Ruthenium p-Cymene Complexes Incorporating Substituted Pyridine-Quinoline-Based Ligands: Synthesis, Characterization, and Cytotoxic Properties.

Organometallic complexes of the formula [Ru(N^N)(p-cymene)Cl][X] (N^N = bidentate polypyridyl ligands, p-cymene = 1-methyl-4-(1-methylethyl)-benzene, X = counter anion), are currently studied as possible candidates for the potential treatment of cancer. Searching for new organometallic compounds with good to moderate cytotoxic activities, a series of mononuclear water-soluble ruthenium(II)-arene complexes incorporating substituted pyridine-quinoline ligands, with pending -CH2OH, -CO2H and -CO2Me groups in the 4-position of quinoline ring, were synthesized, for the first time, to study their possible effect to modulate the activity of the ruthenium p-cymene complexes. These include the [Ru(η6-p-cymene)(pqhyme)Cl][X] (X = Cl- (1-Cl), PF6- (1-PF6), pqhyme = 4-hydroxymethyl-2-(pyridin-2-yl)quinoline), [Ru(η6-p-cymene)(pqca)Cl][Cl] ((2-Cl), pqca = 4-carboxy-2-(pyridin-2-yl)quinoline), and [Ru(η6-p-cymene)(pqcame)Cl][X] (X = Cl- (3-Cl), PF6- (3-PF6), pqcame = 4-carboxymethyl-2-(pyridin-2-yl)quinoline) complexes, respectively. Identification of the complexes was based on multinuclear NMR and ATR-IR spectroscopic methods, elemental analysis, conductivity measurements, UV-Vis spectroscopic, and ESI-HRMS techniques. The solid-state structures of 1-PF6 and 3-PF6 have been elucidated by single-crystal X-ray diffraction revealing a three-legged piano stool geometry. This is the first time that the in vitro cytotoxic activities of these complexes are studied. These were conducted in HEK293T (human embryonic kidney cells) and HeLa cells (cervical cancer cells) via the MTT assay. The results show poor in vitro anticancer activities for the HeLa cancer cell lines and 3-Cl proved to be the most potent (IC50 > 80 µΜ). In both cell lines, the cytotoxicity of the ligand precursor pqhyme is significantly higher than that of cisplatin.

First-Row Transition Metal Complexes Incorporating the 2-(2'-pyridyl)quinoxaline Ligand (pqx), as Potent Inflammatory Mediators: Cytotoxic Properties and Biological Activities against the Platelet-Activating Factor (PAF) and Thrombin.

Inflammatory mediators constitute a recently coined term in the field of metal-based complexes with antiplatelet activities. Our strategy targets Platelet-Activating Factor (PAF) and its receptor, which is the most potent lipid mediator of inflammation. Thus, the antiplatelet (anti-PAF) potency of any substance could be exerted by inhibiting the PAF-induced aggregation in washed rabbit platelets (WRPs), which internationally is a well-accepted methodology. Herein, a series of mononuclear (mer-[Cr(pqx)Cl3(H2O]) (1), [Co(pqx)Cl2(DMF)] (2) (DMF = N,N'-dimethyl formamide), [Cu(pqx)Cl2(DMSO)] (3) (DMSO = dimethyl sulfoxide), [Zn(pqx)Cl2] (4)) and dinuclear complexes ([Mn(pqx)(H2O)2Cl2]2 (5), [Fe(pqx)Cl2]2 (6) and [Ni(pqx)Cl2]2 (7)) incorporating the 2-(2'-pyridyl)quinoxaline ligand (pqx), were biologically evaluated as inhibitors of the PAF- and thrombin-induced aggregation in washed rabbit platelets (WRPs). The molecular structure of the five-co-ordinate analog (3) has been elucidated by single-crystal X-ray diffraction revealing a trigonal bipyramidal geometry. All complexes are potent inhibitors of the PAF-induced aggregation in WRPs in the micromolar range. Complex (6) displayed a remarkable in vitro dual inhibition against PAF and thrombin, with IC50 values of 1.79 µM and 0.46 µM, respectively. Within the series, complex (5) was less effective (IC50 = 39 µM) while complex (1) was almost 12-fold more potent against PAF, as opposed to thrombin-induced aggregation. The biological behavior of complexes 1, 6 and 7 on PAF's basic metabolic enzymatic pathways reveals that they affect key biosynthetic and catabolic enzymes of PAF underlying the anti-inflammatory properties of the relevant complexes. The in vitro cytotoxic activities of all complexes in HEK293T (human embryonic kidney cells) and HeLa cells (cervical cancer cells) are described via the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The results reveal that complex 3 is the most potent within the series.

Tin(II) and Tin(IV) Complexes Incorporating the Oxygen Tripodal Ligands [(η5-C5R5)Co{P(OEt)2O}3]-, (R = H, Me; Et = -C2H5) as Potent Inflammatory Mediator Inhibitors: Cytotoxic Properties and Biological Activities against the Platelet-Activating Factor (PAF) and Thrombin.

Metal complexes displaying antiplatelet properties is a promising research area. In our methodology, Platelet-Activating Factor (PAF), the most potent lipid pro-inflammatory mediator, serves as a biological probe. The antiplatelet activity is exerted by the inhibition of the PAF-induced aggregation in washed rabbit platelets (WRPs) and in rabbit plasma rich in platelets (rPRPs). Herein, the synthesis and biological investigation of a series of organometallic tin(II) and tin(IV) complexes, featuring the oxygen tripodal Kläui ligands [(η5-C5R5)Co{P(OEt)2O}3]-, {R = H, (LOEt-); Me (L*OEt-)}, are reported. Reaction of NaLOEt (1a) and NaL*OEt (1b) with SnCl2, yielded the rare four-coordinate LOEtSnCl (2a) and L*OEtSnCl (2b) complexes. Accordingly, LOEtSnPh3 (3a) and L*OEtSnPh3 (3b) were prepared, starting from Ph3SnCl. Characterization includes spectroscopy and X-ray diffraction studies for 2a, 2b and 3b. The antiplatelet activity of the lead complexes 2b and 3a (IC50 = 0.5 µΜ) is superior compared to that of 1a and 1b, while both complexes display a pronounced inhibitory activity against thrombin (IC50 = 1.8 µM and 0.6 µM). The in vitro cytotoxic activities of 3a and 2b on human Jurkat T lymphoblastic tumor cell line is higher than that of cisplatin.

Sterically demanding pyridine-quinoline anchoring ligands as building blocks for copper(I)-based dye-sensitized solar cell (DSSC) complexes.

The Pfitzinger condensation reaction was employed to synthesise N^N sterically demanding ligands bearing carboxylic acid anchoring groups, namely 2,2'-pyridyl-quinoline-4-carboxylic acid (pqca), 6'-methyl-2,2'-pyridyl-quinoline-4-carboxylic acid (6'-Mepqca), 8-methyl-2,2'-pyridyl-quinoline-4-carboxylic acid (8-Mepqca) and 8,6'-dimethyl-2,2'-pyridyl-quinoline-4-carboxylic acid (8,6'-Me2pqca). Preparation of the methyl ester analogues 6'-Mepqcame, 8-Mepqcame and 8,6'-Me2pqcame is also described. All ligands were fully characterised including the X-ray structures of pqca, 6'-Mepqca and 8-Mepqca. We also describe the synthesis and characterisation of seven homoleptic copper(I) complexes of the formula [Cu(N^N)2][PF6] (N^N = pqca (1), 6'-Mepqca (2), 8-Mepqca (3), 8,6'-Me2pqca (4), 6'-Mepqcame (6), 8-Mepqcame (7) and 8,6'-Me2pqcame (8)). Characterisation of the copper(I) complexes includes FT-IR, elemental analyses, multinuclear NMR spectroscopy, UV-vis spectroscopy, cyclic voltammetry, and a single-crystal X-ray diffraction study. The molecular structures of 1·DMSO, 2{2·Me2CO·0.5H2O}, 4, 6·CHCl3·0.13H2O, 2{7·C5H12}·CHCl3 and 8 have been determined, revealing that these complexes adopt a distorted tetrahedral geometry. These are the first crystallographically characterised examples of copper(I)-based coordination compounds incorporating the above mentioned N^N pyridyl-quinoline ligands. In solution, the new complexes are purple to red colored, while 2 displayed excellent stability in acetone at ambient temperature over a month. The absorption spectra of 1-8 display a main broad MLCT band with values of λmax at ∼530 nm and ε values ranging from 1800 to approximately 10 000 dm3 mol-1 cm-1. The photovoltaic performance of the prepared compounds was evaluated on mesoporous nanocrystalline TiO2 dye-sensitized solar cells (DSSCs), and compared with that of the [Cu(dmdcbpy)2][PF6] dye (dmdcbpy = 6,6'-dimethyl-2,2'-bipyridine-4,4'-dicarboxylic acid) (5), that has been used as standard, under the same experimental conditions. From a combination of electrochemical and absorption spectroscopy experiments, the MLCT energy levels of 2 are appropriate for electron injection onto the titania conduction band. Upon optimisation of the semiconductor's architecture, 2 proved to be the most efficient dye, reaching a conversion efficiency of η = 1.20%, which is slightly higher than that of 5 (η = 1.05%), mainly attributed to higher Voc values.

Surfactant Effects on the Synthesis of Redox Bifunctional V2O5 Photocatalysts.

Novel V2O5 bifunctional photocatalysts were prepared following a wet chemical process with the addition of anionic or non-ionic surfactants into the precursor solution and further heating under reflux. Detailed characterization and investigation of the relevant light-matter interactions proved that surfactants addition had a strong impact on the morphology, while also affecting the crystallinity, the optoelectronic properties, and the surface chemistry of the novel photocatalysts. The most efficient photocatalyst (T80) was based on tween 80, a surface-active agent employed for the first time in the synthesis of vanadium oxide materials. T80 presented crystalline nature without structural defects, which are usually centers of e- - h+ recombination. This material also exhibited small crystal size, high porosity, and short migration paths for the charge carriers, enabling their effective separation during photocatalysis. Under UV light illumination, T80 was capable to reduce hexavalent chromium to trivalent up to 70% and showed high yields in degrading methylene blue azo-dye and tetracycline antibiotic water pollutants. This remarkably high bifunctional performance defines T80 as a promising and capable photocatalytic material for both advanced oxidation and reduction processes (AOPs-ARPs).

A Review on Platelet Activating Factor Inhibitors: Could a New Class of Potent Metal-Based Anti-Inflammatory Drugs Induce Anticancer Properties?

In this minireview, we refer to recent results as far as the Platelet Activating Factor (PAF) inhibitors are concerned. At first, results of organic compounds (natural and synthetic ones and specific and nonspecific) as inhibitors of PAF are reported. Emphasis is given on recent results about a new class of the so-called metal-based inhibitors of PAF. A small library of 30 metal complexes has been thus created; their anti-inflammatory activity has been further evaluated owing to their inhibitory effect against PAF in washed rabbit platelets (WRPs). In addition, emphasis has also been placed on the identification of preliminary structure-activity relationships for the different classes of metal-based inhibitors.

Inorganic tin compounds do not induce micronuclei in human lymphocytes in the absence of metabolic activation.

The genotoxic evaluation (in vitro analysis) of a series of eight inorganic tin(II) and tin(IV) compounds [tin(II) acetate, tin(II) chloride, tin(II) ethylhexanoate, tin(II) oxalate, tin(II) oxide, tin(IV) acetate, tin(IV) chloride and tin(IV) oxide], for the detection of micronuclei in human blood lymphocytes, was performed in the absence of metabolic activation by the cytokinesis-block micronucleus assay. Human lymphocytes were treated for over one cell cycle (31 hours), with concentrations ranging from 1 to 75 µM (1, 5, 10, 20, 50 and 75 µM), of tin(II) and tin(IV) salts dissolved in dimethyl sulfoxide. The above-listed concentrations cover the values that have been detected in humans with no occupational exposure to tin compounds. The experimental results show the absence of genotoxicity for all inorganic compounds tested in the specific concentrations and experimental conditions. Cytotoxic effects of tin(II) and tin(IV) compounds were evaluated by the determination of cytokinesis block proliferation index and cytotoxicity percentage. Our observations on the cytotoxicity pattern of the tested tin(II) and tin(IV) compounds indicate that they are cytotoxic in several tested concentrations to human lymphocytes treated in vitro. The observed differences in cytotoxicity of each tested compound might reflect differences in their chemical structure.

Synthesis, biochemical evaluation and molecular modeling studies of novel rhodium complexes with nanomolar activity against Platelet Activating Factor.

Two square planar Rh(I) organometallic complexes namely [Rh(L(1))(cod)]Cl (cod = cycloocta-1,5-diene, L(1)=2,2'-pyridylquinoxaline (1-Cl), [Rh(L1)(cod)](NO3) (1-NO(3)) and a series of novel octahedral rhodium(III) complexes of the general formulae mer-[Rh(L(1))Cl(3)(MeOH)] (2) and cis-[Rh(L(2))(2)Cl(2)]Cl (L(2)=4 carboxy 2 (2' pyridyl)quinoline (3), L(3)=2,2' bipyridine 4,4' dicarboxylic acid (4) were synthesized and characterized spectroscopically. All the synthesized compounds including the previously prepared cis-[Rh(L(1))(2)Cl(2)]Cl complex (5) were biologically evaluated as potential inhibitors of the Platelet Activation Factor (PAF) and thrombin induced aggregation. In particular compounds 1-Cl and 1-NO(3) were found to be strong inhibitors of PAF with IC(50) values in the range of 16 nM and 15 nM rendering them good candidates for further investigation. Their potency is comparable to that of the widely used PAF receptor antagonists WEB2170, BN52021, and Rupatadine (IC(50) of 20, 30 and 260 nM respectively). Molecular docking calculations suggest that 1-Cl, 1-NO3 and 2 can be accommodated within the ligand-binding site of PAF receptor and block the activity of PAF. On the other hand, the octahedral rhodium(III) complexes 3-5 that cannot fit the ligand-binding domain, could potentially exhibit their activity at the extracellular domain of the receptor.

Influence of pyridine ligand nature and the corresponding ruthenium(II) dye molecular structure on the performance of dye-sensitized solar cells.

cis-[Ru(bpy)(2)(L(n))]Cl(2) (n = 1, L(1) = 4-carboxy-2-(2'-pyridyl)quinoline (); n = 2, L(2) = 2,2'-pyridine-4,4'-dicarboxylic acid ()); and cis-[Ru(bpy)(2)(L')(2))]Cl(2) (L' = 4-pyridinecarboxylic acid ()) complexes, with surface anchoring groups, are prepared from the reaction of cis-[Ru(bpy)(2)Cl(2)] () with the appropriate ligand (L(1), L(2), L'). Ion exchange in aqueous solution with NH(4)PF(6) gives the corresponding bis(hexafluorophosphate) derivatives cis-[Ru(bpy)(2)(L(1))](PF(6))(2) (), cis-[Ru(bpy)(2)(L(2))](PF(6))(2) () and cis-[Ru(bpy)(2)(L')(2)](PF(6))(2) (), respectively. The photo-electrochemical properties of the dyes () are investigated and the efficiency of the corresponding dye sensitized solar cells is compared to a N719 sensitized device, under similar fabrication and testing conditions.

Transition-Metal Derivatives of a Functionalized Cyclopentadienyl Ligand. 15. Synthesis and Structures of Amino Cyclopentadienyl Derivatives of Rhodium(I) and Rhodium(III) Including Water-Soluble Compounds.

The synthesis of monometallic rhodium(III) and rhodium(I) derivatives of dialkylamino-functionalized cyclopentadienyl using the corresponding cyclopentadiene as starting material is facilitated by the presence of the basic amino group. This procedure affords the chloro salts of the substituted rhodicinium cation [(eta(5)-C(5)H(4)(CH(2))(2)NMe(2)H)(2)Rh(III)](3+) ([1][Cl](3)) from the reaction of the [2-(dimethylamino)ethyl]cyclopentadiene with Na(3)Rh(III)Cl(6). 12H(2)O. Similarly the cationic half-sandwich complexes [(eta(5)-C(5)H(4)(CH(2))(n)()NMe(2)H)Rh(I)(cod)](+) (n = 2, [2][Cl], n = 3, [5][Cl]) are obtained from the reaction of the corresponding dialkylamino cyclopentadiene with [RhCl(cod)](2). These types of cationic complexes, 1, 2, and 5, bear pendant ammonium groups. The most classical procedure, starting from the lithium or more efficiently from the sodium cyclopentadienide salt, was used to synthesize neutral complexes [(eta(5)-C(5)H(4)(CH(2))(n)()NMe(2))Rh(I)(cod)] (n = 2, 3; n = 3, 4). The structure of the chloride bis(hexafluorophosphate) salt, [(eta(5)-C(5)H(4)(CH(2))(2)NMe(2)H)(2)Rh(III)](3+)(Cl(-))(PF(6)(-))(2), ([1][Cl][PF(6)](2)) was solved in the triclinic space group P&onemacr; with one molecule in the unit cell, the dimensions of which are a = 6.617(2) Å, b= 7.436(2) Å, c = 13.965(3) Å, alpha = 76.39(2) degrees, beta = 82.31(3) degrees, gamma = 87.26(2) degrees, and V = 661.8(3) Å(3). The noncentrosymmetric character of this solid is attributed to the chloride ion. The tetrafluoroborate salt [(eta(5)-C(5)H(4)(CH(2))(2)NMe(2)H)Rh(I)(cod)](+)(BF(4)(-)) ([2][BF(4)]) crystallizes in the tetragonal space group P4(2)/n with eight molecules in the unit cell, the dimensions of which are a= 21.183(2) Å, b = 21.179(3) Å, c= 8.324(2) Å, and V = 3734(1) Å(3). Least squares refinement leads to values for the conventional R index of [1][Cl][PF(6)](2) (0.0484 for 2191 reflections used) and of [2][BF(4)] (0.0525 for 1083 reflections used); in both cases I > 3sigma(I). As expected, compounds like [2][Cl](3,) [1][Cl][PF(6)](2), [2][Cl], [2][BF(4)], [5][Cl], and [5][BF(4)] are soluble in water.