Molybdenum Complexes Bearing the Tris(1-pyrazolyl)methanesulfonate Ligand: Synthesis, Characterization and Electrochemical Behaviour

The tris(1-pyrazolyl)methanesulfonate lithium salt Li(Tpms) [Tpms = SO3C(pz)(3)-] reacts with [Mo(CO)(6)] in NCMe heated at reflux to yield Li[Mo(Tpms)(CO)(3)] (1), which, upon crystallization from thf, forms the coordination polymer [Mo(Tpms)(CO)(2)(mu-CO)Li(thf)(2)](n) (2). Reaction of 1 with I-2, HBF4 or AgBF4 yields [Mo(Tpms)I(CO)(3)] (3), (Mo(Tpms)-H(CO)(3)] (5) or (Mo(Tpms)O-2](2)(mu-O) (7), respectively. The high-oxidation-state dinuclear complexes [{Mo(Tpms)O(mu-O)}(2)] (4) and [{Mo(tpms)OCl)(2)](mu-O) (6) are formed upon exposure to air of solutions of 3 and 5, respectively. Compounds 1-7, which appear to be the first tris(pyrazolyl)methanesulfonate complexes of molybdenum to be reported, were characterized by IR, H-1 and C-13 NMR spectroscopy, ESI-MS, elemental analysis, cyclic voltammetry and, in the cases of Li(Tpms) and compounds 2, 4.2CH(3)CN, 6.6CHCl(3) and 7, by X-ray diffraction analyses. Li(Tpms) forms a 1D polymeric structure (i.e., [Li(tpms)](n)} with Tpms as a tetradentate N2O2 chelating ligand that bridges two Li cations with distorted tetrahedral coordination. Compound 2 is a 1D coordination polymer in which Tpms acts as a bridging tetradentate N3O ligand and each Li(thf)(2)(+) moiety is coordinated by one bridging CO ligand and by the sulfonyl group of a contiguous monomeric unit. In 4, 6 and 7, the Tpms ligand is a tridentate chelator either in the NNO (in 4) or in the NNN (in 6 and 7) fashion. Complexes 1, 3 and 5 exhibit, by cyclic voltammetry, a single-electron oxidation at oxidation potential values that indicate that the Tpms ligand has an electron-donor character weaker than that of cyclopentadienyl.

Protein-ligand docking study: diterpenes from Juniperus brevifolia as anticancer and antimicrobial agentes

REDCAT: Natural Products and related Redox Catalysts: Basic Research and Applications in Medicine and Agriculture, Aveiro, 25-27 Novembro de 2012.

Ligand-Induced structural changes in TEM‑1 probed by molecular dynamics and relative binding free energy calculations

The TEM family of enzymes has had a crucial impact on the pharmaceutical industry due to their important role in antibiotic resistance. Even with the latest technologies in structural biology and genomics, no 3D structure of a TEM- 1/antibiotic complex is known previous to acylation. Therefore, the comprehension of their capability in acylate antibiotics is based on the protein macromolecular structure uncomplexed. In this work, molecular docking, molecular dynamic simulations, and relative free energy calculations were applied in order to get a comprehensive and thorough analysis of TEM-1/ampicillin and TEM-1/amoxicillin complexes. We described the complexes and analyzed the effect of ligand binding on the overall structure. We clearly demonstrate that the key residues involved in the stability of the ligand (hot-spots) vary with the nature of the ligand. Structural effects such as (i) the distances between interfacial residues (Ser70−Oγ and Lys73−Nζ, Lys73−Nζ and Ser130−Oγ, and Ser70−Oγ−Ser130−Oγ), (ii) side chain rotamer variation (Tyr105 and Glu240), and (iii) the presence of conserved waters can be also influenced by ligand binding. This study supports the hypothesis that TEM-1 suffers structural modifications upon ligand binding.

NiII, CuII and ZnII complexes with a sterically hindered scorpionate ligand (TpmsPh) and catalytic application in the diasteroselective nitroaldol (Henry) reaction

The Ni-II and Zn-II complexes [MCl(Tpms(Ph))] (Tpms(Ph) = SO3C(pz(Ph))(3), pz = pyrazolyl; M = Ni 2 or Zn 3) and the Cu-II complex [CuCl(Tpms(Ph))(H2O)] (4) have been prepared by treatment of the lithium salt of the sterically demanding and coordination flexible tris(3-phenyl-1-pyrazolyl)methanesulfonate (Tpms(Ph))(-) (1) with the respective metal chlorides. The (Tpms(Ph))(-) ligand shows the N-3 or N2O coordination modes in 2 and 3 or in 4, respectively. Upon reaction of 2 and 3 with Ag(CF3SO3) in acetonitrile the complexes [M(Tpms(Ph))-(MeCN)](CF3SO3) (M = Ni 5 or Zn 6, respectively) were formed. The compounds were obtained in good yields and characterized by analytic and spectral (IR, H-1 and C-13{H-1} NMR, ESI-MS) data, density functional theory (DFT) methods and {for 4 and [(Bu4N)-Bu-n](Tpms(Ph)) (7), the tatter obtained upon Li+ replacement by [(Bu4N)-Bu-n](+) in Li(Tpms(Ph))} by single crystal X-ray diffraction analysis. The Zn-II and Cu-II complexes (3 and 4, respectively) act as efficient catalyst precursors for the diastereoselective nitroaldol reaction of benzaldehydes and nitroethane to the corresponding beta-nitroalkanols (up to 99% yield, at room temperature) with diastereoselectivity towards the formation of the anti isomer, whereas the Ni-II complex 2 only shows a modest catalytic activity.

The solvation and redox behaviour of mixed ligand COPPER(II) complexes of acetylacetonate and aromatic dimines in ionic liquids

The behavior of two cationic copper complexes of acetylacetonate and 2,2'-bipyridine or 1,10-phenanthroline, [Cu(acac)(bipy)]Cl (1) and [Cu(acac)(phen)]Cl (2), in organic solvents and ionic liquids, was studied by spectroscopic and electrochemical techniques. Both complexes showed solvatochromism in ionic liquids although no correlation with solvent parameters could be obtained. By EPR spectroscopy rhombic spectra with well-resolved superhyperfine structure were obtained in most ionic liquids. The spin Hamiltonian parameters suggest a square pyramidal geometry with coordination of the ionic liquid anion. The redox properties of the complexes were investigated by cyclic voltammetry at a Pt electrode (d = 1 mm) in bmimBF(4) and bmimNTf(2) ionic liquids. Both complexes 1 and 2 are electrochemically reduced in these ionic media at more negative potentials than when using organic solvents. This is in agreement with the EPR characterization, which shows lower A(z) and higher g(z) values for the complexes dissolved in ionic liquids, than in organic solvents, due to higher electron density at the copper center. The anion basicity order obtained by EPR is NTf2-, N(CN)(2)(-), MeSO4- and Me2PO4-, which agrees with previous determinations. (C) 2013 Elsevier B.V. All rights reserved.

Synthesis and structural characterization of new Piano-stool Ruthenium(II) complexes bearing 1-Butylimidazole heteroaromatic ligand

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).

Functional and therapeutical implications of ligand recognition by the scavenger-like lymphocyte receptors CD5 and CD6

Dissertação para obtenção do Grau de Mestre em Genética Molecular e Biomedicina

Ligand K-edge X-ray absorption spectroscopy and DFT calculations on [Fe3S4]0,+ clusters: delocalization, redox, and effect of the protein environment

Ligand K-edge XAS of an [Fe3S4]0 model complex is reported. The pre-edge can be resolved into contributions from the í2Ssulfide, í3Ssulfide, and Sthiolate ligands. The average ligand-metal bond covalencies obtained from these pre-edges are further distributed between Fe3+ and Fe2.5+ components using DFT calculations. The bridging ligand covalency in the [Fe2S2]+ subsite of the [Fe3S4]0 cluster is found to be significantly lower than its value in a reduced [Fe2S2] cluster (38% vs 61%, respectively). This lowered bridging ligand covalency reduces the superexchange coupling parameter J relative to its value in a reduced [Fe2S2]+ site (-146 cm-1 vs -360 cm-1, respectively). This decrease in J, along with estimates of the double exchange parameter B and vibronic coupling parameter ì2/k-, leads to an S ) 2 delocalized ground state in the [Fe3S4]0 cluster. The S K-edge XAS of the protein ferredoxin II (Fd II) from the D. gigas active site shows a decrease in covalency compared to the model complex, in the same oxidation state, which correlates with the number of H-bonding interactions to specific sulfur ligands present in the active site. The changes in ligand-metal bond covalencies upon redox compared with DFT calculations indicate that the redox reaction involves a two-electron change (one-electron ionization plus a spin change of a second electron) with significant electronic relaxation. The presence of the redox inactive Fe3+ center is found to decrease the barrier of the redox process in the [Fe3S4] cluster due to its strong antiferromagnetic coupling with the redox active Fe2S2 subsite.

Kinetic, Structural, and EPR Studies Reveal That Aldehyde Oxidoreductase from Desulfovibrio gigas Does Not Need a Sulfido Ligand for Catalysis and Give Evidence for a Direct Mo-C Interaction in a Biological System

J. Am. Chem. Soc., 2009, 131 (23), pp 7990–7998 DOI: 10.1021/ja809448r

Molecular determinants of ligand specificity in carbohydrate-binding modules: an NMR and X-ray crystallography integrated study

Dissertação para obtenção do Grau de Doutor em Bioquímica – Ramo Bioquímica Estrutural

The FML (Fucose Mannose Ligand) of Leishmania donovani: a new tool in diagnosis, prognosis, transfusional control and vaccination against human kala-azar

The Fucose-Mannose Ligand (FML) of Leishmania donovani is a complex glycoproteic fraction. Its potential use as a tool for diagnosis of human visceral leishmaniasis was tested with human sera from Natal, Rio Grande do Norte, Brazil. The FML-ELISA test, showed 100% sensitivity and 96% specificity, identifying patients with overt kala-azar (p < 0.001, when compared to normal sera), and subjects with subclinical infection. More than 20% apparently healthy subjects with positive reaction to FML developed overt kala-azar during the following 10 months. In the screening of human blood donnors, a prevalence of 5% of sororeactive subjects was detected, attaining 17% in a single day. The GP36 glycoprotein of FHL is specifically reconized by human kala-azar sera. The immunoprotective effect of FML on experimental L. donovanii infection was tested in swiss albino mice. The protection scheemes included three weekly doses of FML, supplemented or not with saponin by the subcutaneous or intraperitoneal routes and challenge with 2x 10(7) amastigotes of Leishmania donovani. An enhancement of 80.0 % in antibody response (p<0.001) and reduction of 85.5 % parasite liver burden (p<0.001) was detected in animals immunized with FML saponin, unrespectivety of the immunization route.

Electron Transfer and Ligand Binding Properties of Cytochromes

Dissertation presented to obtain the Ph.D degree in Biochemistry

Copper toxicity for Scinax ruber and Rhinella granulosa (Amphibia: Anura) of the Amazon: Potential of Biotic Ligand Model to predict toxicity in urban streams

In the last years many populations of anurans have declined and extinctions have been recorded. They were related to environmental pollution, changes of land use and emerging diseases. The main objective of this study was to determine copper sensitivity of the anuran of the Amazon Rhinella granulosa and Scinax ruber tadpoles at stage 25 and Scinax ruber eggs exposed for 96 h to copper concentrations ranging from 15 µg Cu L-1 to 94 µg Cu L-1. LC50 at 96 h of Rhinella granulosa Gosner 25, Scinax ruber Gosner 25 and Scinax ruber eggs in black water of the Amazon were 23.48, 36.37 and 50.02 µg Cu L-1, respectively. The Biotic Ligand Model was used to predict the LC50 values for these species and it can be considered a promising tool for these tropical species and water conditions. Copper toxicity depends on water physical-chemical composition and on the larval stage of the tadpoles. The Gosner stage 19-21 (related to the appearance of external gills) is the most vulnerable and the egg stage is the most resistant. In case of contamination by copper, the natural streams must have special attention, since copper is more bioavailable.

Ingeniería de glicanos: diseño de inmunógenos y ligandos de lectinas. Glycan engineering: design of immunogens and ligand of lectins.

La ingeniería de glicanos es un área de investigación emergente, la que posee múltiples aplicaciones en medicina. Mediante esta herramienta se intentará reducir la flexibilidad de las uniones glicosídicas de antígenos tumorales, como la del antígeno T (Galbeta3GalNAcalfa-Ser/Thr). Aquí se realizarán las menores alteraciones posibles en la topología de glicanos que generen la mejor respuesta inmune hacia el antígeno de interés. Por otra parte, se buscará ligandos de alta afinidad que interaccionen con lectinas involucradas en diseminación de metástasis. Mediante ensayos teóricos de Docking se tratará de hallar modificaciones topológicas de glicanos que potencialmente tengan propiedades anti-adhesivas para células tumorales. Este proyecto constará de tres etapas: una teórica, utilizando programas de cálculos para ensayos de Docking y mínimos energéticos de glicanos. Otra de síntesis, generando los glicoconjugados sugeridos en la etapa anterior. En la última, se verificará si estos glicanos rediseñados adquirieron las propiedades biológicas deseadas. Así se determinará si generan una respuesta inmune que reconozca antígenos y células tumorales. También, se analizarán las propiedades anti-adhesivas de los glicanos utilizando diferentes modelos experimentales. Finalmente, se determinará si los inmunógenos producidos y/o glicoconjugados rediseñados poseen efecto en el desarrollo tumoral y sobrevida animal.