A variety of organometallic-fused heterocycles and acene quinones were prepared and characterized. This work was divided into three parts: first, the synthesis of 5,5-fused heterocyclic complexes of tricarbonylmanganese and (1’,2’,3’,4’,5’-pentamethylcyclopentadienyl)ruthenium; second, the synthesis of 1,2-diacylcyclopentadienyl p-cymene complexes of ruthenium(II); and third, synthesis of cyclopentadienyl-fused polyacenequinone complexes of ruthenium, iron and manganese. The first examples of the convenient, versatile and symmetric cyclopentadienyl-fused heterocycle complexes of (1’,2’,3’,4’,5’-pentamethylcyclopentadienyl)ruthenium(II) and tricarbonylmanganese(I) were synthesized starting from (1,2-dicarbophenoxycyclopentadienyl)sodium. The sodium salt was transmetalated using [MnBr(CO)5] and 1/4 [Ru(μ3-Cl)(Cp*)]4 to give [Mn(CO)3{η5-C5H3(CO2Ph)2-1,2}] and [Ru{η5-C5H3(CO2Ph)2-1,2}(Cp*)]. The diester complexes were saponified under basic conditions to obtain the corresponding dicarboxylic acids. The dicarboxylic acids were used to synthesize unique cyclopentadienylmetal complexes including diacyl chlorides, anhydrides, thioanhydrides and p-tolyl imides of ruthenium and manganese. Similarly, a series of 1,2-diacylcyclopentadienyl-p-cymene cationic complexes of ruthenium were synthesized using thallium salt of 2-acyl-6-hydroxyfulvene and [Ru(η6-p-cymene)(μ-Cl)Cl]2 in a 2:1 ratio with an intension of converting them into heterocycle-fused cationic sandwich complexes. However, our attempts of ring closing on 1,4-diketons with sulfur or selenium were unsuccessful. A methodology involving the synthesis of metallocene-fused quinone complexes was employed starting from pentamethylruthenocene-1,2-dicarboxylic acids. The diacyl chloride was prepared in situ from the dicarboxylic acids and used for Friedel-Crafts acylation. We observed single-step room-temperature diacylation of aromatics, including benzene, o-xylene, toluene, 1,4-dimethoxybenzene and ferrocene with pentamethylruthenocene-1,2-diacyl chloride to obtain the corresponding quinone complexes. Similarly, we synthesized mononuclear and binuclear γ-quinones by aldol condensation of 1,2-diformylcyclopentadienylmetal complexes with cyclohexane-1,4-dione or 1,4-dihydroxyarenes. The third methodology involves the Friedel-Crafts acylation of ferrocene with 2-carbomethoxyaroyl chlorides followed by saponification, carbonyl reduction, and ring closing by second Friedel-Crafts acylation to give Ferrocene-capped anthrone-like tricyclic and tetracyclic ketones. The oxidation of the ketones gave [3,4-c]-fused α-quinone complexes of iron. The oxidative and reductive coupling, enolization and C-alkylation of the anthrone complex were studied. Solvolysis of α-carbinol gave α-ferrocenylcarbenium salt, which underwent dimerization on treatment with non-nucleophilic base. We were successful to trap the in situ generated trimethylsilylenol ether of ferrocene-anthrone using dienophiles like N-phenylmaleimide or dimethylacetylenedicarboxylate under Diels-Alder conditions.

N-Acylphosphatidylethanoiamine (NAPE) is synthesized in the microsomes of cotton seedlings by a mechanism that is possibly unique to plants, the ATP-, Ca2+-, and CoA-independent acylation ofphosphatidylethanolamine (PE) with unesterified free fatty acids (FFAs), catalyzed by NAPE synthase. A photoreactive free fatty acid analogue, 12-[(4- azidosalicyl)amino]dodecanoic acid (ASD), and its 125I-labeled derivative acted as substrates for the NAPE synthase enzyme.

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Les céramides sont des lipides de la classe des sphingolipides issus de la N-acylation d’une base sphingoide par un acide gras. Ces lipides et leurs analogues suscitent un grand intérêt comme composants actifs dans les industries pharmaceutique et cosmétique. Parmi les biocatalyseurs capables de réaliser la synthèse de ce type de lipide, la lipase B de Candida antarctica semble être l’enzyme la plus adaptée à la production de « pseudo-céramides » à partir d’amino-polyols. Dans ce contexte, nous avons abordé l’étude de l’acylation de composés de type « amino-alcool »catalysée par la lipase B de Candida antarctica, en gardant à l'esprit une approche fondamentale afin d’élargir les connaissances actuelles sur ce sujet. La première partie de notre travail a ainsi traité de l’étude cinétique de l’acylation de composés monofonctionnels afin de déterminer les mécanismes réactionnels et l’énantio sélectivité de la lipase B de Candida antarctica pour les réactions de N-acylation et de O-acylation. Les parties suivantes de notre travail ont porté sur une étude structure-réactivité du substrat accepteur d’acyle et sur l’étude de l’influence du solvant utilisé (solvant organique ou liquide ionique) afin de déterminer les facteurs clés influençant la chimio sélectivité et la régio sélectivité de la lipase B de Candida antarctica lors de l’acylation de composés multifonctionnels de type « amino-alcool ». Finalement, à partir des connaissances acquises dans les différentes parties, nous avons développé et optimisé un procédé de synthèse enzymatique de « pseudo-céramides » (O,N-diacyl aminopropanediols) mis en oeuvre en réacteur continu à « lit fixe ». / Ceramides are lipids from the sphingolipide class derived from the N-acylation of a sphingoid base from a fatty acid. These lipids and their analogs are compounds of interest used as active components in pharmaceutical and cosmetic industries. Among biocatalysts able to synthesize this type of lipids, Candida antarctica lipase B appears to be the most appropriate enzyme for the production of "pseudo-ceramides" derived from amino-polyols. In this context, we have studied the acylation of amino-alcohol-like compounds catalyzed by Candida antarctica lipase B, keeping inmind a fundamental approach to expand the current knowledge on this subject. The first part of our work aimed to determine the reaction mechanisms and the enantio selectivity exhibited by Candida antarctica lipase B during O-acylation and N-acylation reactions, by conducting a kinetic study of mono functional compound acylation. In the following parts of our work, we performed a structurere activity study of the acyl acceptor substrate and evaluated the effect of the solvent used (organic solvent or ionic liquid) to determine the key factors influencing the chemo selectivity and the regio selectivity of the Candida antarctica lipase B-catalyzed acylation of polyfunctional amino alcohol compounds. Finally, starting from the knowledge acquired in the previous parts, we have developed and optimized an enzymatic process of “pseudo-ceramide” (O,N-diacylaminopropanediol) synthesis performed in a continuous packed-bed reactor.

Hemolysin toxin produced and secreted by pathogenic Escherichia coli is one of a family of cytolytic, structurally homologous protein toxins known as RTX (repeats in toxin) toxins. RTX toxins are products of a gene cluster, CABD . The A gene product, nontoxic hemolysin (proHlyA) is made toxic by post-translational fatty acylation of two internal lysine residues. HlyC, C gene product, is essential for acylation, and acyl-acyl carrier protein (ACP) is the acyl donor. HlyB and HlyD are involved in secretion of the toxin. HlyC was thought to serve as an internal protein acyltransferase and remained uncharacterized until now. ProHlyA and HlyC were separately subcloned, expressed, and purified, and acyl-ACPs with diverse radioactive acyl groups were synthesized. With these proteins, the conversion of proHlyA to HlyA by acyltransfer was assayed. Acyl-ACP was the obligate acyl donor. Acyltransfer was catalyzed by HlyC monomer, and an acyl-enzyme intermediate was detected and shown to catalyze the reverse reaction. The reaction mechanism was examined by steady state kinetics, and the nature of inhibitions by reaction products was determined. The kinetic mechanism of the internal protein acylation was compatible with an uni uni iso uni uni ping pong with isomerization of the F form of the enzyme. Clues to the chemical mechanism for the acyltransferase were elucidated by both chemical modification studies and site directed mutagenesis of the enzyme. Chemical modification experiments ruled out any critical cysteines, serines, and lysine residues, but suggested a role for histidine(s) and tyrosine(s) in acyltransferase function. In order to examine the function of specific residues and possibly corroborate the chemical findings, site directed mutagenesis studies of the acyltransferase were employed. Seventeen residues that were conserved among 13 different RTX toxin acyltransferases were individually mutated, and the respective HlyCs expressed, and characterized. Residues that were critical for acyltransferase function included Gly 11, His 23, Tyr 70, and Gly 85. As with chemical modification data, mutagenesis ruled out any conserved, essential, cysteines or serines critical for HlyC acyltransferase activity.

Thesis (M.Sc.)--Memorial University of Newfoundland, 2005. / Bibliography: leaves 97-99.

Thesis (Ph.D.)--McMaster University (Canada), 1994. / Source: Dissertation Abstracts International, Volume: 56-08, Section: B, page: 4324. Adviser: P. Harrison.

Thesis (M.S.)--Mississippi State University. Department of Chemistry. / Title from title screen. Includes bibliographical references.

Orientador: Rosiane Lopes da Cunha / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia de Alimentos / Made available in DSpace on 2018-08-18T08:17:47Z (GMT). No. of bitstreams: 1 Reis_Cathiados_M.pdf: 2669539 bytes, checksum: 364324f89741f00357d22a38d35ee9ee (MD5) Previous issue date: 2011 / Resumo: A gelatina é uma proteína de alto interesse e valor comercial, no entanto seu uso como agente emulsificante ainda é bastante restrito devido à limitações tecnológicas. O objetivo geral deste trabalho foi investigar as alterações nas propriedades físicas, químicas e funcionais da gelatina de origem bovina quando submetida à modificação química através da reação de acilação com um cloreto de ácido graxo, bem como avaliar seu desempenho em aplicações com finalidade tecnológica de emulsificação. Para a definição das condições ótimas de reação de acilação (pH de reação e concentração do reagente), foram avaliados o grau de acilação (GA), a atividade (AE) e estabilidade emulsificante (ES), a força de gel (Bloom) e a viscosidade. As gelatinas aciladas obtidas foram também caracterizadas quanto aos teores de proteína, cinzas, umidade, cloretos, distribuição de peso molecular, ponto isoelétrico e espectroscopia de infravermelho. As emulsões (20% óleo) produzidas utilizando as gelatinas aciladas foram avaliadas através de medidas de separação visual de fases e determinação de tamanho de gota por microscopia ótica. Os resultados mostraram que a reação de acilação apenas tornou-se efetiva quando realizada em pH extremamente alcalino (pH 11,0), porém a força de gel e a viscosidade diminuíram nestas condições. As gelatinas aciladas com maior força de gel e viscosidade mostraram maior efeito na estabilização das emulsões do que o grau de acilação. Como conseqüência, as gelatinas ¿controle¿ apresentaram melhor atuação na estabilização das emulsões. Não foram observadas diferenças significativas na distribuição de ponto isoelétrico das gelatinas e nos espectros de infravermelho obtidos. No entanto, as gelatinas aciladas em pHs mais altos (pH 10,6 e 11,0) apresentaram aumento da massa molecular média quando comparadas as gelatinas ¿controle¿ devido a introdução do grupo acila na cadeia de gelatina / Abstract: Gelatin is a protein widely used in food industry. However, its use as an emulsifier agent is still restricted due to technological limitations. The objective of this work was to investigate the alterations at physical, chemical and functional properties of bovine gelatin after it has been subjected to a chemical modification through the acylation with a fatty acid chloride. In addition, the behavior of this acylated gelatin as emulsifier was evaluated. The acylation degree (AD), the emulsifying activity (EA) and stability (ES), the gel strength (or Bloom) and the viscosity of the modified gelatins were evaluated to define the more adequate conditions of the acylation reaction (pH and reactive concentration). The acylated gelatins were characterized regarding to protein, ash, moisture, chloride content, molecular weight distribution, isoelectric point distribution and infrared spectroscopy. O/W emulsions (20% oil) stabilized with acylated gelatins were evaluated through visual phase separation measurements and determination of drop size using optical microscopy. The results showed that the acylation reaction was effective only at very high pH (around 11.0). However, the gel strength and viscosity decreased at higher pH of reaction. Acylated gelatins with higher gel strength and viscosity showed more pronounced effect on emulsions stability than the acylation degree. As a consequence, the ¿control¿ gelatins presented better emulsion stability than acylated ones. It was not observed significant differences at isoelectric point distribution and infrared spectrum obtained for the acylated gelatins. However, acylated gelatins at higher pH (pH 10.6 and 11.0) showed an increase of the mean molecular mass when compared to the ¿control¿ gelatins due to the introduction of acyl groups to the gelatin chain / Mestrado / Engenharia de Alimentos / Mestre em Engenharia de Alimentos

京都大学 / 0048 / 新制・課程博士 / 博士(薬科学) / 甲第19660号 / 薬科博第48号 / 新制||薬科||6(附属図書館) / 32696 / 京都大学大学院薬学研究科薬科学専攻 / (主査)教授 川端 猛夫, 教授 高須 清誠, 教授 竹本 佳司 / 学位規則第4条第1項該当 / Doctor of Pharmaceutical Sciences / Kyoto University / DFAM