Synthesis and stereochemistry of some bicyclic gamma-lactones from parasitic wasps (Hymenoptera : Braconidae). Utility of hydrolytic kinetic resolution of epoxides and palladium(II)-catalyzed hydroxycyclization-carbonylation-lactonization of ene-diols

A palladium(II)-catalyzed hydroxycyclization-carbonylation-lactonization sequence with appropriate pent-4-ene-1,3-diols provides efficient access to the bicyclic gamma -lactones, 5-n-butyl- and 5-n-hexyltetrahydrofuro-[3,2-b]furan-2(3H)-ones (3) and (4), respectively, in both racemic and enantiomeric forms. Some of the substrate pent-4-ene-1,3-diols of high enantiomeric excess (ee) have been derived from racemic terminal epoxides by hydrolytic kinetic resolution (HKR) using cobalt (III)-salen complexes. (9Z,12R)-(+)-Ricinoleic acid also serves as a chiral pool source of other pent-4-ene-1,3-diols. These syntheses and enantioselective gas chromatography confirm the structures and absolute stereochemistry of the lactones in some species of parasitic wasps (Hymenoptera: Braconidae). The highly abundant 5-n-hexyltetrahydrofuro-[3,2-b]furan-2(3H)-one (4) in Diachasmimorpha kraussii and D. longicaudata is of high ee (> 99%) with (3aR,5R,6aR) stereochemistry.

Caveolin interacts with the angiotensin II type 1 receptor during exocytic transport but not at the plasma membrane

The mechanisms involved in angiotensin II type 1 receptor (AT(1)-R) trafficking and membrane localization are largely unknown. In this study, we examined the role of caveolin in these processes. Electron microscopy of plasma membrane sheets shows that the AT(1)-R is not concentrated in caveolae but is clustered in cholesterol-independent microdomains; upon activation, it partially redistributes to lipid rafts. Despite the lack of AT(1)-R in caveolae, AT(1)-R. caveolin complexes are readily detectable in cells co-expressing both proteins. This interaction requires an intact caveolin scaffolding domain because mutant caveolins that lack a functional caveolin scaffolding domain do not interact with AT(1)-R. Expression of an N-terminally truncated caveolin-3, CavDGV, that localizes to lipid bodies, or a point mutant, Cav3-P104L, that accumulates in the Golgi mislocalizes AT(1)-R to lipid bodies and Golgi, respectively. Mislocalization results in aberrant maturation and surface expression of AT(1)-R, effects that are not reversed by supplementing cells with cholesterol. Similarly mutation of aromatic residues in the caveolin-binding site abrogates AT(1)-R cell surface expression. In cells lacking caveolin-1 or caveolin-3, AT(1)-R does not traffic to the cell surface unless caveolin is ectopically expressed. This observation is recapitulated in caveolin-1 null mice that have a 55% reduction in renal AT(1)-R levels compared with controls. Taken together our results indicate that a direct interaction with caveolin is required to traffic the AT(1)-R through the exocytic pathway, but this does not result in AT(1)-R sequestration in caveolae. Caveolin therefore acts as a molecular chaperone rather than a plasma membrane scaffold for AT(1)-R.

Geometric isomers of chloro(6-methyl-1,4,8,11-tetraazacyclotetradecane-6-amine)cobalt(III) tetrachlorozincate(II)

The crystal structures of a pair of cis and trans isomers of the macrocyclic chloropentaamine title complex, as their tetrachlorozincate(II) salts, [CoCl(C11H27N5)][ZnCl4], are reported. The two distinct isomeric forms lead to significant variations in the Co-N bond lengths and, furthermore, hydrogen bonding between the complex ions is influenced by the folded (cis) or planar (trans) conformations of the coordinated ligand.

Low-temperature single-crystal Raman and neutron-diffraction study of the hydrogenous ammonium copper(II) tutton salt and the deuterated analogue in the metastable state

Low-temperature (15 K) single-crystal neutron-diffraction structures and Raman spectra of the salts (NX4)(2)[CU(OX2)(6)](SO4)(2), where X = H or D, are reported. This study is concerned with the origin of the structural phase change that is known to occur upon deuteration. Data for the deuterated salt were measured in the metastable state, achieved by application of 500 bar of hydrostatic pressure at similar to303 K followed by cooling to 281 K and the subsequent release of pressure. This allows for the direct comparison between the hydrogenous and deuterated salts, in the same modification, at ambient pressure and low temperature. The Raman spectra provide no intimation of any significant change in the intermolecular bonding. Furthermore, structural differences are few, the largest being for the long Cu-O bond, which is 2.2834(5) and 2.2802(4) Angstrom for the hydrogenous and the deuterated salts, respectively. Calorimetric data for the deuterated salt are also presented, providing an estimate of 0.17(2) kJ/mol for the enthalpy difference between the two structural forms at 295.8(5) K. The structural data suggest that substitution of hydrogen for deuterium gives rise to changes in the hydrogen-bonding interactions that result in a slightly reduced force field about the copper(II) center. The small structural differences suggest different relative stabilities for the hydrogenous and deuterated salts, which may be sufficient to stabilize the hydrogenous salt in the anomalous structural form.

Cytotoxic iron chelators: Characterization of the structure, solution chemistry and redox activity of ligands and iron complexes of the di-2-pyridyl ketone isonicotinoyl hydrazone (HPKIH) analogues

Di-2-pyridyl ketone isonicotinoyl hydrazone (HPKIH) and a range of its analogues comprise a series of monobasic acids that are capable of binding iron (Fe) as tridentate (N,N,O) ligands. Recently, we have shown that these chelators are highly cytotoxic, but show selective activity against cancer cells. Particularly interesting was the fact that cytotoxicity of the HPKIH analogues is maintained even after complexation with Fe. To understand the potent anti-tumor activity of these compounds, we have fully characterized their chemical properties. This included examination of the solution chemistry and X-ray crystal structures of both the ligands and Fe complexes from this class and the ability of these complexes to mediate redox reactions. Potentiometric titrations demonstrated that all chelators are present predominantly in their charge-neutral form at physiological pH (7.4), allowing access across biological membranes. Keto-enol tautomerism of the ligands was identified, with the tautomers exhibiting distinctly different protonation constants. Interestingly, the chelators form low-spin (diamagnetic) divalent Fe complexes in solution. The chelators form distorted octahedral complexes with Fe-II, with two tridentate ligands arranged in a meridional fashion. Electrochemistry of the Fe complexes in both aqueous and non-aqueous solutions revealed that the complexes are oxidized to their ferric form at relatively high potentials, but this oxidation is coupled to a rapid reaction with water to form a hydrated (carbinolamine) derivative, leading to irreversible electrochemistry. The Fe complexes of the HPKIH analogues caused marked DNA degradation in the presence of hydrogen peroxide. This observation confirms that Fe complexes from the HPKIH series mediate Fenton chemistry and do not repel DNA. Collectively, studies on the solution chemistry and structure of these HPKIH analogues indicate that they can bind cellular Fe and enhance its redox activity, resulting in oxidative damage to vital biomolecules.

Isomers of 1,4,8,11-tetraazacyclotetradecane-6,13-dicarboxylate characterized as cobalt(III) complexes

The major trans (1) and minor cis (2) isomers of 1,4,8,11-tetraazacyclotetradecane-6,13-dicarboxylate have been characterized as the complexes [Co(1)](ClO4) and [Co(H-2)(OH2)]Cl(ClO4).H2O. The former crystallized in the C-2/c space group and the latter in the P2(1)/c space group, with cell parameters a 16.258(7), b 9.050(3), c 15.413(6) Angstrom, beta133.29(3)degrees, and a 9.694(4), b 16.135(1), c 12.973(5) Angstrom, beta 93.00(2)degrees, respectively. Their characterization completes identification of the respective trans and cis isomers for the series of C-pendant macrocycles also including 1,4,8,11-tetraazacyclotetradecane-6-amine-13-carboxylate ((3), (4)) and 1,4,8,11-tetraazacyclotetradecane-6,13-diamine ((5), (6)). The complexes show limited distortion from octahedral geometry with the strain in the presence of the coordinated C-pendant carboxylate significantly reduced compared with that for the C-pendant amine in analogues, a consequence mainly of six-membered as opposed to five-membered chelate rings involving the pendant donor. A comparison of the physical properties for the trans isomers of the octahedral complexes of (1), (3), and (5), which reflect progressively increasing strain, is presented.

Scorpionate complexes as catalysts for alkane functionalization

A survey of the scorpionate tris(pyrazolyl)methane complexes synthesized by our group is presented, as well as their structural features and catalytic applications toward the funtionalization of linear and cyclic light alkanes.

Parte I: montagem do túnel pré-fabricado (Arco Techspan), localizado na variante do Cávado - Dolce Vita Braga: parte II: reabilitação e reparação das pontes sobre o rio Criz I e Criz II na E.N. 234

O presente relatório visa apresentar o trabalho desenvolvido pelo estagiário, na empresa Freyssinet -Terra Armada, SA. Este encontra-se dividido em 2 partes distintas. A primeira no âmbito da actividade Terra Armada, consistiu no acompanhamento da montagem do túnel pré-fabricado que estabelece a ligação entre a Rua C junto ao Centro Comercial Dolce Vita em Braga e a Variante do Cávado. A segunda no âmbito da actividade Freyssinet, consistiu no acompanhamento da obra de reabilitação e reforço estrutural de duas pontes denominadas de Criz I e Criz II, ambas localizadas na E.N.234 junto a Santa Comba Dão. A intensa ocupação dos terrenos em meio urbano leva cada vez mais ao estudo de novas soluções que permitem melhorar a circulação de pessoas e bens. Para restabelecer a ligação entre a Rua C e a Variante do Cávado a solução encontrada passou pela construção de um Túnel a céu aberto. Esta foi a melhor solução encontrada pois está prevista a intersecção de três vias denominadas de Variante do Cávado, Rua B e Rua D, todas relacionadas com os restabelecimentos de acesso ao empreendimento Dolce Vita Braga. Sobre as pontes de Criz I e Criz II recordamos que as mesmas foram projectadas em 1975 pelo Prof. Edgar Cardoso, tendo sido construídas no período que decorreu entre 1976 e 1979. Apesar de serem pontes recentes, estas apresentavam um avançado estado de deterioração o que levou à elaboração de um projecto específico de reparação e reforço estrutural e consequente intervenção, tendo sido adjudicadas à Freyssinet as intervenções concernentes ao reforço com Pré-Esforço, substituição de aparelhos de apoio e juntas de dilatação. O que mais adiante se detalhará no presente relatório será a explicação e descrição dos trabalhos executados em ambas as obras, onde foram aplicadas a tecnologia Terra Armada no primeiro caso e a tecnologia Freyssinet para o segundo caso.

Coordination Chemistry of the (eta(6)-p-Cymene)ruthenium(II) Fragment with Bis-, Tris-, andTetrakis(pyrazol-1-yl)borate Ligands: Synthesis, Structural, Electrochemical, and CatalyticDiastereoselective Nitroaldol Reaction Studies

Novel [Ru(eta(6)-p-cymene)(kappa(2)-L)X] and [Ru(eta(6)-p-cymene)(kappa(3)-L)]X center dot nH(2)O complexes (L = bis-, tris-, or tetrakis-pyrazolylborate; X = Cl, N-3, PF6, or CF3SO3) are prepared by treatment of [Ru(eta(6)-p-cymene)Cl-2](2) with poly-(pyrazolyl)borate derivatives [M(L)] (L in general; in detail L = Ph(2)Bp = diphenylbis-(pyrazol-1-yl)borate; L = Tp = hydrotris(pyrazol-1-yl)borate; L = pzTp = tetrakis(pyrazol-1-yl)borate; L = Tp(4Bo) = hydrotris(indazol-1-yl)borate, L = T-p4Bo,T-5Me = (5-methylindazol-1-yl)borate; L = Tp(Bn,4Ph) = hydrotris(3-benzyl-4-phenylpyrazol-1-yl)borate; M = Na, K, or TI) and characterized by analytical and spectral data (IR, ESIMS, H-1 and C-13 NMR). The structures of [Ru(eta(6)-p-cymene)(Ph(2)Bp)Cl] (1) and [Ru(eta(6)-p-cymene)(Tp)Cl] (3) have been established by single-crystal X-ray diffraction analysis. Electrochemical studies allowed comparing the electron-donor characters of Tp and related ligands and estimating the corresponding values of the Lever E-L ligand parameter. The complexes [Ru(eta(6)-p-cymene)-(kappa(2)-L)X] and [Ru(eta(6)-p-cymene)(kappa(3)-L)]X center dot nH(2)O act as catalyst precursors for the diastereoselective nitroaldol reaction of benzaldehyde and nitroethane to the corresponding beta-nitroalkanol (up to 82% yield, at room temperature) with diastereoselectivity toward the formation of the threo isomer.

Synthesis and structural characterization of iron complexes with 2,2,2-tris(1-pyrazolyl)ethanol ligands: Application in the peroxidative oxidation of cyclohexane under mild conditions

The reactions of FeCl2 center dot 2H(2)O and 2,2,2-tris(1-pyrazolyl) ethanol HOCH2C(pz)(3) (1) (pz = pyrazolyl) afford [Fe{HOCH2C(pz)(3)}(2)][FeCl4]Cl (2), [Fe{HOCH2C(pz)(3)}(2)](2)[Fe2OCl6](Cl)(2)center dot 4H(2)O (3 center dot 4H(2)O), [Fe{HOCH2C(pz)(3)}(2)] [FeCl{HOCH2C(pz)(3)}(H2O)(2)](2)(Cl)(4) (4) or [Fe{HOCH2C(pz)(3)}(2)]Cl-2 (5), depending on the experimental conditions. Compounds 1-5 were isolated as air-stable crystalline solids and fully characterized, including (1-4) by single-crystal X-ray diffraction analyses. The latter technique revealed strong intermolecular H-bonds involving the OH group of the scorpionate 2 and 3 giving rise to 1D chains which, in 3, are further expanded to a 2D network with intercalated infinite and almost plane chains of H-interacting water molecules. In 4, intermolecular pi center dot center dot center dot pi interactions involving the pyrazolyl rings are relevant. Complexes 2-5 display a high solubility in water (S-25 degrees C ca. 10-12 mg mL(-1)), a favourable feature towards their application as catalysts (or catalyst precursors) for the peroxidative oxidation of cyclo-hexane to cyclohexanol and cyclohexanone, with aqueous H2O2/MeCN, at room temperature (TON values up to ca. 385). (C) 2011 Elsevier B. V. All rights reserved.

Efficient cyclohexane oxidation with hydrogen peroxide catalysed by a C-scorpionate iron(II) complex immobilized on desilicated MOR zeolite

The hydrotris(pyrazol-1-yl)methane iron(II) complex [FeCl2{eta(3)-HC(pz)(3)}] (Fe, pz = pyrazol-1-yl) immobilized on commercial (MOR) or desilicated (MOR-D) zeolite, catalyses the oxidation of cyclohexane with hydrogen peroxide to cyclohexanol and cyclohexanone, under mild conditions. MOR-D/Fe (desilicated zeolite supported [FeCl2{eta(3)-HC(pz)(3)}] complex) provides an outstanding catalytic activity (TON up to 2.90 x 10(3)) with the concomitant overall yield of 38%, and can be easy recovered and reused. The MOR or MOR-D supported hydrotris(pyrazol-1-yl)methane iron(II) complex (MOR/Fe and MOR-D/Fe, respectively) was characterized by X-ray powder diffraction, ICP-AES, and TEM studies as well as by IR spectroscopy and N-2 adsorption at -196 degrees C. The catalytic operational conditions (e.g., reaction time, type and amount of oxidant, presence of acid and type of solvent) were optimized. (C) 2013 Elsevier B.V. All rights reserved.

Números curiosos: o favorito 7 (parte II)

Neste artigo, veremos mais algumas curiosidades relacionadas com o número 7. (...) Na China e em outros países asiáticos, o 7 é um número com profundas raízes mitológicas. Segundo um conhecido ritual, na sétima noite do sétimo mês do calendário lunar, as mulheres que procuram um bom casamento devem olhar para o céu sete vezes. (...) No dia 7 de julho de 2007 foram reveladas no estádio da Luz, em Lisboa, as Novas Sete Maravilhas do Mundo: as Ruínas de Petra na Jordânia, a Grande Muralha da China, o Cristo Redentor no Rio de Janeiro, o Coliseu em Roma, o Taj Mahal na Índia, o Chichén Itzá (cidade Maia) no México e o Machu Picchu (cidade perdida dos Incas) no Peru. Nesse mesmo dia, foram reveladas as Sete Maravilhas de Portugal: Castelo de Guimarães, Castelo de Óbidos, Mosteiro de Alcobaça, Mosteiro da Batalha, Mosteiro dos Jerónimos, Palácio da Pena e Torre de Belém. Em 2010, seguiu-se o anúncio das Sete Maravilhas Naturais de Portugal, que decorreu nas Portas do Mar, em Ponta Delgada. Duas delas são dos Açores: Paisagem Vulcânica da Ilha do Pico e Lagoa das Sete Cidades (...) Destacam-se algumas propriedades numéricas do 7: é o quarto número primo (depois do 2, 3 e 5) e o terceiro número de Mersenne. (...) O número 7 está bem presente nas nossas vidas, muito mais do que à primeira vista podemos pensar: sete são as cores do arco-íris (vermelho, laranja, amarelo, verde, azul, anil, violeta) e as notas musicais (dó, ré, mi, fá, sol, lá, si); na literatura infanto-juvenil, temos “A Branca de Neve e os Sete Anões” e a coleção “Os Sete” de Enid Blyton; e há ainda que ter em conta as sete vidas de um gato, os sete anos de azar para quem quebrar um espelho e os sete tipos de frisos que podemos encontrar nas nossas calçadas e varandas. (...)

Cobalt complexes with pyrazole ligands as catalyst precursors for the peroxidative oxidation of cyclohexane: Z-ray absorption spectroscopy studies and biological applications

[CoCl(-Cl)(Hpz(Ph))(3)](2) (1) and [CoCl2(Hpz(Ph))(4)] (2) were obtained by reaction of CoCl2 with HC(pz(Ph))(3) and Hpz(Ph), respectively (Hpz(Ph)=3-phenylpyrazole). The compounds were isolated as air-stable solids and fully characterized by IR and far-IR spectroscopy, MS(ESI+/-), elemental analysis, cyclic voltammetry (CV), controlled potential electrolysis, and single-crystal X-ray diffraction. Electrochemical studies showed that 1 and 2 undergo single-electron irreversible (CoCoIII)-Co-II oxidations and (CoCoI)-Co-II reductions at potentials measured by CV, which also allowed, in the case of dinuclear complex 1, the detection of electronic communication between the Co centers through the chloride bridging ligands. The electrochemical behavior of models of 1 and 2 were also investigated by density functional theory (DFT) methods, which indicated that the vertical oxidation of 1 and 2 (that before structural relaxation) affects mostly the chloride and pyrazolyl ligands, whereas adiabatic oxidation (that after the geometry relaxation) and reduction are mostly metal centered. Compounds 1 and 2 and, for comparative purposes, other related scorpionate and pyrazole cobalt complexes, exhibit catalytic activity for the peroxidative oxidation of cyclohexane to cyclohexanol and cyclohexanone under mild conditions (room temperature, aqueous H2O2). Insitu X-ray absorption spectroscopy studies indicated that the species derived from complexes 1 and 2 during the oxidation of cyclohexane (i.e., Ox-1 and Ox-2, respectively) are analogous and contain a Co-III site. Complex 2 showed low invitro cytotoxicity toward the HCT116 colorectal carcinoma and MCF7 breast adenocarcinoma cell lines.

Copper-organic frameworks assembled from in situ generated 5-(4-pyridyl) tetrazole building blocks: synthesis, structural features, topological analysis and catalytic oxidation of alcohols

Two new metal- organic compounds {[Cu-3(mu(3)-4-(p)tz)(4)(mu(2)-N-3)(2)(DMF)(2)](DMF)(2)}(n) (1) and {[Cu(4ptz) (2)(H2O)(2)]}(n) (2) {4-ptz = 5-(4-pyridyl)tetrazolate} with 3D and 2D coordination networks, respectively, have been synthesized while studying the effect of reaction conditions on the coordination modes of 4-pytz by employing the [2 + 3] cycloaddition as a tool for generating in situ the 5-substituted tetrazole ligands from 4-pyridinecarbonitrile and NaN3 in the presence of a copper(II) salt. The obtained compounds have been structurally characterized and the topological analysis of 1 discloses a topologically unique trinodal 3,5,6-connected 3D network which, upon further simplification, results in a uninodal 8-connected underlying net with the bcu (body centred cubic) topology driven by the [Cu-3(mu(2)-N-3)(2)] cluster nodes and mu(3)-4-ptz linkers. In contrast, the 2D metal-organic network in 2 has been classified as a uninodal 4-connected underlying net with the sql [Shubnikov tetragonal plane net] topology assembled from the Cu nodes and mu(2)-4-ptz linkers. The catalytic investigations disclosed that 1 and 2 act as active catalyst precursors towards the microwave-assisted homogeneous oxidation of secondary alcohols (1-phenylethanol, cyclohexanol, 2-hexanol, 3-hexanol, 2-octanol and 3-octanol) with tert-butylhydroperoxide, leading to the yields of the corresponding ketones up to 86% (TOF = 430 h(-1)) and 58% (TOF = 290 h(-1)) in the oxidation of 1-phenylethanol and cyclohexanol, respectively, after 1 h under low power ( 10 W) microwave irradiation, and in the absence of any added solvent or additive.

Diethydithiocarbamate complexes with metals used as food suplements show diferente effects in cancer cells

Diethyldithiocarbamate (ditiocarb), a metabolite of the old anti-alcoholic drug disulfiram (Antabuse), forms proteasome-inhibiting metal complexes with copper or zinc that suppress cancer cells both in vitro and in vivo. The drug has been used in a clinical trial (NCT00742911) along with copper gluconate as a dietary supplement in patients with cancer spreading to the liver. In this study, we demonstrate the effect of synthetic complexes of disulfiram with four various metals (Mn, Fe, Cr and Cu) used as food supplements. These complexes may be spontaneously formed in the blood during the use of disulfiram with divalent metals and thus may suppress the growth of cancer in vivo. The cytotoxic effect of the compounds and the compounds' ability to inhibit the cellular proteasome were tested in the osteosarcoma cell line U2OS. After 48 h, copper and manganese complexes exhibited cytotoxic effect on the cell line, in sharp contrast to both iron and chromium complexes. (C) 2014 Faculty of Health and Social Studies, University of South Bohemia in Ceske Budejovice. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.