It was proposed to study the cycloaddition of ketenes and carbodiimides in some detail. The first objective was to investigate the general applicability of the reaction as a tool for the synthetic organic chemist in the preparation of a new class of substituted β-lactams; i.e., imino-β-lactams. It was proposed for this part of the research problem to look for the intermediate, either directly or indirectly, by trapping experiments. It was further proposed to study substituent effects in the ketene and carbodiimide and also Investigate the effect of solvent polarity on the reaction rate. From these data, it was hoped that the mechanism of the cycloaddition reaction could be elucidated.

Trimethylsilylbromoketene was synthesized by the tri-ethylamine dehydrohalogenation of trimthylsilylbromacetyl bromide or chloride. This ketene was found not to undergo cycloaddition reactions with activated olefins, such as cyclopentadiene, ethyl vinyl ether and dihydropyan.

The ATPase complex of E. coll consists of two functional units. ECF[sub=1] is an extrinsic membrane protein having the active site(s) for ATP synthesis and hydrolysis. F₀ is intrinsic and catalyzes the reversible transfer of protons across the membrane. ECF[sub=1] consists of five polypeptides (α- ε) ranging in molecular weight from 13 000 - 57 000. F₀ has three polypeptides (9 000, 18 000, 24 000), the smallest of which is the dicyclohexylcarbodiimide (DCCD)-binding protein postulated to be a transmembrane pathway for proton translocation. An ECF₁F₀ complex was solubilized from the membranes of E. coli with N-lauroyl sarcosine and purified by chromatography on Phenyl-Sepharose CL-4B followed by sedimentation of the enzyme at 250 000 xg for 16-17 h. The purified ECF₁F₀ complex consisted of the eight polypeptides described above, as well as associated polypeptides of molecular weights 30 000, 28 000 and 14 000. Removal of ECF₁ from the membranes of the wild-type E. coli resulted in the membranes becoming leaky to protons so that they could not be energized. The unc mutants, E. coli AN382, CBT-302 and N₁₄₄ could maintain a proton gradient across the membrane in the absence of ECF₁. A normal DCCD-binding protein was present in the F₀ complex of each mutant. However, the 18 000 dalton polypeptide of F₀ was absent in the membranes of E. coli N₁₄₄, suggesting that it was required for a functional F₀. The involvement of the 18 000 dalton polypeptide in the proton-translocating activity was also suggested by the observation that this polypeptide was absent in the ECF₁F₀ complex immunoprecipitated from trypsin-treated "stripped" vesicles, which had been reconstituted with ECF₁. Although these trypsin-treated "stripped" vesicles could rebind ECF₁, the membranes could not be energized during ATP hydrolysis. Leakiness of the membranes to protons could be repaired by the reaction of the ECF₁ stripped membranes with DCCD or ECF₁. Similarly, antibody raised against the DCCD-binding protein prevented this leakage of protons. The antibody also inhibited the rebinding of ECF₁ to the "stripped" everted membrane vesicles. These results indicated that the DCCD-binding protein was exposed on the cytoplasmic surface of the cell. Attempts to show whether the DCCD-binding protein was transmembranous were not successful. Radioimmunoassay techniques were used to show In vitro, the involvement of the arginyl residue(s) of the DCCD-binding protein in the binding of ECF₁. Binding of ECF₁ to the DCCD-binding protein appeared to involve the α and/or β subunits of ECF₁. Chemical modification of the methionyl residue(s) of the DCCD-binding protein did not alter its capacity to bind ECF₁, but destroyed the antigenic site(s) of the polypeptide. In summary, these results are consistent with the proposed "loop" arrangement of the DCCD-binding protein in which the polar central region of this molecule is at the cytoplasmic surface of the cell membrane. / Medicine, Faculty of / Biochemistry and Molecular Biology, Department of / Graduate

The 1,3-diaza Claisen rearrangement was initially discovered by the Madalengoitia group in the early 2000s. Tertiary, allylic, amines nucleophilically add to the carbon of a heterocumulene (isocyanate, isothiocyanate, or carbodiimide) to generate a zwitterion which then undergoes [3,3]-sigmatropic rearrangement. The rearrangements conducted with a carbodiimide generate guanidine-containing skeletons. The guanidine functional group is found in many biologically active products, making it a worthwhile chemical target. To this end, strained, tertiary, allylic, amine 2-benzyl-2-azabicyclo[2.2.1]hept-5-ene reacts with in-situ generated carbodiimides in the 1,3-diaza-Claisen rearrangement to afford structurally interesting bicyclic guanidines. Use of more electron deficient carbodiimides makes these rearrangements more facile; however, there are not sufficient methods for the synthesis of highly electron deficient carbodiimides. The synthesis of such carbodiimides was explored through new synthetic methodologies for the dehydration of ureas and desulfurization of isothioureas and the carbodiimides were used in a series of intermolecular rearrangements with the strained, tertiary, allylic, amine. The new methodologies for the synthesis of electron deficient carbodiimides were then applied to a series of intramolecular substrates, further expanding the 1,3-diaza Claisen rearrangement methodologies. To date series of bicyclic, tricyclic, and monocyclic guanidines of varying structures have been synthesized. The synthetic efforts towards these products are herein described.

Thesis (M.A.) - Carleton University, 2007. / Includes bibliographical references (p. 59-60). Also available in electronic format on the Internet.

No description available.

Ao contrário da percepção da sociedade em geral, a tuberculose ainda é uma das mais graves doenças infecciosas da atualidade, estando à frente da HIV/AIDS como uma das maiores causas de morte por infecção. Apesar de todos os avanços recentes, o aparecimento de cepas multirresistentes não permitiu sua erradicação. Em 2016, a OMS lançou novos alvos rumo à erradicação global da enfermidade (End TB), alvos estes que, no Brasil, foram divulgados no Plano Nacional pelo Fim da TB, do Ministério da Saúde. Para que estas metas possam ser atingidas, a pesquisa em busca de novos fármacos, que possam diminuir o tempo de tratamento e seus efeitos adversos, tem papel fundamental. Modelagem molecular e planejamento racional otimizam a busca das novas drogas potenciais. Assim, modelos de QSAR aliados a metodologias de planejamento de fármacos auxiliados por computador (CADD) foram usados para a proposição das moléculas que se tornaram o alvo da síntese deste trabalho. Dois procedimentos distintos foram utilizados para sintetizar 1-H-2-aminoindol a partir de orto-cloronitrobenzeno. Paralelamente, quatro ácidos succinâmicos foram preparados pela reação de anidrido succínico com diferentes aminas. Posteriormente, cada ácido succinâmico deveria ser acoplado ao 1-H-2-aminoindol por meio de agentes de acoplamento como as carbodiimidas. Os resultados obtidos indicam que DCC em diclorometano pode ser eficiente para a síntese dos potenciais novos fármacos. / Contrary to popular belief, tuberculosis TB is still one of the most serious of infectious diseases today, surpassing AIDSHIV as one of the major causes of death by infection. ln spite of recent advances, the appearance of multi-resistant strains prevents its eradication. ln 2016, the OMS launched new geais for global eradication of the disease (End TB), geais that, in Brazil, were disclosed through the \"National Planto End TB,\" from the Ministry of Health. ln arder to reach these geais, studies in search of new anti-mycobacterials that could lessen the treatment time and its adverse effects have a fundamental role. Molecular modeling and rational planning optimize the search for new potential drugs. Thus, QSAR models in line with computer-aided drug design (CADD) were used for the molecule proposition that became the synthesis target of this work. Two distinct proceedings were utilized to synthesize 1-H-2-aminoindole from the ortho-chloronitrobenzene. Simultaneously, four succinamic acids were prepared by the reaction of succinic anhydride with different amines. Posteriorly, each succinamic acid should be coupled with 1-H-2-aminoindole by way of coupling agents such as carbodiimides. The results obtained indicate that DCC in dichloromethane can be efficient for the synthesis of potential new drugs.

Ao contrário da percepção da sociedade em geral, a tuberculose ainda é uma das mais graves doenças infecciosas da atualidade, estando à frente da HIV/AIDS como uma das maiores causas de morte por infecção. Apesar de todos os avanços recentes, o aparecimento de cepas multirresistentes não permitiu sua erradicação. Em 2016, a OMS lançou novos alvos rumo à erradicação global da enfermidade (End TB), alvos estes que, no Brasil, foram divulgados no Plano Nacional pelo Fim da TB, do Ministério da Saúde. Para que estas metas possam ser atingidas, a pesquisa em busca de novos fármacos, que possam diminuir o tempo de tratamento e seus efeitos adversos, tem papel fundamental. Modelagem molecular e planejamento racional otimizam a busca das novas drogas potenciais. Assim, modelos de QSAR aliados a metodologias de planejamento de fármacos auxiliados por computador (CADD) foram usados para a proposição das moléculas que se tornaram o alvo da síntese deste trabalho. Dois procedimentos distintos foram utilizados para sintetizar 1-H-2-aminoindol a partir de orto-cloronitrobenzeno. Paralelamente, quatro ácidos succinâmicos foram preparados pela reação de anidrido succínico com diferentes aminas. Posteriormente, cada ácido succinâmico deveria ser acoplado ao 1-H-2-aminoindol por meio de agentes de acoplamento como as carbodiimidas. Os resultados obtidos indicam que DCC em diclorometano pode ser eficiente para a síntese dos potenciais novos fármacos. / Contrary to popular belief, tuberculosis TB is still one of the most serious of infectious diseases today, surpassing AIDSHIV as one of the major causes of death by infection. ln spite of recent advances, the appearance of multi-resistant strains prevents its eradication. ln 2016, the OMS launched new geais for global eradication of the disease (End TB), geais that, in Brazil, were disclosed through the \"National Planto End TB,\" from the Ministry of Health. ln arder to reach these geais, studies in search of new anti-mycobacterials that could lessen the treatment time and its adverse effects have a fundamental role. Molecular modeling and rational planning optimize the search for new potential drugs. Thus, QSAR models in line with computer-aided drug design (CADD) were used for the molecule proposition that became the synthesis target of this work. Two distinct proceedings were utilized to synthesize 1-H-2-aminoindole from the ortho-chloronitrobenzene. Simultaneously, four succinamic acids were prepared by the reaction of succinic anhydride with different amines. Posteriorly, each succinamic acid should be coupled with 1-H-2-aminoindole by way of coupling agents such as carbodiimides. The results obtained indicate that DCC in dichloromethane can be efficient for the synthesis of potential new drugs.

No description available.

Dans le but d'améliorer le rendement des cellules à colorant de type p (DSSC-p), ces travaux s'attachent à la synthèse et la caractérisation de matériaux semi-conducteurs de type p (SCs-p) sous forme de nanoparticules. En ce sens, des SCs-p répondant à un cahier des charges (bande de valence basse en énergie, grande surface spécifique, bon conducteur et bonne transparence) ont été étudiés. Dans ce cadre, une stratégie a été développée pour améliorer les propriétés de NiO (l'actuel matériau de référence) en optimisant sa nanostructuration, sa forte non-stœchiométrie en nickel et par son dopage à l'azote, paramètres tous favorables à la stabilisation de la valence mixte Ni3+/Ni2+, origine de la conductivité de type p. Cette longue étude a été initiée à partir d'un précurseur de nickel original nanostructuré Ni3O2(OH)4, à forte valence mixte Ni3+/Ni2+. La décomposition sous air et sous ammoniac de ce précurseur à basse température (250 °C) a permis de préparer Ni1-xO nanostructuré, fortement non-stœchiométrique (VNi = 25 %), de grande surface spécifique (240 m2.g-1) et dopé azote (NiO:N). De plus, deux matériaux non oxydes à structure delafossite, que sont les carbodiimides de nickel (NiNCN) et de manganèse (MnNCN) ont été préparés et caractérisés comme de nouveaux semi-conducteurs de type p, permettant de monter la première DSSC-p à base de NiNCN. / To improve the performances of p-Dye Sensitized Solar Cell (p-DSSC), this thesis work focuses on the synthesis and the characterization of p-type semiconductors (p-SCs) nanomaterials. These p-SCs with some specifications (low energy valence band, high specific surface area, high conductivity and transparency) were thoroughly studied. In this context, a strategy was developed to improve the NiO nanoparticles properties (commonly used as a reference) with higher nickel non-stoichiometry and nitrogen doping to promote the stabilization of the Ni3+/Ni2+ mixed valence (origin of the p-typness). This study was initiated with a nanostructured mixed valent Ni3O2(OH)4 precursor. Its thermal decomposition in air and ammonia at low temperature (250 °C) allows the formation of nanostructured Ni1-xO with a large amount of Ni vacancies (VNi = 25 %), a high specific surface area (240 m2.g-1) and a nitrogen doping (NiO:N). Moreover, two non-oxides materials with delafossite structure type, namely - nickel carbodiimide (NiNCN) and manganese carbodiimide (MnNCN) - were prepared and characterized as new p-type semiconductors. Thus, the first p-DSSC with NiNCN material was built with success.