N-H...S=C hydrogen bond in O-alkyl N-methoxycarbonyl thiocarbamates, ROC(S)N(H)C(O)O)CH(3) (R = CH(3)(-), CH(3)CH(2)-)

Pure O-methyl N-methoxycarbonyl thiocarbamate CH(3)OC(S)N(H)C(O)OCH(3) (I) and O-ethyl N-methoxycarbonyl thiocarbamate, CH(3)CH(2)OC(S)N(H)C(O)OCH(3) (II), are quantitatively prepared by the addition reaction between the CH(3)OC(O)NCS and the corresponding alcohols. The compounds are characterized by multinuclear ((1)H and (13)C) and bi-dimensional ((13)C HSQC) NMR, GC-MS and FTIR spectroscopy techniques. Structural and conformational properties are analyzed using a combined approach involving crystallographic data, vibration spectra and theoretical calculations. The low-temperature (150 K) crystal structure of II was determined by X-ray diffraction methods. The substance crystallizes in the monoclinic space group P2(1)/n with a = 4.088(1)angstrom. b = 22.346(1)angstrom, c = 8.284(1)angstrom, beta = 100.687(3)degrees and Z = 4 molecules per unit cell. The conformation adopted by the thiocarbamate group -OC(S)N(H)- is syn (C=S double bond in synperiplanar orientation with respect to the N-H single bond), while the methoxycarbonyl C=O double bond is in antiperiplanar orientation with respect to the N-H bond. The non-H atoms in II are essentially coplanar and the molecules are arranged in the crystal lattice as centro-symmetric dimeric units held by N-H center dot center dot center dot S=C hydrogen bonds Id(N center dot center dot center dot S) = 3.387(1)angstrom, <(N-H center dot center dot center dot S) = 166.4(2)degrees]. Furthermore, the effect of the it electronic resonance in the structural and vibrational properties is also discussed. (C) 2009 Elsevier Ltd. All rights reserved.

Structural effects and hydrogen bonds on N,N `-di(methoxycarbonylsulfenyl)urea, [CH(3)OC(O)SNH](2)CO, studied by experimental and theoretical methods

Pure N,N`-di(methoxycarbonylsulfenyl)urea, [CH(3)OC(O)SNH](2)CO, is quantitatively prepared by the hydrolysis reaction of CH(3)OC(O)SNCO and characterized by (1)H NMR, GC-MS and FTIR spectroscopy techniques. Structural and conformational properties are analyzed using a combined approach with data obtained from X-ray diffraction, vibrational spectra and theoretical calculation methods. The IR and Raman spectra for normal and deuterated species are reported. The crystal structure of [CH(3)OC(O)SNH](2)CO was determined by X-ray diffraction methods. The substance crystallizes in the orthorhombic P2(1)2(1)2 space group with a = 9.524(2), b = 12.003(1), c = 4.481 (1) angstrom, and Z = 2 moieties in the unit cell. The molecule is sited on a twofold crystallographic axis (C(2)) parallel to c and shows the anti-anti conformation (S-N single bonds antiperiplanar with respect to the opposite C-N single bonds in sulfenyl-urea-sic group). Neighboring molecules are arranged in a chain motif that extends along the C(2)-axis and is held by bifurcated NH center dot center dot center dot O center dot center dot center dot HN intermolecular bonds. A local planar symmetry is observed in the crystal for the central -SN(H)C(O)N(H)S- skeleton. Experimental and calculated data allow to trace this structural feature to the occurrence of N-H center dot center dot center dot O=C hydrogen bonding interactions. Calculated vibrational and structural properties are in good agreement with the experimentally determined features. (C) 2008 Elsevier B.V. All rights reserved.

Structure and thermal reactivity of Zn(II) salts of isocinchomeronic acid (2,5-pyridinedicarboxylic acid)

The synthesis, an improved refined crystal and molecular structure re-determination, and the thermal decomposition behavior of two Zn(II) derivatives of isocinchomeronic acid (2,5-pyridinedicarboxylic acid or H(2)2,5-pydc) are presented. [Zn(2,5-pydc)(H(2)O)(3)Zn(2,5-pydc)(H(2)O)(2)](2) (1) crystallizes in the triclinic P-1 space group with a = 7.106(2), b = 11.450(2), c = 11.869(1) angstrom, alpha = 107.29(1), beta = 104.08(1), gamma = 90.32(2)degrees, and Z = 2. [Zn(2,5-pydc)(H(2)O)(2)] center dot H(2)O (2) is orthorhombic (P2(1)2(1)2(1) space group), with a = 7.342(1), b = 9.430(1), c = 13.834(2) angstrom, and Z = 4. The structures were refined to agreement R(1)-factors of 0.0315 (1) and 0.0336 (2). Complex (1) is arranged as molecular Zn(4)(2,5-pydc)(4)(H(2)O)(10) tetramers, the cages of which define channels that remain unblocked by anions. Compound (2) is polymeric with Zn(2,5-pydc)(H(2)O)(2) and Zn(2,5-pydc)(H(2)O)(3) units linked through bridging ligands. Both compounds were synthesized under mild conditions in aqueous media, without need to resort to hydrothermal media. Changing the pH from 4.51 to 5.75 suffices to direct the chemical processes toward the orthorhombic compound rather than to the triclinic one.

Oxorhenium(V) Complexes with 2,3-Dihydroxynaphthalene

2,3-Dihydroxynaphthalene (H(2)dhn) reacts with [ReOCl(3)-(PPh(3))(2)] or [ReOBr(3)(PPh(3))(2)] in a 1:1 molar ratio with formation of the isostructural complexes [ReOCl(2)(PPh(3))(2)(Hdhn)] (4) and [ReOBr(2)-(PPh(3))(2)(Hdhn)] (5). They have distorted octahedral coordination spheres with the halide and the triphenylphosphine ligands arranged in equatorial trans positions to each other. The Hdhn-ligand coordinates monodentately in trans position to the oxo ligand. Intramolecular hydrogen bonds between the Hdhn and the halogeno ligands stabilize this coordination mode. The products represent the first examples of oxorhenium(V) complexes with monodentate catecholate-type ligands.

Organização de uma bateria de testes para seleção de candidatos ao ensino técnico de 2. grau

O trabalho aqui apresentado relata um estudo exploratório na área de Educação Técnico-Industrial de segundo grau, cujo objetivo consistiu em selecionar, dentre vários testes, os que fossem melhores preditores do aproveitamento acadêmico dentro da formarão profissional, para formar parte da bateria de testes que serão utilizadas na seleção dos candidatos aos cursos oferecidos pelo Colégio Técnico Nacional para a formação de técnicos de nível médio. o estudo em apreço, realizado mediante a colaboração entre o Departamento de Educação Técnica e o Departamento de Orientação Educacional e Vocacional, ambos do Ministério de Educa9ão e Cultura do Paraguai, é parte do projeto de expansão da orientação no nível de Formação Técnico-Industrial e Formação Profissional do qual um dos objetivos é controlar a qualidade da matricula a fim de evitar a evasão e favorecer o maior aproveitamento destes cursos oferecidos a este nível, o que será possível através da implantarão, em todos os Colégios desde tipo, de medidas de avaliação de aptidões e interesses para o desenvolvimento dos recursos humanos dos países em desenvolvimento. Partiu-se de uma análise minuciosa dos programas de estudo das matérias que compunham a bagagem de cada especialidade, com a finalidade de realizar uma lista de aptidões e traços que compõe a especificação profissional de cada especialidade. Foram experimentados 13 testes psicométricos, um de interesses ocupacionais e dois de personalidade. Dos quais após submetidos ao tratamento estadístico para conhecer sua precisão e validade em relação a um critério (o rendimento acadêmico nas matérias da especialidade) foram selecionados os seguintes testes: I N V de Pierre Weil, Raciocínio espacial Ribakow, Rapidez e exatidão no cálculo da bateria CEPA, Teste de Destreza Manual e Atenção distribuída e o Raciocínio Mecânico do DAT por ser os de melhor índice de precisão e validade (elevada correlação com as mate rias profissionais das especialidades). Este estudo se constitui no passo inicial para a elaboração de outros sistemas de seleção de matrícula baseados em provas pSicol6gicas, organizados pela Unidade de Psicometria e Psicologia Escolar de Dpto. de Orientação Educativa e Vocacional do M. E. C.

Pesquisa orientada a resultado : proposta de um método estruturado para disponibilizar uma nova tecnologia para o mercado : um caso aplicado ao projeto etanol de 2ª geração

Esta dissertação de mestrado teve como objetivo principal propor um método estruturado suportado for ferramentas gerenciais que permitisse orientar e sistematizar o desenvolvimento de um projeto de pesquisa na disponibilização de uma nova tecnologia para o mercado. O “Projeto Etanol de 2ª Geração”, etanol produzido a partir de biomassas lignocelulósicas, aqui selecionado para estudo de caso, foi extraído da carteira de projetos do Centro de Tecnologia Canavieira (CTC). O método estruturado sugerido é constituído, fundamentalmente, por oito requisitos arranjados de forma cronológica ao longo do desenvolvimento do projeto, que visam auxiliar na prospecção, entendimento, avaliação, valoração, priorização, planejamento e implantação de, por exemplo, uma tecnologia inovadora, otimizando tempo, capital e recursos humanos aplicados. Um dos principais pontos do método proposto refere-se à escolha adequada das ferramentas gerenciais a serem utilizadas em cada requisito (brainstorm, análise de patentes, painel de especialistas, análise SWOT, dentre outras). O êxito na aplicação do método requer o entendimento de todos os (potenciais) efeitos, inclusive os colaterais, no processo como um todo. Ou seja, uma vez que toda ferramenta gerencial apresenta pontos fortes e fracos, o importante é adaptá-las ao sistema de negócio e não vice-versa. A partir do gerenciamento do projeto por um gestor com domínio das ferramentas gerenciais, a escolha destas ocorre de forma dinâmica, onde a cada passo de avaliação novas ferramentas (simples e/ou complexas) podem ser incluídas ou excluídas da matriz do método. Neste trabalho ficou demonstrada a importância de se trabalhar com métodos estruturados e flexíveis, que permitem retroalimentação de informações geradas internamente durante o desenvolvimento da pesquisa ou advindas de fontes externas. O projeto Etanol de 2ª Geração do CTC vem aplicando o método proposto em seu desenvolvimento e obtendo grande êxito em seus resultados, uma vez que a equipe envolvida permanece focada no objetivo principal, obedecendo prazos e recursos inicialmente definidos, com constância do propósito do projeto, sem retrocesso ou recomeço.

Influência da chuva na eficácia do herbicida 2,4-D no controle de Myriophyllum aquaticum

O objetivo deste estudo foi avaliar a eficiência de controle de duas doses do herbicida 2,4-D pulverizado em plantas de M. aquaticum e submetido à simulação de chuva em diferentes períodos de tempo após sua aplicação. O delineamento experimental utilizado foi o inteiramente casualizado, com quatro repetições, disposto em um esquema fatorial 2 x 8 (duas doses de herbicida e oito intervalos de chuva). Utilizou-se o herbicida 2,4-D, na formulação comercial DMA 806, em duas doses: 670 e 1.340 g e.a. ha-1. A simulação de uma chuva de 15 mm, com duração de cinco minutos, foi realizada em oito intervalos de tempo após a pulverização do herbicida (0,25h, 0,5h, 1h, 2h, 4h, 8h, 12h e sem chuva). Foram realizadas avaliações visuais de controle aos 7, 14, 21 e 28 dias após a aplicação dos tratamentos. As duas doses avaliadas do herbicida 2,4-D foram eficientes no controle das plantas de M. aquaticum, mesmo com ocorrência de chuva 15 minutos após sua aplicação.

Spectroscopic, Structural, and Conformational Properties of (Z)-4,4, 4-Trifluoro-3-(2-hydroxyethylamino)-1-(2-hydroxypheny1)-2-buten-1-one, C12H12F3NO3: A Trifluoromethyl-Substituted beta-Aminoenone

The ( Z)-4,4,4-trifluoro-3-(2-hydroxyethylamino)-1-(2-hydroxyphenyl)-2-buten-1-one (C12H12F3NO3) compound was thoroughly studied by IR, Raman, UV-visible, and C-13 and F-19 NMR spectroscopies. The solid-state molecular structure was determined by X-ray diffraction methods. It crystallizes in the P2(1)/c space group with a = 12.1420(4) angstrom, b = 7.8210(3) angstrom, c := 13.8970(5) angstrom, beta = 116.162(2)degrees, and Z = 4 molecules per unit cell. The molecule shows a nearly planar molecular skeleton, favored by intramolecular OH center dot center dot center dot 0 and NH center dot center dot center dot 0 bonds, which are arranged in the lattice as an OH center dot center dot center dot 0 bonded polymer coiled around crystallographic 2-fold screw-axes. The three postulated tautomers were evaluated using quantum chemical calculations. The lowest energy tautomer (I) calculated with density functional theory methods agrees with the observed crystal structure. The structural and conformational properties are discussed considering the effect of the intra- and intermolecular hydrogen bond interactions.

Conformational preferences for some 3-(4 '-substituted phenylsulfonyl)-1-methyl-2-piperidones through spectroscopic and theoretical studies

The analysis of the infrared (IR) carbonyl band of some 3-(4'-substituted phenylsulfonyl)-1-methyl-2-piperidones 1-5 bearing as substituents: OMe 1, Me 2, H 3, Cl 4 and NO2 5, supported by B3LY13/6-31G(d,p) calculations along with NBO analysis (for 1, 3 and 5) and X-ray diffraction (for 5), indicated the existence of three stable conformations i.e. quasi-axial (q-ax), syn-clinal (s-cl) and quasi-equatorial (q-eq). In the gas phase, the q-ax conformer is calculated as the most stable (ca. 88%) and the least polar, the s-cl conformer is less stable (ca. 12%) but more polar, and the q-eq conformer is the least stable (ca. 1%) and the most polar of the three conformers evaluated. The sum of the most important orbital interactions from NBO analysis and the trend of the electrostatic interactions accounts for the relative populations as well as for the v(CO) frequencies of the q-ax. s-cl and q-eq conformers calculated in the gas phase. The unique IR v(CO) band in CCl4 may be ascribed to the most stable q-ax conformer. The more intense (60%) high frequency doublet component in CHCl3 may be assigned to the summing up of the least stable q-eq and the less stable s-cl conformers, as their frequencies are almost coincident. The occurrence of only a single v(CO) band in both CH2Cl2 and CH3CN supports the fact that the v(CO) band of the two more polar conformers appear as a single band. Additional support to this rationalization is given by the single point PCM method, which showed a progressive increase of the q-eq + s-cl/q-ax population ratio going from the gas phase to CCl4, to CHCl3, to CH2Cl2 and to CN3CN. X-ray single crystal analysis of 5 indicates that this compound displays a quasi-axial geometry with respect to the [O=C-CH-S] moiety, and that the 2-piperidone ring assumes a slightly distorted half-chair conformation. In the crystal packing, molecules of 5 are arranged into supramolecular layers linked through C-H center dot center dot center dot O interactions along with it pi center dot center dot center dot pi interactions between adjacent benzene rings. (C) 2012 Elsevier B.V. All rights reserved.

Selektiv deblockierbare 2,6-Diamino-2,6-didesoxy-D-glucose-Scaffolds für die kombinatorische Synthese potentieller RNA-Liganden

Aminoglydosid-Antibiotika wie Neomycin B oder Cyclopeptid-Antibiotike wie Viaomycin sind dafür bekannt, daß sie selektiv an RNA binden können. Diese Interaktionen beruhen sowohl auf elektrostatischen Wechselwirkungen als auch auf H-Brücken-Bindungen. Des weiteren ist die definierte räumliche Anordnung von Donor- und Akzeptor-Resten in den Strukturen der RNA-Liganden wichtig für die Affinität. Eine Möglichkeit natürliche RNA-Liganden zu imitieren ist der Einsatz polyfunktioneller Template wie zum Beispiel das 2,6-Diamino-2,6-didesoxy-D-glucose-Scaffold. Mit Hilfe dieser Scaffolds können dann verschiedene positv geladene Reste und Donatoren sowie Akzeptoren für H-Brücken-Bindungen oder auch Interkalatoren räumlich definiert präsentiert werden. Für die unabhängige Funktionalisierung einer jeden Position ist ein Satz orthogonal stabiler Schutzgruppen nötig, wobei eine Hydroxylguppe durch einen Anker ersetzt wird, der eine Anbindung des Scaffolds an einen polymeren Träger ermöglicht. Das neu entwickelte 2,6-Diamino-2,6-didesoxy-D-glucose-Scaffold ist das erste Monosaccharid-Templat, das in allen fünf Positionen mit orthogonal stabilen Schutzgruppen blockiert ist. Alle Positionen könne in beliebiger Reihenfolge selektiv deblockiert und anschließend derivatisiert werden. Das Scaffold kann mit Aminosäuren, Guanidinen oder Interkalatoren umgesetzt werden, um so natürlich vorkommende RNA-bindende Aminoglycoside oder Peptide zu imitieren. Aufbauend auf diesem Monosaccharid-Templat wurde eine Bibliothek von über 100 potentiellen RNA-Liganden synthetisiert, die im Rahmen des Sonderforschungsbereichs 579 (RNA-Liganden-Wechselwirkungen) in Zellassays auf ihre Fähigkeit zur Hemmung der Tat/TAR-Wechselwirkung untersucht wurden, wobei bis jetzt 9 Verbindungen mit einer hemmenden Wirkung im micromolaren Bereich gefunden wurden.

Development of a highly potent bispecific antibody format targeting the novel tumor-specific antigen CLDN18.2

Due to multiple immune evasion mechanisms of cancer cells, novel therapy approaches are required to overcome the limitations of existing immunotherapies. Bispecific antibodies are potent anti-cancer drugs, which redirect effector T cells for specific tumor cell lysis, thus enabling the patient’s immune system to fight cancer cells. The antibody format used in this proof of concept study–bispecific ideal monoclonal antibodies termed BiMAB–is a tailor-made recombinant protein, which consists of two fused scFv antibodies recognizing different antigens. Both are arranged in tandem on a single peptide chain and the individual variable binding domains are separated by special non-immunogenic linkers. The format is comprised of a scFv targeting CLDN18.2–a gastric cancer tumor associated antigen (TAA) –while the second specificity binds the CD3 epsilon (CD3ε) subunit of the T cell receptor (TCR) on T cells. For the first time, we compared in our IMAB362-based BiMAB setting, four different anti-CD3-scFvs, respectively derived from the mAbs TR66, CLB-T3, as well as the humanized and the murine variant of UCHT1. In addition, we investigated the impact of an N- versus a C-terminal location of the IMAB362-derived scFv and the anti-CD3-scFvs. Thus, nine CLDN18.2 specific BiMAB proteins were generated, of which all showed a remarkably high cytotoxicity towards CLDN18.2-positive tumor cells. Because of its promising effectiveness, 1BiMAB emerged as the BiMAB prototype. The selectivity of 1BiMAB for its TAA and CD3ε, with affinities in the nanomolar range, has been confirmed by in vitro assays. Its dual binding depends on the design of an N-terminally positioned IMAB362 scFv and the consecutive C-terminally positioned TR66 scFv. 1BiMAB provoked a concentration and target cell dependent T cell activation, proliferation, and upregulation of the cytolytic protein Granzyme B, as well as the consequent elimination of target cells. Our results demonstrate that 1BiMAB is able to activate T cells independent of elements that are usually involved in the T cell recognition program, like antigen presentation, MHC restriction, and co-stimulatory effector molecules. In the first in vivo studies using a subcutaneous xenogeneic tumor mouse model in immune incompetent NSG mice, we could prove a significant therapeutic effect of 1BiMAB with partial or complete tumor elimination. The initial in vitro RIBOMAB experiments correspondingly showed encouraging results. The electroporation of 1BiMAB IVT-RNA into target or effector cells was feasible, while the functionality of translated 1BiMAB was proven by induced T cell activation and target cell lysis. Accordingly, we could show that the in vitro RIBOMAB approach was applicable for all nine BiMABs, which proves the RIBOMAB concept. Thus, the CLDN18.2-BiMAB strategy offers great potential for the treatment of cancer. In the future, administered either as protein or as IVT-RNA, the BiMAB format will contribute towards finding solutions to raise and sustain tumor-specific cellular responses elicited by engaged and activated endogenous T cells. This will potentially enable us to overcome immune evasion mechanisms of tumor cells, consequently supporting current solid gastric cancer therapies.

The crystal structure of the platelet activator aggretin reveals a novel (alphabeta)2 dimeric structure

Aggretin is a C-type lectin purified from Calloselasma rhodostoma snake venom. It is a potent activator of platelets, resulting in a collagen-like response by binding and clustering platelet receptor CLEC-2. We present here the crystal structure of aggretin at 1.7 A which reveals a unique tetrameric quaternary structure. The two alphabeta heterodimers are arranged through 2-fold rotational symmetry, resulting in an antiparallel side-by-side arrangement. Aggretin thus presents two ligand binding sites on one surface and can therefore cluster ligands in a manner reminiscent of convulxin and flavocetin. To examine the molecular basis of the interaction with CLEC-2, we used a molecular modeling approach of docking the aggretin alphabeta structure with the CLEC-2 N-terminal domain (CLEC-2N). This model positions the CLEC-2N structure face down in the "saddle"-shaped binding site which lies between the aggretin alpha and beta lectin-like domains. A 2-fold rotation of this complex to generate the aggretin tetramer reveals dimer contacts for CLEC-2N which bring the N- and C-termini into the proximity of each other, and a series of contacts involving two interlocking beta-strands close to the N-terminus are described. A comparison with homologous lectin-like domains from the immunoreceptor family reveals a similar but not identical dimerization mode, suggesting this structure may represent the clustered form of CLEC-2 capable of signaling across the platelet membrane.

Highly Efficient Non-palladium Catalyzed Controlled Synthesis and X-ray Analysis of Functionalized 1,2-Diaryl-, 1,2,3-Triaryl- and 1,2,3,4-Tetraarylbenzene

A general, two-step highly efficient synthesis of 1,2-diaryl-, 1,2,3-triaryl- and 1,2,3,4-tetraarylbenzenes from simple stitching of alpha-oxo-ketene-S,S-acetals and active methylene compounds via a ‘lactone intermediate’ is described. This procedure offers easy access to highly functionalized arylated-benzenes containing sterically demanding groups in good to excellent yields. The novelty of the procedure lies in the fabrication of aromatic compounds with desired conformational flexibility along the molecular axis in a transition metal-free environment through easily accessible precursors. The crystal analysis of these arylated-benzene scaffolds showed that the peripheral aryl rings are arranged in propeller-like fashion with respect to the central benzene rings. Examination of the crystal packing in the structure of a 1,2,3,4-tetraarylbenzene 12c revealed a “N…pi interaction” between molecules related by a two-fold screw axis running in a direction. It is interesting that the repeat of the array of N…pi interaction around the axis of the 1,2,3,4-tetraarylbenzene 12c enforces the molecules in a helical pattern.

England under the heel of the Jew : a tale of 2 books

arranged by the author of "The Call of the sword" [d.i. John Henry Clarke]

A Lexicon, Hebrew, Chaldae, and English, compiled from the most approved sources, Oriental and European, Jewish and Christian ... cont. all the words with their usual inflexions ... as found in the Hebrew and Chaldee texts of the Old Testament ... to which are added an English index, alphabetically arranged ...

by Samuel Lee