In this work, we investigated the anticancer activity of several novel silver(I) 2,2'-bipyridine complexes containing either triphenylphosphane (PPh3) or 1,2-bis(diphenylphosphino)ethane (dppe) ligands. All compounds were characterized by diverse analytical methods including ESI-MS spectrometry; NMR, UV-vis, and FTIR spectroscopies; and elemental analysis. Moreover, several compounds were also studied by X-ray single-crystal diffraction. Subsequently, the compounds were investigated for their anticancer activity against drug-resistant and -sensitive cancer cells. Noteworthily, neither carboplatin and oxaliplatin resistance nor p53 deletion impacted on their anticancer efficacy. MES-OV cells displayed exceptional hypersensitivity to the dppe-containing drugs. This effect was not based on thioredoxin reductase inhibition, enhanced drug uptake, or apoptosis induction. In contrast, dppe silver drugs induced paraptosis, a novel recently described form of programmed cell death. Together with the good tumor specificity of this compound's class, this work suggests that dppe-containing silver complexes could be interesting drug candidates for the treatment of resistant ovarian cancer.

Four new Cu(I) complexes of the general formula [Cu(PP)(LL)][BF4], in which PP is a phosphane ligand (triphenylphosphane or 1,2‐bis(diphenylphosphano)ethane (dppe)) and LL is a bioactive thiosemicarbazone ligand (4‐(methyl)‐1‐(5‐nitrofurfurylidene)thiosemicarbazone) or 4‐(ethyl)‐1‐(5‐nitrofurfurylidene)thiosemicarbazone) were synthesized and fully characterized by classical analytical and spectroscopic methods. The anti‐trypanosome and anticancer activities were investigated in vitro on Trypanosoma cruzi and in two human cancer cell lines (ovarian OVCAR3 and prostate PC3). To test the selectivity toward parasites and cancer cells, the cytotoxicity on normal monkey kidney VERO and human dermal fibroblasts HDF cells was also evaluated. The new heteroleptic complexes were more cytotoxic on T. cruzi and chemoresistant prostate PC3 cells than the benchmark drugs nifurtimox and cisplatin. The compounds also showed a high level of cellular internalization by the OVCAR3 cells and, in particular, those containing the dppe phosphane showed activation of the cell death mechanism via apoptosis. On the other hand, the production of reactive oxygen species induced by these complexes was not evident.

Synthesis of a new family of Cu(i)–phosphane complexes with N,O-heteroaromatic ligands leads to the complexes showing impressive cytotoxicity against LNCap human prostate cancer cells allied to high selectivity than against RWPE non-tumoral prostate cells.

First heterobimetallic Cu(i)–dppf complexes with bidentate heteroaromatic ligands designed for anticancer applications.

Synthesis of new phosphane–Cu(i) complexes with bidentate ligands displaying cytotoxic and cytostatic effects that make them attractive as anticancer agents.

A new family of copper(I) complexes of general formula [Cu(dppe)(NN)]+ have been synthesized and fully characterized, with dppe=1.2-bis(diphenylphosphino)ethane and NN representing several bidentate heteroaromatic ligands: 2,2'-bipy=2.2'-bipyridine (1), Me2bpy=4.4'-dimethyl-2,2'-bipyridine (2), dpytz=3-(2-pyridyl)-5,6-diphenyl-1,2,4-triazine (3), dpp=2.3-bis(2-pyridyl)pyrazine (4), and the metallaligand [Ru(η5-C5H5)(PPh3)(dpp)]+ (5), yielding the bimetallic copper(I)-ruthenium(II) complex [Cu(dppe)(μ-dpp)Ru(η5-C5H5)(PPh3)]2+ (6). The single crystal structures of complexes (2) and (4) were determined by X-ray diffraction studies. All the complexes exhibit high cytotoxicity against the human cancer cells A2780 and MCF7 with IC50 values far lower than those found for the antitumor drug cisplatin in the same cell lines and even surpassing cisplatin resistance in the A2780cisR cells. They display IC50 values on the human embryonic kidney HEK293 non-tumoral cells of the same order of magnitude as those found for the tumoral cells. In the ovarian cells the compounds induce rapid production of reactive oxygen species (ROS) probably through mitochondrial pathways. According to the results reported here, these compounds can be considered as prospective antitumoral agents that deserve further evaluation.

The influence of temperature (20-40 °C) on the acetaminophen adsorption onto activated carbons with different textures was studied. Different temperature dependences, not explained by kinetic effects, were observed for carbons with different micropore size distribution patterns: adsorption capacity increased for pine gasification residues (Pi-fa) derived carbons and decreased for sisal based materials. No significant variation was seen for carbon CP. The species identified by (1)H NMR spectroscopy on the back-extraction solution proved that during the adsorption process exist the conditions required to promote the formation of acetaminophen oligomers which have constrained access to the narrow microporosity. The rotation energy of the dihedral angle between monomers (estimated by electronic DFT methods) showed that conformations in the planar form are less stable than the non-planar conformation (energy barrier of 70 and 23 kJ mol(-1)), but have critical dimensions similar to the monomer and can access most of the micropore volume. The enthalpy change of the overall process showed that the energy gain of the system (endothermic) for Pi-fa samples (≈40 kJ mol(-1)) was enough to allow a change in the dimer, or even a larger oligomer, conformation to the planar form. This will permit adsorption in the narrow micropores, thus explaining the uptake increase with temperature. Non-continuous micropore size distributions centered at pore widths close to the critical dimensions of the planar form seem to be crucial for a positive evolution of the adsorption capacity with temperature.

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The purpose of this work was to synthesize and characterize the thiatetraaza macrocycle 1-thia-4,7,10,13-tetraazacyclopentadecane ([15]aneN4S). Its acid-base behaviour was studied by potentiometry at 25 °C and ionic strength 0.10 M in KNO3. The protonation sequence of this ligand was investigated by 1H-NMR titration that also allowed the determination of protonation constants in D2O. Binding studies of [15]aneN4S with Mn2+, Fe2+, Co2+, Ni2+, Cu2+, Zn2+, Cd2+, Hg2+ and Pb2+ metal ions were further performed under the same experimental conditions. The results demonstrated that this compound has a higher selectivity and thermodynamic stability for Hg2+ and Cu2+, followed by Ni2+. The UV-visible-near IR spectroscopies and magnetic moment data for the Co(II) and Ni(II) complexes indicated a tetragonal distorted coordination geometry for both metal centres. The value of magnetic moment and the X-band EPR spectra of the Cu(II) complex are consistent with a distorted square pyramidal geometry.

New ferrocenyl derivatives with the general formula FcC(O)L [Fc = (eta(5)-C5H5)Fe(eta(5)-C5H4)], where L is an aminoquinoline or hydroxyaminoquinoline, have been synthesized for evaluation of their leishmanicidal properties. The compounds were designed with ferrocene coupled to the quinolines by an amide or ester bridge. Ferrocenyl component is intended to act as quinoline carrier and ROS producer after in vivo oxidation to Fe(III), while decreasing normal cell cytotoxicity of coupled quinolines. The bridge was chosen based on its known ability to undergo hydrolysis by the protease/esterase rich media in phagolysosomes, the target of the intracellular form of leishmania parasites.The new compounds include N-(quinolin-3-yl)ferrocenamide (4), N-(quinolin-5-yl)ferrocenamide (5), N-(quinolin-6-yl)ferrocenamide (6), N-(2-methyl-quinolin-4-yl)ferrocenamide (7), N-(2-methylquinolin-6yl)ferrocenamide (8), N-(6-methoxy-quinolin-8-yl)ferrocenamide (9), 2-amino-quinolin-8-yl ferrocenoate (10) and 2-amino-quinolin-4-yl ferrocenoate (11). They were characterized by NMR, cyclic voltammetry, mass spectrometry, UV/vis, FT-IR and elemental analysis, which confirmed all the proposed molecular structures. Compounds 7 and 8 were also structurally characterized by single crystal X-ray diffraction. In 7, the 4-amino-2-methylquinoline moiety is perpendicular to the substituted cyclopentadienyl ring (Cp), while in 8 the 6-amino-2-methylquinoline component is coplanar to the substituted Cp.The new compounds (4-11), same as four other previously published (1-ferrocenoyl-1H-(2-aminobenzimidazole) (1), 1-ferrocenoyl-1H-benzimidazole (2), 1-ferrocenoyl-1H-imidazole (3) and N-(pyridin-4-yl)ferrocenamide (12)), were evaluated in vitro in cultures of a Leishmania infantum strain, isolated from a human visceral leishmaniasis case, to establish their leishmanicidal activity. The toxicity against the human caucasian histiocytic lymphoma U-937 cell line was analyzed for the same set of compounds. All of them show activity against promastigote forms of L. infantum parasites at relatively high concentration (64-269 mu M). Among the complexes that showed a better ratio between the toxic and the therapeutic dose, 3, 9 and 12 were selected for further studies in infected macrophages. Such compounds showed a very significant increase in their activity (17-23 times) giving very similar IC50 values (5.2-5.7 mu M). All three compounds gave significantly better therapeutic indexes (88.5, 12; 56.4, 3; 16.6, 9) than the control miltefosine (6.1).(2) (C) 2013 Elsevier B.V. All rights reserved.

A silsesquioxane cage polymer functionalized with eight chloropropyl arms (1, T-8-PrCl) reacted with 2,2'-dipyridiylamine (DPA) to afford a new derivative with eight pendant linear chains (2, T-8-Pr-DPA). Further reaction with [Mo(eta(3)-C3H5)Br(CO)(2)(NCMe)(2)] afforded another derivative containing three molybdenum units (3, T-8-Pr-DPA-Mo), after substitution of the two nitrite ligands in each complex. These are the first silsesquioxane species containing DPA and the Mo(eta(3)-C3H5)Br(CO)(2) fragment. The three materials were characterized by H-1, C-13, Si-29, and Mo-95 NMR, FTIR, XRD, and elemental analysis, and T-8-PrCl (1) was also structurally characterized by single-crystal X-ray diffraction. It was identified as a low-temperature polymorph of this material. Elemental analysis indicated that all Cl atoms in the parent material T-8-PrCl (1) were substituted by the deprotonated DPA group in T-8-Pr-DPA (2). However, only three [Mo(eta(3)-C3H5)Br(CO)(2)(DPA)] units were detected in T-8-Pr-DPA-Mo (3). A comprehensive NMR study, complemented with DFT calculations, was carried out in order to detect the effect of Mo coordination on the cage silicon and on the protons and carbons of the propyl chain, but no significant effects were observed. Both H-1 and Si-29 chemical shifts vary upon introducing DPA but remain the same after reaction with the Mo(II) precursor. The Mo-95 NMR data reveal that the metal is not sensitive to the cage. The catalytic activity of 3 was tested as a precursor in the epoxidation of cyclooctene and styrene in the presence of TBHP. Despite the high selectivity toward the epoxides, the conversion and turnover frequencies were low, reflecting the behavior of the [Mo(eta(3)-C3H5)Br(CO),(DPA)] complex.

New cationic ruthenium(II) complexes with the formula [Ru(eta(5)-C5H5)(LL)(1-BuIm)] [Z], with (LL) = 2PPh(3) or DPPE, and Z = CF3SO3-, PF6-, BPh4-, have been synthesized and fully characterized. Spectroscopic and electrochemical studies revealed that the electronic properties of the coordinated 1-butylimidazole were clearly influenced by the nature of the phosphane coligands (LL) and also by the different counter ions. The solid state structures of the six complexes determined by X-ray crystallographic studies, confirmed the expected distorted three-legged piano stool structure. However the geometry of the 1-butylimidazole ligand was found considerably different in all six compounds, being governed by the stereochemistry of the mono and bidentate coligands (PPh3 or DPPE). (C) 2012 Elsevier B.V. All rights reserved.

Molybdenum(II) complexes [MOX(CO)(2)(eta(3)-allyl)(CH3CN)(2)] (X = Cl or Br) were encapsulated in an aluminium-pillared natural clay or a porous clay heterostructure and allowed to react with bidentate diimine ligands. All the materials obtained were characterised by several solid-state techniques. Powder XRD, and Al-27 and Si-29 MAS NMR were used to investigate the integrity of the pillared clay during the modification treatments. C-13 CP MAS NMR, FTIR, elemental analyses and low-temperature nitrogen adsorption showed that the immobilisation of the precursor complexes was successful as well as the in situ ligand-substitution reaction. The new complex [MoBr(CO)(2)(eta(3)-allyl)(2-aminodipyridyl)] was characterised by single-crystal X-ray diffraction and spectroscopic techniques, and NMR studies were used to investigate its fluxional behaviour in solution. The prepared materials are active for the oxidation of cis-cyclooctene using tert-butyl hydroperoxide as oxidant, though the activity of the isolated complexes is higher. ((c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008).

The reaction of [MoCp2(SR)2] (R=CH3, C2H5, n-C14H29 or C6H5) with InCl3 in ethanol affords new compounds which, after treatment with NH4PF6, were fully characterized as the hexafluorophosphate salts [InMoCp2(μ-SR)23] [PF6]3.

New bridged fulvalene (Fv = μ-η5 : η5-C10)H8) binuclear molybdenum(III) and tungsten(III) compounds were obtained from the reaction of [M(η5-C5H5)2(SC6H5)2] (M = Mo or W) with dirhenium decacarbonyl. The complex [Mo2Fv(μ-SC6H5)Cp2][Re2(μ-SPh)3(CP)6] was characterized by single crystal X-ray diffraction. The cation [Mo2Fv(μ-SC6H5)Cp2]+ showed a relatively rigid [Mo2FvCp2] unit with an Mo-S-Mo angle of 83.88(7)°, M-S distances 2.442(2) and 2.450(2) Å and a Mo⋯Mo distance of 3.256(1) Å. In the [Re2(μ-SPh)3(CO)6]− anion, each metal atom has an octahedral environment (three carbonyl and three thiolate groups) with the two octahedra sharing the face containing the sulphur donor atoms (Re-S-Re angles from 86.63(8) to 86.83(8)°). The Re⋯Re distance of 3.457(1) Å is long. Extended Hückel molecular orbital calculations were done in order to understand the nature of the metal-metal interaction in the cation and some related complexes. Although the Mo⋯Mo distance is relatively long, there is a strong interaction between the two d3 metal atoms, assigned to a μ bond, which leads to diamagnetic behaviour (the anion with two d6 ReI centres is also diamagnetic).