Dissertação composta por 02 artigos. / CNPq; Capes / O leite é uma das principais fontes de nutrientes da dieta humana e é um alimento que acompanha o ser humano durante toda a vida, tanto como leite de consumo como através de seus derivados. Entretanto, são inúmeras as formas e os tipos de contaminação que acometem o leite, destacando-se, dentre os contaminantes de ordem química, as aflatoxinas. Dentre os métodos de análise de aflatoxinas em leite e derivados, destaca-se a Cromatografia Líquida de Alta Eficiência (CLAE), principalmente devido a sua versatilidade, rapidez e acuracidade das medidas quantitativas. Entretanto, trata-se de um sistema complexo em que as propriedades dos constituintes da fase móvel são afetadas por mudanças nas condições de processo nas quais são realizados os experimentos. Normalmente as condições de análise por CLAE são determinadas empiricamente, pelo método “tentativa e erro” em que inúmeras tentativas são realizadas sem um estudo mais detalhado do sistema. Diante disso, a primeira etapa deste estudo objetivou a otimização de multirrespostas em CLAE, por meio da seleção das condições ótimas como a composição da fase móvel, sua vazão no sistema cromatográfico e a temperatura da coluna, a fim de identificar, separar e quantificar simultaneamente a aflatoxina M1 (AFM1) e a aflatoxina B1 (AFB1). Para tanto, realizou-se planejamento experimental de misturas para três componentes com restrições combinado com um planejamento fatorial 22 para as variáveis de processo (temperatura da coluna e vazão). Após a definição dos modelos para as variáveis dependentes, foi realizada busca das condições ótimas usando o método simplex sequencial e as funções de desejabilidade de Derringer e Suich. As variáveis avaliadas foram: composição da fase móvel (acetonitrila, metanol e solução aquosa de ácido acético 1%), vazão da fase móvel e temperatura da coluna. Os parâmetros cromatográficos obtidos como respostas foram: tempo e fator de retenção para ambas as aflatoxinas, fator de separação, resolução da coluna e altura dos picos. Após a validação do planejamento, foi realizada a validação analítica do método otimizado através das figuras analíticas de mérito: linearidade, precisão, exatidão e limites de detecção e quantificação. O planejamento realizado foi capaz de produzir modelos confiáveis que possibilitaram a estimativa das melhores condições atendendo aos múltiplos objetivos. Na validação analítica do método cromatográfico, os parâmetros analíticos avaliados ficaram dentro dos intervalos de confiança, podendo o método ser considerado exato e preciso, apresentando limites de quantificação de 0,3 e 0,5 μg L-1 para AFM1 e AFB1, respectivamente e linearidade com R2 > 0,99 para ambas as aflatoxinas. A segunda etapa do estudo objetivou a avaliação da interação entre as AFM1 e AFB1 com proteínas lácteas, tendo em vista que estudos demonstram que aquelas, especialmente a AFM1, localizam-se predominantemente nas frações proteicas. Entretanto, esses estudos não avaliaram a interação entre aflatoxinas e as proteínas do leite, mas apenas baseiam-se na sua quantificação nas frações proteicas do leite. Portanto, buscou-se por meio deste estudo avaliar a possível interação entre as AFM1 e AFB1 com as frações proteicas do leite. Análises por Espectroscopia na região de infravermelho com transformada de Fourier (FTIR) foram realizadas para avaliação de possíveis modificações na estrutura secundária das proteínas lácteas quando fortificadas com as aflatoxinas e Calorimetria Exploratória Diferencial (DSC). Para tanto, preliminarmente foram avaliados os espectros obtidos com padrões de caseína e β-lactoglobulina em solução tampão fosfato-salino (PBS) e em solução modelo, assim como no leite propriamente dito, integral e desnatado. Na segunda etapa, regiões espectrais específicas foram avaliadas por meio de técnicas de deconvolução e curve-fitting. Os resultados indicam que a solução PBS foi mais adequada para o estudo da interação entre as AFB1 e AFM1 e proteínas lácteas avaliadas, β-lactoglobulina e caseína. Foram observadas alterações nas estruturas secundárias e essas sugerem que, embora possivelmente ocorram interações de caráter hidrofílico entre β-lactoglobulina e as aflatoxinas (especialmente com AFM1), ocorram também interações de caráter hidrofóbico (especialmente de AFB1) com os pacotes hidrofóbicos da β-lactoglobulina. Já com a caseína, as alterações promovidas nas estruturas secundárias proteicas foram mais discretas, porém deslocamentos de picos foram observados indicando alterações estruturais da proteína, especialmente na presença de AFB1, o que sugere que ocorram interações químicas entre os componentes avaliados. As alterações espectrais, mais evidentes com a fração β-lactoglobulina, do que com a fração caseína sugerem que, embora a quantificação de aflatoxinas seja comumente superior na fração caseína, não se pode afirmar que por esse motivo ocorram interações mais tangíveis entre aflatoxinas e caseína do que entre aflatoxinas e β-lactoglobulina. Possivelmente a quantificação em maior percentual de aflatoxinas na fração caseína é atribuída ao fato dessa proteína encontrar-se, no leite, em percentual superior às proteínas do soro. Outra hipótese levantada pelo estudo é a possibilidade das aflatoxinas avaliadas encontrarem-se “mascaradas” por estarem conjugadas com a β-lactoglobulina e não sendo, portanto, detectadas pelos métodos analíticos convencionais ocasionando sua subestimação nessa fração. / Milk is one of the main sources of nutrients in the human diet and is a food that accompanies the human being throughout life, both as drinking milk as through its derivatives. However, there are countless forms and types of contamination that affect milk, especially among the contaminants of chemical order, aflatoxins. Among the methods of analysis of aflatoxins in milk and dairy products, the High Performance Liquid Chromatography (HPLC) stands out mainly due to its versatility, speed and accuracy of quantitative measurements. However, it is a complex system in which the properties of the constituents of the mobile phase are affected by changes in process conditions under which the experiments are performed. Typically the HPLC analysis conditions are determined empirically, using the "trial and error" in which numerous attempts are made without a more detailed study of the system. Therefore, the first step of this aimed to optimize multiresponses in HPLC, by selecting the optimal conditions as the mobile phase composition, its flow into the chromatographic system and the column temperature in order to identify, separate and quantify aflatoxin M1 (AFM1) and aflatoxin B1 (AFB1) simultaneously. Therefore, it was carried out experimental a mixture design for three components with restrictions combined with a 22 factorial design to the process variables (flow and column temperature). After defining the models for the dependent variables, a search of the optimum conditions was made using the sequential simplex method and the Derringer and Suich desirability functions. The variables evaluated were: mobile phase composition (acetonitrile, methanol and aqueous solution of acetic acid 1%), the mobile phase flow rate and column temperature. The chromatographic parameters obtained as responses were time and factor of retention for both aflatoxins, separation factor, column resolution and height of the peaks. After the design validation, analytical validation was performed through the analytical figures of merit: linearity, precision, accuracy and limits of detection and quantification. The experimental design carried out was able to produce reliable models that allowed better conditions estimation regarding multiple objectives. In the analytical validation of the chromatographic method, the analytical parameters evaluated were within the confidence interval, the method can be considered accurate and precise showing quantitation limits of 0.3 and 0.5 μg L-1 for AFB1 and AFM1, respectively, and linearity with R2> 0.99 for both aflatoxins. The second stage of the study aimed to evaluate the interaction between the AFB1 and AFM1 with dairy proteins, considering that studies show that those, especially AFM1, are located predominantly in the protein fractions. However, these studies did not evaluate the possibility of interaction between aflatoxins and dairy proteins, but only based on its quantification in the dairy protein fractions. Therefore, we sought through this study to evaluate a possible interaction between AFM1 and AFB1 with dairy protein fractions. Analyzes were performed by Fourier transformation infrared spectroscopy (FTIR) to assess possible changes in the secondary structure of dairy proteins when spiked with aflatoxins and Differential Scanning Calorimetry (DSC). For this purpose, preliminarily the spectra obtained were evaluated with standard casein and β-lactoglobulin in phosphate buffer saline solution (PBS) and a bovine milk model solution as well as in actual milk, whole and skim. In the second step, specific spectra bands were assessed through deconvolution and curve-fitting techniques. The results show that PBS was more suitable for the interaction study between aflatoxins B1 and M1 and the dairy proteins evaluated, β-lactoglobulin and casein. Changes in secondary structures suggest that although possibly occurring interactions with hydrophilic characters between β-lactoglobulin and aflatoxins were observed (especially with AFM1) also occur interactions with hydrophobic character (especially AFB1) with the hydrophobic β-lactoglobulin packages. Already with the casein, the changes introduced in protein secondary structure were more discreet but peak shifts were observed indicating structural changes of the protein, especially in the presence of AFB1, which suggests that chemical interactions occur between the components evaluated. The spectral changes, more evident with the β-lactoglobulin fraction than the casein fraction, suggests that although the quantification of aflatoxins is commonly higher in the casein fraction, it’s not possible to ensure that for this reason occur more tangible interactions between aflatoxins and casein than between aflatoxins and whey proteins (β-lactoglobulin). The greater quantify percentage of aflatoxins in the casein fraction, apparently, is attributed to the fact that this protein is found, in milk, in superior percentage to the whey proteins. Another hypothesis is the possibility of the aflatoxins evaluated are "masked" by being combined with β-lactoglobulin and not, therefore, being detected by conventional analytical methods leading to their underestimation in this fraction. / 5000

Orientador: Célia Maria Landi Franco / Banca: Beatriz Rosana Cordenunsi / Banca: Silene Bruder Silveira Sarmento / Banca: Neuza Jorge / Banca: José Francisco Lopes Filho / Resumo: O efeito da β-ciclodextrina (βCD) na formação de complexos amilose-lipídios e/ou amilopectina-lipídios usando monoestearato de glicerol (GMS) (1, 2 e 3% m/m) e amidos de trigo, milho normal, milho ceroso e milho com alto teor de amilose foram estudados físico-química e estruturalmente na presença ou ausência de β-ciclodextrina (βCD) (3% m/m). Os amidos de trigo e milho normal se caracterizaram por apresentarem teores de amilose semelhantes (~ 25%) e padrão de raios-X tipo A. O amido de milho com alto teor de amilose (49,8%) apresentou padrão cristalino tipo B, enquanto o amido de milho ceroso, com padrão tipo A, teve 1,1% de amilose. O maior teor de lipídios (0,75%) e fósforo (0,05%) no amido de trigo contribuiu para sua menor temperatura de gelatinização. A adição de βCD nos amidos nativos interferiu na formação dos complexos amilose-lipídios presentes naturalmente nos amidos, de forma mais intensa no amido de trigo devido principalmente ao seu maior teor e tipo de lipídios. A adição de GMS reduziu a viscosidade de quebra e setback nos amidos de trigo, milho normal e milho ceroso devido à dificuldade de retrogradação das moléculas de amilose e/ou amilopectina complexadas. Após a adição da βCD, o ΔHcx aumentou para os amidos de trigo, milho normal e milho com alto teor de amilose, sugerindo o rompimento do complexo amilose-GMS pela βCD e associação entre βCD e GMS. Os complexos produzidos dos amidos com GMS (1, 2 e 3%) mostraram estruturas facetadas típicas de cristais quando observados em MEV e AFM, padrão cristalino tipo V e picos endotérmicos de dissociação entre a C, o que os classificou como complexos com polimorfismo IIb. Os resultados mostraram que 1% de GMS foi suficiente para complexar com as moléculas de amilose e/ou amilopectina disponíveis para complexação nos amidos de trigo, milho normal e milho ceroso, enquanto que no amido de milho com alto teor de amilose, concentrações abaixo ... / Abstract: Effect of β-cyclodextrin (βCD) in the formation of amylose-lipid and / or amylopectin-lipids complexes using glycerol monostearate (GMS) (1, 2, 3% w/w), and wheat, normal corn, waxy corn and high amylose starches were physicochemically and structurally evaluated in the presence or absence of β-cyclodextrin (βCD) (3% w/w). Normal corn and wheat starches were characterized by similar amylose content (~ 25%) and A-type X-ray pattern. High amylose corn starch (49.8%) presented the B-type crystalline pattern, whereas the waxy corn starch with A-type crystalline pattern had 1.1% of amylose. The higher lipid (0.75%) and phosphorus (0.05%) contents in wheat starch contributed to its lower gelatinization temperature. Addition of βCD in native starches suggested that this oligosaccharide interfered in the formation of amylose-lipid complexes naturally present in starches, more intensely in the wheat starch mainly due to their higher content and type of lipids. Addition of GMS reduced breakdown and setback in wheat, normal corn and waxy corn starches due to the retrogradation complications of the amylose and/or complexed amylopectin molecules. After the βCD addition, there was an increase of ΔHcx for wheat, normal corn, and high amylose corn starches, suggesting the amylose-GMS complex disruption by βCD and a possible association between βCD and GMS. The produced complexes of starches with GMS (1, 2 and 3%) disclosed faceted structures typical of crystals when observed by SEM and AFM, V-type crystalline pattern and endothermic peaks of dissociation between115 to 120 ° C, which classify them as IIb polymorphism. The results suggested that 1% of GMS was enough to complex with amylose and / or amylopectin molecules available for complexing in the wheat, normal corn, and waxy corn starches, whereas in the high amylose corn starch, concentrations below 3% GMS were not enough to saturate and complex all available amylose. The resistant starch ... / Doutor

Orientador: Raul Cesar Evangelista / Coorientador: Beatriz Stringhetti Ferreira Cury / Banca: Marco Vinícius Chaud / Banca: Ana Dóris de Castro / Resumo: As matrizes hidrofílicas destacam-se como sistemas sólidos para a liberação controlada de fármacos destinados à via oral de administração de medicamentos, devido à relativa facilidade de processamento, possibilidade de incorporação de elevadas doses de fármaco e obtenção de perfis de liberação reprodutíveis. O amido resistente tipo 3 (AR3) e a pectina (P) são polímeros resistentes à ação das enzimas digestivas, sendo seletivamente degradados pela microbiota colônica, o que os tornam potenciais candidatos para a obtenção de sistemas de liberação controlada de fármacos. Nesse trabalho, o AR3 foi obtido através da retrogradação do amido por dois métodos diferentes: Método 1 (M1) - armazenamento sob resfriamento, por 8 dias (4°C) e Método 2 (M2) - armazenamento por 16 dias em ciclos alternados de temperatura (4°C e 30°C, 2 dias em cada temperatura). As propriedades físico-químicas dos materiais retrogradados (cristalinidade, comportamento térmico, intumescimento e porosidade) foram avaliadas e o conjunto de resultados evidenciou modificações estruturais promovidas pelo processo de retrogradação. As propriedades micromeríticas desses materiais (distribuição de tamanho, forma, densidade e fluxo) foram também avaliadas e mostraram-se favoráveis ao processo de compressão. O desempenho dos materiais como excipiente de comprimidos destinados à liberação controlada de fármacos foi avaliado através do ensaio de liberação in vitro do diclofenaco de sódio, em meios com diferentes valores de pH (1,2 e 7,4). A influência da incorporação da pectina aos sistemas no controle das taxas de liberação do fármaco foi avaliada. Os perfis de liberação obtidos demonstraram um efetivo controle das taxas de liberação do fármaco em meio ácido, visto que, em 120 min, os comprimidos obtidos por M1 ou M2 (20 e 40%) liberaram de 42% a 49,49% do fármaco, enquanto os comprimidos obtidos com APR e APM liberaram.. / Abstract: Hydrophilic matrices represent important solid systems for controlled drug delivery intended to oral administration of drugs, because of the relative ease of processing, possibility of incorporating large amounts of drug, and obtaining reproducible release profiles. Resistant starch type 3 (AR3) and pectin (P) are polymers resistant to the action of digestive enzymes and are selectively degraded by colonic microbiota, making them potential candidates for drug delivery systems. In this work, retrograded starch (AR3) was prepared by starch retrogradation by two different methods: Method 1 (M1) - cooling for 8 days at 4° C and Method 2 (M2) - storage for 16 days in alternating temperature cycles (4° C and 30° C, 2 days at each temperature). The physico-chemical properties of the retrograded materials (crystallinity, thermal behavior, swelling and porosity) were evaluated and the results showed structural changes caused by the retrogradation process. Micromeritic properties of these materials (size distribution, shape, density and flow) were also evaluated and showed to be suitable to the compression process. The performance of the materials as tablet excipient intended for controlled drug release was evaluated through the in vitro release of sodium diclofenac in media with different pH values (1.2 and 7.4). The influence of the incorporation of pectin to the systems in controlling the drug release rates was evaluated. The release profiles of all obtained tablets demonstrated effective control of drug release in acid media since tablets prepared with M1 or M2 released from 42 to 49% of drug. Tablets prepared with APR and APM released about 34.5% and 22.8%, respectively. In enteric media, the tablets obtained by M1 or M2 (20 and 40%) showed an increased rate of drug release, so that the t80% occurred at approximately 60 min, while for the tablets obtained with AA this time was of approximately 120 min. The tablets obtained with APR and APM ... / Mestre

A química de carboidratos têm sido um importante link entre a síntese orgânica, a biologia e a química medicinal devido ao papel fundamental que açúcares apresentam na glicobiologia. Neste contexto, a ligação amida glicosídica é uma importante conexão encontrada na natureza, sendo uma das formas de ligar um núcleo de carboidrato a outras biomoléculas e produtos naturais, como glicopeptídeos e N-glicosil amidas. Dessa forma, o desenvolvimento de métodos sintéticos para a introdução de núcleos de carboidratos em diferentes estruturas é fundamental. Tendo em vista o interesse do nosso grupo de pesquisa em desenvolver novas estratégias utilizando a química de selênio na funcionalização de derivados de carboidratos, o presente projeto descreve uma metodologia de síntese de N-glicosil amidas e de glicoconjugação via formação de ligação amida, envolvendo a reação entre selenocarboxilatos, gerados in situ, com azidas glicosídicas. Foi possível sintetizar com sucesso uma série de derivados de carboidratos, para uma variedade de substratos que incluíram: N-glicosil amidas furanosídicas (20 exemplos), piranosídicas (13 exemplos) e também N-glicoconjugados graxos (10 exemplos). A metodologia foi baseada na geração in situ de selenocarboxilatos de lítio, a partir de Se0/ LiEt3BH e derivados de ácidos carboxílicos, e suas reações com azidas derivadas de açúcares. Um aspecto importante deste protocolo é que a reação se inicia com selênio elementar e apresenta como subprodutos N2 e Se0. O isolamento e manipulação de espécies intermediárias reativas de selênio são evitadas durante o curso reacional, conferindo ao selenocarboxilato o status de reagente traceless. / Carbohydrate chemistry has been an important link between organic synthesis, biology and medicinal chemistry due to the fundamental roles that sugars play in glycobiology. In this context, the glycosyl amide linkage is an important connection found in nature, since it is one of the ways in which a sugar unit can be found attached to other biomolecules and natural products, such as N-glycosyl amides and glycopeptides that are known for possessing a wide range of bioactivities. Therefore, the development of synthetic methods for the introduction of sugar moieties into various different scaffolds is of paramount importance. In connection with our interest on the development of new strategies using selenium chemistry for the functionalization of carbohydrate derivatives, we describe herein an efficient synthesis of glycosyl amides and glycoconjugation methodology via amide bond-formation, enabled by the reaction of in situ generated selenocarboxylates with glycosyl azides. Carbohydrate-derived amides were successfully prepared in good yields for a broad range of substrates, including: furanosyl (20 examples), pyranosyl (13 examples) N-glycosil amides derivatives and also fatty acids glycoconjugates (10 examples). The methodology relied in the in situ generation of lithium selenocarboxylates, from Se/LiEt3BH and acyl chlorides or carboxylic acids and their reaction with sugar azides. A key aspect of the present protocol is that we start from elemental selenium and as by-products we have harmless gaseous nitrogen and elemental selenium. Isolation and handling of all reactive and sensitive seleniumcontaining intermediates is avoided, therefore assigning to the selenocarboxylate the status of a traceless reagent.

Dans cette thèse, la synthèse, la caractérisation et les applications catalytiques préliminaires des nanoparticules mono- et bi-métalliques à base de rhénium sont présentées. Le Rhénium a été choisi compte tenu de la connaissance de sa contribution positive en termes d'activité catalytique et la sélectivité lors de l'hydrogénation des groupes fonctionnels difficiles. Les nanoparticules mono-métalliques de rhénium ont été préparées par décomposition du précurseur [Re2(C3H5)4]. Les nanoparticules bimétalliques ont été synthétisés par les co-décompositions ou deux étapes décomposition de deux complexes différents de rhénium, à savoir [Re2(CO)10] et [Re2(C3H5)4] avec d'autres complexes organométalliques tels que [Ru(COD)(COT)], [Ru(Me-allyl)2(COD)], [Pt(CH3)2(COD)] et [Pt(C7H10)3]. En choisissant la nature des complexes organométalliques et les conditions de réaction, des nanoparticules bi-métalliques à base de rhénium présentant des morphologies différentes peuvent être préparées quantitativement. La synthèse a été effectuée en solution sous pression de dihydrogène (3 bars) et en présence soit d'une polymère (polyvinylpyrrolidone), ou un ligand faiblement coordinant (hexadécylamine) comme des agents stabilisant. La caractérisation précise des nanoparticules ainsi obtenues a été réalisée en utilisant une combinaison de l'état de l'art des techniques de (WAXS, EXAFS, MET, HR-MET, METS-EDX, METS-HAADF, AE). Les études de réactivité de surface (réactions hydrogénation de norbornène, oxydation et adsorption CO) ont également été réalisées et suivies par des techniques spectroscopiques (RMN, FT-IR) pour déterminer leur état de surface et appréhender leur intérêt pour la catalyse. Par ce moyen, des informations utiles ont été obtenues sur leur chimie de surface, comme suit: 1) hydrures sont présents sur la surface métallique et sont très fortement coordonnés à la surface de rhénium en accord avec la chimie moléculaire de rhénium; 2) CO peut remplacer les hydrures et est également fortement coordonné à la surface, mais peut être substitué, oxydée ou dissocié. Ces réactions sont plus faciles sur des nanoparticules bi-métalliques à base de Re de type alliage. 3) Les NPs de rhénium pur et les alliages bimétalliques nanoparticules de ruthénium et rhénium affiche un état de base zéro et une coquille d'oxyde alors que les nanoparticules bimétalliques de type cœur-coquille ont une structure amorphe. L'originalité de ce travail réside sur le développement d'une approche systématique pour la préparation de nanoparticules à base de rhénium pour la première fois dans l'équipe et dans la littérature, en appliquant l'approche organométallique largement connu dans le groupe pour d'autres systèmes métalliques. Cette méthode est bien connu comme un moyen efficace d'obtenir des nanostructures bien contrôlées avec des surfaces propres ce qui est important principalement en catalyse. / In this PhD thesis, the synthesis, characterization and preliminary catalytic application of rhenium based mono- and bi-metallic nanoparticles are reported. Rhenium has been chosen as a primary metal given the knowledge of its positive contribution in terms of catalytic activity and selectivity in the hydrogenation of difficult functional groups. Mono-metallic rhenium nanoparticles were prepared by decomposition of [Re2(C3H5)4]. Rhenium-based bimetallic nanoparticles were synthesized by co-decompositions or two-step decomposition of two different rhenium complexes, namely [Re2(CO)10] and [Re2(C3H5)4], with other organometallic complexes such as [Ru(COD)(COT)], [Ru(Me-Allyl)2(COD)], [Pt(CH3)2(COD)] and [Pt(C7H10)3]. By tuning the nature of organometallic complexes and the reaction conditions, rhenium-based bimetallic nanoparticles displaying different morphologies could be quantitatively prepared. The synthesis was carried out in solution under mild pressure of dihydrogen (3 bar) and in the presence of either a polymer (polyvinylpyrolidone) or a weakly coordinating ligand (hexadecylamine) as stabilizing agents. The precise characterization of the so-obtained nanoparticles was performed by using a combination of state-of-the art techniques (WAXS, EXAFS, TEM, HRTEM, STEM-EDX, STEM-HAADF, EA). Surface reactivity studies (norbornene hydrogenation, oxidation and CO adsorption reactions) were also carried out and followed by spectroscopic techniques (NMR, FT-IR) to determine their surface state and apprehend better their interest in catalysis. By this way, useful information could be obtained on their surface chemistry, as following: 1) Hydrides are present on the metallic surface and are very strongly coordinated to rhenium in agreement with rhenium molecular chemistry; 2) CO can substitute hydrides and is also strongly coordinated to the surface of Re but can react further to be substituted, oxidized or dissociated, where the latter is easier on alloy type Re-based bimetallic nanoparticles. 3) Oxidation of pure rhenium and alloy bimetallic ruthenium-rhenium nanoparticles display a zero state core and an oxide shell while core-shell type bimetallic nanoparticles result in amorphous structure. The originality of this work lies on the development of a systematic approach for the preparation of rhenium-based nanoparticles for the first time in the team and in the literature, by applying the organometallic approach largely experienced in the group for other metal systems. This method is well-known as an efficient way to obtain well-controlled nanostructures with clean surfaces, important mainly in catalysis.

No description available.

Isocyanates are invaluable bulk chemicals that play a central role in the synthesis of various polymers and provide a key platform for the synthesis of nitrogen-containing molecules such as carbamates and ureas. Unfortunately, isocyanates suffer from high toxicity, low functional group tolerance, and a propensity to undergo deleterious side-reactions. Consequently, blocked (masked) isocyanate derivatives have been the subject of increased interest resulting from their reduced toxicity and exceptional control over isocyanate reactivity. This strategy has largely been relegated to the polymerization literature, although its use in the synthesis of complex urea and carbamate derivatives is well established in synthetic organic chemistry. However, prominent gaps in the blocked isocyanate literature were clear at the outset of this research project. First and foremost, the development of heteroatom-substituted isocyanates, such as N- and O-substituted derivatives, remained relatively scarce despite their potential for the synthesis of important nitrogen-containing derivatives. Furthermore, the additions of carbon-centred nucleophiles on blocked N-, O-, and even C-substituted blocked isocyanates were exceedingly rare. Finally, the use of a blocking group strategy in catalytic transformations of isocyanates remained largely absent from the literature. This was particularly striking given the widespread development of catalytic transformations of isocyanates. As such research efforts began focusing on furthering the development of blocked N-isocyanates as a vital platform for heterocyclic synthesis (chapter 2). Initially, the cascade reactivity of blocked N-iso(thio)cyanates was expanded to incorporate electrophiles such as alkynes (section 2.2). This readily provided access to imidazolone and thiazolidine products. Subsequently, the development of a cascade reaction providing access to 1,2,4-triazin-3(2H)-ones was explored (section 2.3). This provided the first examples of an N-isocyanate cascade which hinged on the use of acid catalysis. Moreover, insight into hydrazone isomerization was gained. Finally, these efforts culminated in the development of cascade reactions providing access to a rare class of 1,2,4-triazinones as well as 5-aminopyridazinones (section 2.4). This provided the first example of a cascade reaction involving a C-C bond formation onto a blocked N-isocyanate derivatives. Furthermore, this development was pivotal in re-focusing attention on the development of general strategies to achieve addition of carbon nucleophiles onto blocked isocyanate derivatives. Towards this end, the development of two strategies to achieve carbon-centred nucleophilic additions on both blocked N- And O-isocyanates were developed (chapter 3). Inspiration from the isocyanate literature led to the development of carboxylic acids as formal carbon nucleophiles (section 3.2). This strategy was found to be quite general for the synthesis of hydroxamates from blocked O-isocyanates. Furthermore, encouraging results were generated on the ability of Grignard reagents to form similar products (section 3.3). Particularly important is the paradigm shift this allows from C-N bond formation to C-C bond formation for the synthesis of hydroxamate derivatives. Furthermore, lead results suggest the potential of this reactivity to translate to blocked N-substituted derivatives, a transformation which had failed with carboxylic acids. Finally, the development of a catalytic amide synthesis from blocked isocyanate precursors was targeted (chapter 4). The use of a blocking group strategy was able to address the current major limitation of isocyanates as amide precursors, that is functional group tolerance (section 4.2). Indeed, a commercially available rhodium catalyst was found to allow efficient amidation of various ambiphilic blocked isocyanate derivatives using arylboroxines as nucleophiles. Mechanistic studies including the use of variable time normalization analysis supported the presence of two alternative kinetic regimes contingent on the reaction conditions employed. Furthermore, these data suggested the success of this transformation, in the case of ambiphilic derivatives, hinged on a rate determining isocyanate release (chapter 4). Finally, initial results strongly support the potential for Boc-carbamates to provide a general platform for amidation in the presence of strong nucleophiles such as primary amines. The potential of a blocking group strategy in catalytic reaction development was further displayed with the development of a palladium catalyzed amidation of blocked derivatives with arylboroxine nucleophiles (section 4.3). Indeed, the use of blocked isocyanates was found to be absolutely key in achieving efficient reactivity with the palladium catalyst. This result, coupled with the sparse reports on blocked isocyanates in catalysis, strongly suggest that the use of such a strategy could allow the development of reactivity otherwise unattainable when using free isocyanates.

The objective of the present work was to study further the effect of varying substituents on the nitrogen atom and on the ring of sulfonamides in the Birch reduction of aromatic sulfonamides, especially with respect to the amount of thiol formed, in the hope that information concerning the initial cleavage step might be discerned.

No description available.

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