Extensive consumption of carbon resources has led to decreasing reserves of fossil fuels and growing concern about global warming. This dilemma has promoted a shift in the economy to develop new long-term, environmentally friendly, and sustainable sources for fuels and chemicals to replace fossil fuel-based sources. Renewable biomass is an ideal alternative, as it is abundant, and relatively cheap. Among current biofuel resources, 5-hydroxymethylfurfural (5-HMF) is a versatile intermediate between biomass-based carbohydrate chemistry and fossil fuel-based industrial organic chemistry, which can be used to synthesize a broad range of chemicals that are currently derived from fossil fuel-based resources. Carbohydrates became the preferred feedstock for high yield production of 5-HMF, and the most convenient route for the synthesis of 5-HMF is the acid-catalyzed dehydration of hexose. Within this context, a variety of processes were developed for the synthesis of 5-HMF from dehydration of fructose involving various solvents, including water, organic solvents, and biphasic systems. Likewise, a range of catalysts were employed, such as homogeneous acid catalysts and metal chlorides, which showed high catalytic activity. Heterogeneous catalysts have also been receiving attention due to their advantages such as easy recovery and recyclability. In the current research, microwave-assisted synthesis of 5-HMF by dehydration of fructose over various acidic porous catalysts, such as periodic mesoporous organosilica (PMO), carbon materials, and metal organic frameworks (MOFs), was investigated. The results showed that the obtained 5-HMF yields were satisfactory, and more importantly highlighted some of the properties of porous heterogeneous catalysts that may improve the production of 5-HMF.

La laine de verre est un matériau utilisé pour l'isolation acoustique et thermique des habitations. Ce matériau est constitué à 95% de fibres de verre et à 5% d'un liant. Bien que ce dernier soit utilisé en quantité très faible dans la formulation du matériau, il est responsable de l'obtention de bonnes propriétés mécaniques en assurant, notamment, l'intégrité structurelle du panneau de laine de verre. Pour préparer ces liants, une résine et des additifs (huile, silicone et silane) sont utilisés. Depuis une cinquantaine d'années, les résines majoritairement utilisées pour la préparation de liant pour la fabrication de la laine de verre sont de type formo-phénolique. Bien que les propriétés mécaniques des panneaux de laine de verre obtenus avec cette résine soient bonnes, il a été nécessaire d'éliminer le formaldéhyde, composé Cancérigène-Mutagène-Reprotoxique, de la formulation. C'est pourquoi de nouvelles résines ont dû être développées. Ces développements ont permis de retenir une résine pH-compatible à base de saccharose et avec des propriétés mécaniques analogues à celles obtenues avec la résine formo-phénolique. Le but de cette thèse est donc d'accéder à une connaissance approfondie des mécanismes réactionnels mis en jeu dans la formation de cette résine pour pouvoir, in fine, en optimiser ses performances / Glass wool is a material used for the acoustic and thermal insulation of dwellings. This material contains 95% of glass fibers and 5% of binder. Although this binder is used in a very small quantity in the formulation, it provides the expected mechanical properties by ensuring the structural integrity of the glass wool panel. To prepare these binders, resin and additives (oil, silicone and silane) are used. For fifty years the resins mostly used for the preparation of glass wool’s binders were the formo-phenolic’s types. Although theses resins provide good mechanical properties of the glass wool panels, it was necessary to remove the formaldehyde, a Carcinogen-Mutagen-Reprotoxic compound, from the formulation. As a consequence, new resins were developed. These developments helped us to retain a pH-compatible resin based on sucrose with mechanical properties as good as formo-phenolic’s resin. So, the aim of this thesis is to investigate the whole chemistry’s mechanism involved in the formation of this resin in order to be able to increase its performance

Purpose. 5-HMF is a potential antisickling agent forming a Schiff-adduct with hemoglobin (Hb). In-vitro studies were designed to identify the metabolic pathways of 5-HMF in human hepatic cytosol, to assess inter-species differences in its hepatic metabolism, and to predict in-vivo PK properties. Moreover, metabolism of 5-HMF in human RBCs was investigated. Finally, in-vitro studies were done to characterize 5-HMF binding kinetics with human Hb and albumin (HSA). Methods. NAD+ reduction was monitored at 340 nm in human hepatic cytosol for 5-HMF (26 mM) and prototypical ADH and ALDH substrates in the presence or absence of their inhibitors. Furthermore, concentration-dependency studies were performed for 5-HMF (1.5-96 mM) in mouse, rat, dog, and human hepatic cytosol and fitted by Michaelis Menten (MM) model. In-vitro-in-vivo-extrapolation (IVIVE) was performed using the well-stirred model. Moreover, metabolic studies of 5-HMF (12-142 mM) in human RBCs were done under similar conditions. Time- and concentration-dependent binding studies were conducted for 5-HMF (5 µM-5 mM), in Hb (217 μM) and HSA (63 and 202 μM) solutions. Ultrafiltered 5-HMF concentrations were measured by a validated HPLC-UV assay. After correction for nonspecific binding, rate constants, binding affinity, and capacity were estimated by nonlinear regression. Results. In human hepatic cytosol, 5-HMF followed MM kinetics with Km: 218(±74) mM and was mainly inhibited by the ALDH inhibitor. In all animal species, 5-HMF exhibited millimolar Km values and is expected to have low hepatic extraction, high oral bioavailability, and first-order PK for relevant blood concentrations. The IVIVE-predicted in-vivo half-lives for 5-HMF were adequate for the mouse and dog but overestimated for humans. In RBCs, 5-HMF had Clintin-vitro of 0.34(± 0.02) ml/min/ml RBCs scaled-up to 9.9 ml/min/kg. Time-dependent binding of 5-HMF was demonstrated for both Hb and HSA. Steady-state studies revealed saturable Hb binding and non-saturable HSA binding. Conclusions. 5-HMF is an ALDH/ADH substrate in hepatic cytosol. Across animal species, 5-HMF is expected to be a low-hepatic-extraction-ratio drug with high oral bioavailability. 5-HMF is subject to RBCs metabolism in human. 5-HMF is expected to show fast association with, but slow dissociation from its drug target, Hb, which may lead to a prolonged in-vivo PD effect.

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Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2017-06-13T18:57:00Z No. of bitstreams: 1 AndersonJoelSchwanke_TESE.pdf: 68952400 bytes, checksum: 183df356ba12677a33625fdc1a455ae1 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2017-06-13T23:49:01Z (GMT) No. of bitstreams: 1 AndersonJoelSchwanke_TESE.pdf: 68952400 bytes, checksum: 183df356ba12677a33625fdc1a455ae1 (MD5) / Made available in DSpace on 2017-06-13T23:49:01Z (GMT). No. of bitstreams: 1 AndersonJoelSchwanke_TESE.pdf: 68952400 bytes, checksum: 183df356ba12677a33625fdc1a455ae1 (MD5) Previous issue date: 2016-12-05 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico (CNPq) / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES) / A s?ntese das ze?litas hier?rquicas de estrutura MWW foram realizadas empregando estrat?gias de soft e hard templates. Os materiais foram caracterizados por diversas t?cnicas como DRX, TG, ICP, Isotermas de adsor??o de N2, MEV, MET e, UV-Vis e FTIR com piridina adsorvida. A estrat?gia por soft template foi realizada empregando surfactantes com diferentes tamanhos de cadeia em diferentes tratamentos (suave e agressivo). Foi observado que o tamanho do surfactante em sinergia de tratamento (suave ou agressivo) influencia na arquitetura final gerando materiais pilarizados, desorganizados e desilicados. De uma forma geral, foi observado que o tratamento agressivo danifica a estrutura, por?m cria regi?es de acessibilidade devido ? quebra de algumas l?minas MWW, resultando em uma atividade catal?tica para convers?o de frutose a 5-hidroximetilfurfural (5-HMF) semelhante aos materiais com tratamento suave. Para as ze?litas com pilares mistos de Si/Nb, a inser??o do metal aumenta a acidez de Lewis devido a incorpora??o de ni?bio. O ni?bio se encontra como esp?cies mononucleares tetra?dricamente coordenado com o sil?cio nos pilares e o seu aumento gradual da quantidade de ni?bio nos pilares acaba por diminuir a mesoporosidade interlamelar. O uso de part?culas de carbono tipo BP 2000 como hard templates em ze?litas tipo MCM-22 foi efetivo e no controle de morfologia microesf?rica. Isto se deve ao procedimento de s?ntese utilizado, em modo din?mico, e particularmente, a forma tortuosa das dos aglomerados de part?culas prim?rias do carbono BP 2000 que interage com os n?cleos zeol?ticos. O crescimento dos cristais se d? em orienta??es aleat?rias, na forma de castelo de cartas com regi?es de meso e macroporos acess?veis em toda a microesfera as quais possuem tamanhos entre 6-10 ?m. O controle da morfologia na forma de microesferas n?o afeta a atividade catal?tica comparado ? s?ntese tradicional da MCM-22. As microesferas na forma acidificadas foram impregnadas com ni?bio e demonstraram sinergia entre a acidez da ze?lita e o metal apresentando atividade catal?tica superior para a convers?o de frutose a 5-HMF ? sua forma acidificada nos primeiros 45 minutos de rea??o. Foi demonstrado que as estrat?gias por soft e hard template s?o atrativas e potencias para a cria??o de porosidade hier?rquica em ze?litas de estrutura MWW. / A s?ntese das ze?litas hier?rquicas de estrutura MWW foram realizadas empregando estrat?gias de soft e hard templates. Os materiais foram caracterizados por diversas t?cnicas como DRX, TG, ICP, Isotermas de adsor??o de N2, MEV, MET e, UV-Vis e FTIR com piridina adsorvida. A estrat?gia por soft template foi realizada empregando surfactantes com diferentes tamanhos de cadeia em diferentes tratamentos (suave e agressivo). Foi observado que o tamanho do surfactante em sinergia de tratamento (suave ou agressivo) influencia na arquitetura final gerando materiais pilarizados, desorganizados e desilicados. De uma forma geral, foi observado que o tratamento agressivo danifica a estrutura, por?m cria regi?es de acessibilidade devido ? quebra de algumas l?minas MWW, resultando em uma atividade catal?tica para convers?o de frutose a 5-hidroximetilfurfural (5-HMF) semelhante aos materiais com tratamento suave. Para as ze?litas com pilares mistos de Si/Nb, a inser??o do metal aumenta a acidez de Lewis devido a incorpora??o de ni?bio. O ni?bio se encontra como esp?cies mononucleares tetra?dricamente coordenado com o sil?cio nos pilares e o seu aumento gradual da quantidade de ni?bio nos pilares acaba por diminuir a mesoporosidade interlamelar. O uso de part?culas de carbono tipo BP 2000 como hard templates em ze?litas tipo MCM-22 foi efetivo e no controle de morfologia microesf?rica. Isto se deve ao procedimento de s?ntese utilizado, em modo din?mico, e particularmente, a forma tortuosa das dos aglomerados de part?culas prim?rias do carbono BP 2000 que interage com os n?cleos zeol?ticos. O crescimento dos cristais se d? em orienta??es aleat?rias, na forma de castelo de cartas com regi?es de meso e macroporos acess?veis em toda a microesfera as quais possuem tamanhos entre 6-10 ?m. O controle da morfologia na forma de microesferas n?o afeta a atividade catal?tica comparado ? s?ntese tradicional da MCM-22. As microesferas na forma acidificadas foram impregnadas com ni?bio e demonstraram sinergia entre a acidez da ze?lita e o metal apresentando atividade catal?tica superior para a convers?o de frutose a 5-HMF ? sua forma acidificada nos primeiros 45 minutos de rea??o. Foi demonstrado que as estrat?gias por soft e hard template s?o atrativas e potencias para a cria??o de porosidade hier?rquica em ze?litas de estrutura MWW.