relaxing effect during the assay. trans-[Ru(NH3)4(L)(NO)]3+ (L=SO(3)(2-) and NH3) showed the lowest relaxing effect (36 and 37%, respectively) when compared with the other compounds. Relationship was observed between the time corresponding to half of the maximum relaxation intensity observed and, respectively, k-NO, E0'[Ru(NO)]3+/[Ru(NO)]2+ in trans-[Ru(NH3)4(L)(NO)]3+ species and E0'Ru(III)/Ru(II) in trans-[Ru(NH3)4(L)(H2O)]3+ ions. These relationships strongly suggested that the NO liberation from the reduced nitrosyl complexes was responsible for the observed relaxation.     

Synthesis, characterization and DNA binding studies of two mixed ligand complexes of ruthenium(II)

Two mixed ligand complexes [Ru(bpy)(2)(DMHBT)]Cl(2)(1) and [Ru(phen)(2)(DMHBT)]Cl(2) (2) (where DMHBT is 11,13-dimethyl-13H-4,5,9,11,14-hexaaza-benzo[b]triphenylene-10,12-dione) have been synthesized and characterized by electrospray ionization (ESI) mass, (1)H-(1)H correlation spectroscopy (COSY), electronic spectroscopy, fluorescence spectroscopy and cyclic voltammetry. Spectroscopic titration and viscosity changes of calf thymus (CT)-DNA in the presence of incremental amount of complexes 1 and 2 clearly demonstrate that both these complexes bind intercalatively to DNA, with binding constant 2.87+/-0.20 x 10(4)M(-1) and 1.01+/-0.20 x 10(5)M(-1) for complexes 1 and 2, respectively. All the experimental evidences suggest that the ancillary ligand 2,2'-bipyridine (bpy) and 1,10-phenanthroline (phen) influences the intercalative binding of these complexes to DNA.     

Synthesis, antitumor activity and structure-activity relationships of a series of Ru(II) complexes

A series of octahedral Ru(II) polypyridyl complexes, [Ru(phen)(2)L](2+) (L=R-PIP and PIP=2-phenylimidazo[4,5-f][1,10]phenanthroline) were synthesized and characterized by elementary analysis, (1)H NMR and ES-MS, as well as UV-visible spectra and emission spectra. The antitumor activities of these complexes and their corresponding ligands were investigated against mouse leukemia L1210 cells, human oral epidermoid carcinoma KB cells, human promyelocytic leukemia cells (HL-60) and Bel-7402 liver cancer cells by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. It was found that the complexes [Ru(phen)(2)L](2+) (L=R-PIP) exert rather potent activities against all of these cell lines, especially for the KB cells (IC(50)=4.7+/-1.3 microM). The binding affinities of these Ru(II) complexes to CT-DNA (calf thymus DNA), as well as the DNA-unwinding properties on supercoiled pBR322 DNA were also investigated. The results showed that these Ru(II) polypyridyl complexes not only had an excellent DNA-binding property but also possessed a highly effective DNA-photocleavage ability. The structure-activity relationships and antitumor mechanism were also carefully discussed.     

Synthesis, structure and properties of di- and mononuclear ruthenium(III) complexes with N-(benzoyl)-N′-(salicylidene)hydrazine and its derivatives

The reactions of [Ru(PPh₃)₃Cl₂], N-(benzoyl)-N′-(5-R-salicylidene)hydrazines (H₂bhsR, R = H, OCH₃, Cl, Br and NO₂) and triethylamine (1:1:2 mole ratio) in methanol afford mononuclear ruthenium(III) complexes having the general formula trans-[Ru(bhsR)(PPh₃)₂Cl]. In the case of R = H, a dinuclear ruthenium(III) complex of formula [Ru₂(μ-OCH₃)₂(bhsH)₂(PPh₃)₂] has been isolated as a minor product. The complexes are characterized by elemental analysis, magnetic, spectroscopic and electrochemical measurements. The crystal structures of the dinuclear complex and two mononuclear complexes have been determined. In the dinuclear complex, each metal centre is in distorted octahedral NO₄P coordination sphere constituted by the two bridging methoxide groups, one PPh₃ molecule and the meridionally spanning phenolate-O, imine-N and amide-O donor bhsH²⁻. The terminal PPh₃ ligands are trans to each other. In the mononuclear complexes, bhsR²⁻ and the chlorine atom form an NO₂Cl square-plane around the metal centre and the P-atoms of the two PPh₃ molecules occupy the remaining two axial sites to complete a distorted octahedral NO₂ClP₂ coordination sphere. All the complexes display ligand-to-metal charge transfer bands in the visible region of the electronic spectra. The cryomagnetic measurements reveal the antiferromagnetic character of the diruthenium(III) complex. The low-spin mononuclear ruthenium(III) complexes as well as the diruthenium(III) complex display rhombic EPR spectra in frozen solutions. All the complexes are redox active in CH₂Cl₂ solutions. Two successive metal centred oxidations at 0.69 and 1.20 V (versus Ag/AgCl) are observed for the dinuclear complex. The mononuclear complexes display a metal centred reduction in the potential range −0.53 to −0.27 V. The trend in these potential values reflects the polar effect of the substituents on the salicylidene moiety of the tridentate ligand.     

Pt(II) complexes with N-(3-pyridyl)-2-(4-(trifluoromethyl)phenyl)diazenecarboxamide and their reactions with glutathione

The reaction between [PtCl(dmso)(en)]Cl (dmso=dimethyl sulfoxide, en=ethylenediamine) and N-(3-pyridyl)-2-(4-(trifluoromethyl)phenyl)diazenecarboxamide (L) was studied using multinuclear NMR spectroscopy. The water-soluble complexes [PtCl(en)(L-N1)](+) (1) and [Pt(en)(L-N1)(2)](2+) (2) were isolated and their reactions with glutathione (GSH) were investigated to assess the oxidation properties of coordinated L. Both species 1 and 2 oxidized GSH to GSSG, while the reduced form of L (semicarbazide, SL) remained coordinated to Pt(2+). In complex 1 the labile chloride ion was substituted by the thiol moiety of GSH, which gave rise to the release of en in excess GSH over a period of 7 days. Complexes [PtCl(dmso)(en)]Cl, 1, 2 and ligand L were tested against T24 bladder carcinoma cells. Ligand L and complexes 1 and 2 showed higher cytotoxicity than [PtCl(dmso)(en)]Cl.     

Half-sandwich Ru II[9]aneS3 complexes structurally similar to antitumor-active organometallic piano-stool compounds: preparation, structural characterization and in vitro cytotoxic activity

The preparation, structural characterization, and chemical behavior in aqueous solution of a series of new Ru[9]aneS3 half-sandwich complexes of the type [Ru([9]aneS3)Cl(NN)][CF3SO3] and [Ru([9]aneS3)(dmso-S)(N-N)][CF3SO3]2 (5-15, NN=substituted bpy or 2x1-methylimidazole) are described. The X-ray structures of [Ru([9]aneS3)Cl(3,3'-H2dcbpy)][CF3SO3] (9) (3,3'-H2dcbpy=3,3'-dicarboxy-2,2'-bipyridine), [Ru([9]aneS3)Cl(4,4'-dmobpy)][CF3SO3] (13) (4,4'-dmobpy=4,4'-dimethoxy-2,2'-bipyridine), and [Ru([9]aneS3)Cl(1-MeIm)2][CF3SO3] (15) (1-MeIm=1-methylimidazole) were also determined. The new compounds are structurally similar to anticancer-active organometallic half-sandwich complexes of formula [Ru(eta6-arene)Cl(NN)][PF6]. Three chloro compounds (5, 9, 15) were tested in vitro for cytotoxic activity against two human cancer cell lines in comparison with the previously described [Ru([9]aneS3)Cl(en)][CF3SO3] (1, en=ethylenediamine), [Ru([9]aneS3)Cl(bpy)][CF3SO3] (2), and with their common dmso precursor [Ru([9]aneS3)Cl(dmso-S)2][CF3SO3] (3). Only the ethylenediamine complex 1 showed some antiproliferative activity, ca. one order of magnitude lower than the reference organometallic half-sandwich compound RM175 that contains biphenyl instead of [9]aneS3. This compound was further tested against a panel of human cancer cell lines (including one resistant to cisplatin).     

Proton-linked bi- and tri-metallic gold cyanide complexes observed by ESI-MS spectrometry

Electrospray ionization spectra of potential cyanide-containing gold-drug metabolites revealed additional, weak, unanticipated peaks at approximately twice the mass of the gold(I) and gold(III) cyanide complexes. The exact masses correspond to proton-linked bimetallic complexes, [H[Au(CN)(m)](2)](-), (m=2,4). Further investigation revealed a total of 12 examples, including trimetallic complexes, [H(2)[Au(CN)(m)](3)](-); mixed species with two complexes, [H[Au(CN)(2)][Au(CN)(4)]](-); and thiolato species, [H[(RS)Au(CN)(3)](2)](-). trans-[AuX(2)(CN)(2)Cl(2)](-) and trans-[AuX(2)(CN)(2)Br(2)](-) generated (35)Cl/(37)Cl and (79)Br/(81)Br isotopic patterns for the protonated bi- and tri-metallic analogues which were in good agreement with the presence of four or six halide ligands, respectively. Concentration-dependent studies demonstrated that the signals are independent of the solution concentrations of mono-metallic precursors, suggesting formation in the gas phase during or following droplet desolvation.     

Mixed ligand complexes of platinum(II) and palladium(II) with cytokinin-derived compounds Bohemine and Olomoucine: X-ray structure of [Pt(BohH+-N7)Cl(3)].9/5H2O [Boh=6-(benzylamino)-2-[(3-(hydroxypropyl)-amino]-9-isopropylpurine,Bohemine

The new square-planar Pt(II) and Pd(II) complexes with cytokinin-derived compounds Bohemine and Olomoucine, having the formulae [Pt(BohH(+))Cl(3)].H(2)O (1), [Pt(Boh)(2)Cl(2)].3H(2)O (2), [Pt(Boh-H)Cl(H(2)O)(2)].H(2)O (3), [Pt(OloH(+))Cl(3)].H(2)O (4), [Pd(BohH(+))Cl(3)].H(2)O (5), [Pd(Boh)Cl(2)(H(2)O)] (6), [Pd(Boh-H)Cl(H(2)O)].EtOH (7) and [Pd(OloH(+))Cl(3)].H(2)O (8), where Boh=6-(benzylamino)-2-[(3-(hydroxypropyl)amino]-9-isopropylpurine and Olo=6-(benzylamino)-2-[(2-(hydroxyethyl)amino]-9-methylpurine, have been synthesized. The complexes have been characterized by elemental analyses, IR, FAB+ mass, 1H, 13C and 195Pt NMR spectra, and conductivity data. The molecular structure of the complex [Pt(BohH(+)-N7)Cl(3)].9/5H(2)O has been determined by an X-ray diffraction study. Results from physical studies show that both Bohemine and Olomoucine are coordinated to transition metals through the N(7) atom of purine ring in all the complexes. The prepared compounds have been tested in vitro for their possible cytotoxic activity against G-361 (human malignant melanoma), HOS (human osteogenic sarcoma), K-562 (human chronic myelogenous leukemia) and MCF-7 (human breast adenocarcinoma) cell lines and IC(50) values have been also determined for all the complexes. IC(50) values estimated for the Pt(II)-Bohemine complexes (2.1-16 microM) allow us to conclude that they could find utilization in antineoplastic therapy. Thus, from a pharmacological point of view, Pt(II) complexes of Bohemine may represent compounds for a new class of antitumor drugs.     

Highly cytotoxic trithiophenolatodiruthenium complexes of the type [(η6-p-MeC6H4Pr i )2Ru2(SC6H4-p-X)3]+: synthesis, molecular structure, electrochemistry, cytotoxicity, and glutathione oxidation potential

A series of cationic dinuclear p-cymene ruthenium trithiophenolato complexes of the type [(η(6)-p-MeC(6)H(4)Pr(i))(2)Ru(2)(SC(6)H(4)-p-X)(3)](+) (1 X is H, 2 X is Me, 3 X is Ph, 4 X is Br, 5 X is OH, 6 X is NO(2), 7 X is OMe, 8 X is CF(3), 9 X is F, 10 X is Pr(i), 11 X is Bu(t)) have been synthesized from the reaction of [(η(6)-p-MeC(6)H(4)Pr(i))RuCl(2)](2) with the corresponding thiol, isolated as the chloride salts, and further studied for their electrochemical properties, cytotoxicity towards human ovarian cancer cells, and catalytic activity for glutathione (GSH) oxidation. Complex 1 was also compared with the benzene and hexamethylbenzene analogues [(η(6)-C(6)H(6))(2)Ru(2)(SC(6)H(5))(3)](+) (12) and [(η(6)-C(6)Me(6))(2)Ru(2)(SC(6)H(5))(3)](+) (13). The most active compound [11]Cl was structurally studied by single-crystal X-ray diffraction analysis. The concentrations corresponding to 50 % inhibition of cancer cell growth (IC(50) values) in the A2780 and A2780cisR cell lines of these complexes except for 6 were in the submicromolar range, complex 11 showing an IC(50) value of 0.03 μM in both cell lines. The high in vitro anticancer activity of these complexes may be at least partially due to their catalytic potential for the oxidation of GSH, although there is no clear correlation between the IC(50) values and the turnover frequencies at about 50 % conversion. However, the cytotoxicity is tentatively correlated to the physicochemical properties of the compounds determined by the electronic influence of the substituents X (Hammett constants σ(p)) and the lipophilicity of the thiols p-XC(6)H(4)SH (calculated log P parameters).     

Communication of metal ions in the dinuclear ruthenium complexes containing 4,4′-bipyridine, 1,4-diisocyanobenzene, and pyrazine bridging ligands: Synthesis, characterization and structure determination

Reaction of [Ru(2,2′-bipyridine)(2,2′:6′,2″-terpyridine)Cl]PF₆ (abbreviated to [Ru(bipy)(terpy)Cl]PF₆) with 0.5 equiv of the bidentate ligand L produces the dinuclear complexes [{Ru(bipy)(terpy)}₂(μ-L)](PF₆)₄ (L = 4,4′-bipyridine 1, 1,4-diisocyanobenzene 2 and pyrazine 3) in moderate yields. Treating [Ru(bipy)(terpy)Cl]PF₆ with equal molar of 1,4-diisocyanobenzene affords [Ru(bipy)(terpy)(CNC₆H₄NC)](PF₆)₂ (2a). These new complexes have been characterized by mass, NMR, and UV-Vis spectroscopy, and the structures of 1-3 determined by an X-ray diffraction study. Cyclic voltammetric studies suggest that metal communication between the two ruthenium ions increases from 1 to 2 to 3.     

Synthesis, spectra, dioxygen affinity and antifungal activity of Ru(III) Schiff base complexes

The reaction of ruthenium(III) complexes, [RuX(3)(EPh(3))(3)] (E=As, X=Cl or Br; E=P, X=Cl) and [RuBr(3)(PPh(3))(2)(CH(3)OH)] with bidendate Schiff base ligands derived by condensing salicylaldehyde with methylamine (Hsalmet), cyclohexylamine (Hsalchx), 2-aminopyridine (Hsalampy) have been carried out. The complexes were characterized by analytical and spectral studies (IR, electronic and EPR) and are formulated as [RuX(EPh(3))(LL')(2)] (where LL'=monobasic bidentate Schiff base ligand; E=P or As, X=Cl or Br). An octahedral geometry has been tentatively proposed for the new complexes. Dioxygen affinity of some of the Ru(III) Schiff base complexes was studied by cyclic voltammetry. The representative Schiff bases and their complexes were tested in vitro to evaluate their activity against fungi, namely, Aspergillus flavus (A. flavus) and Fusarium species.