La distillation réactive est un exemple emblématique de l’intensification de procédés. Cependant, le couplage réaction/séparation génère des complexités importantes en termes de dynamique, de contrôle et de supervision qui constituent une barrière pour leur mise en œuvre industrielle. Ces aspects doivent être considérés dès la phase de conception sous peine de concevoir une colonne difficilement contrôlable. Une méthodologie existante est étendue afin d’y intégrer les aspects de contrôlabilité et de diagnosticabilité. L’étape de conception étudie les courbes de résidu et extractives réactives, identifie les paramètres opérationnels et propose des configurations de colonne respectant les spécifications. La meilleure configuration est choisie sur des critères de contrôlabilité par l’analyse de différents indicateurs quantitatifs et qualitatifs identifiés à l’aide de simulations en régime permanent et dynamique. La méthodologie est appliquée à la production industrielle d’acétate d’éthyle. Deux campagnes expérimentales ont permis de fiabiliser le modèle de simulation de la colonne. La méthodologie permet d’identifier les sensibilités et montre que il est possible d’agir sur les trois degrés de liberté de la colonne double alimentation pour atteindre les spécifications industrielles ; les variables contrôlées sont sélectionnées dans des sections spécifiques, similaires pour différentes configurations de colonne. Concernant le diagnostic, l’utilisation de capteurs de composition semble la plus pertinente mais la complexité de leur utilisation industrielle (cout) peut être contournée par la sélection d’un nombre plus important de capteurs de température judicieusement positionnés. Les résultats de contrôlabilité et de diagnosticabilité sont en cohérence et bien intégrés dans la conception des colonnes réactives. / Reactive distillation involves complexities on process dynamics, control and supervision. This work proposes a methodology integrating controllability and diagnosability as from conceptual design. The choice of the most appropriate feasible configuration is conducted though an indices-based method, regarding steady-state and dynamic simulations, for the ethyl acetate production. Experimental campaigns were performed to acquire reliable models. The methodology highlights the process sensitivities and shows that three degrees of freedom of the double-feed column can be manipulated to ensure the industrial specifications; the controlled variables are selected at similar specific locations for all column configurations. Concerning diagnosis, the use of composition sensors seems to be the most appropriate solution, but the same performances can be reached with more temperature sensors judiciously placed.

The knowledge about the use of medicinal plants by the population contributed decisively to the modern therapy and the discovery of important mechanisms related to the process of transmission and treatment of pain. A plant widely used in folk medicine is Mirabilis jalapa L. (Nyctaginaceae). The infusion of its leaves is used for the treatment of inflammatory and painful diseases; however, there are no studies confirming its popular use. In this study, we evaluated the potential antinociceptive effects of Mirabilis jalapa in mice. Oral administration (p.o.) of the crude hidroetanolic extracts from leaves and stems inhibited the nociception with ID50 values of 5.5 (2.3 to 13.1) and 18.0 (11.3 to 28.5) mg/kg in a model of acute pain induced by chemical stimulation (test of writhing induced by acetic acid). Among the fractions tested, the ethyl acetate fraction from the leaves (Eta, 10 mg/kg, p.o.) was more effective and potent to induce antinociception with ID50 value of 1.1 (0.6 to 2.1) mg/kg. Thus, this fraction was chosen for further studies. Furthermore, these extracts also inhibited the nociception induced by thermal stimulation (tail-flick test). In addition, Eta (10 mg/kg, p.o.) produced antinociception in models of pain related to arthritis (caused by Freund's Complete Adjuvant (CFA)), neuropathic pain (caused by partial sciatic nerve ligation) and post-surgical pain (induced by incision in the paw of mice). Only the repetead administrations of Eta (10 mg/kg, p.o.) cause a decrease in paw edema produced by CFA. The antinociceptive effect of Eta (10 mg/kg, p.o.) was not reversed by pretreatment with naloxone (2 mg/kg, i.p.), but by atropine (5 mg/kg, s.c.) or mecamylamine (0.001 mg/kg, s.c.). As the participation of the cholinergic system in antinociception was induced by this fraction, we determined the effect of Eta on the activity of acetylcholinesterase (AChE) in vitro and ex vivo. The in vitro activity of AChE in blood and spinal cord of animals was not altered by Eta (1 and 10 mg/mL). In the ex vivo assay, an increase of enzyme activity in the spinal cord of mice treated with CFA, which was completely reversed with the administration of Eta (10 mg/kg, p.o.), was observed. With regard to adverse effects, Eta (10 mg/kg, p.o.) did not alter locomotor activity, body temperature or gastrointestinal transit, nor produced gastric lesions. These results demonstrated that M. jalapa shows antinociceptive activity in mice, confirming its popular use as an analgesic. / O conhecimento sobre o uso de plantas medicinais pela população contribuiu decisivamente para a terapêutica moderna e para a descoberta de importantes mecanismos relacionados com o processo de transmissão e o tratamento da dor. Uma planta muito utilizada pela medicina popular é a Mirabilis jalapa L. (Nyctaginaceae). A infusão das suas folhas é utilizada para o tratamento de doenças inflamatórias ou dolorosas, mas ainda não existem estudos confirmando o seu uso popular. No presente trabalho, foi avaliado o potencial antinociceptivo da Mirabilis jalapa em camundongos. A administração oral (v.o.) dos extratos brutos hidroetanólicos das folhas e de caules foi efetiva em inibir a nocicepção com valor de DI50 de 5,5 (2,3 13,1) e 18,0 (11,3 28,5) mg/kg, em um modelo de dor aguda induzida por estímulo químico (teste das contorções abdominais induzidas por ácido acético). Entre as frações testadas, a fração acetato de etila obtida das folhas (Eta, 10 mg/kg, v.o.) foi a mais potente em induzir a antinocicepção com valor de DI50 de 1,1 (0,6 2,1) mg/kg. Por isso, esta fração foi escolhida para a realização de estudos posteriores. Além disso, esses extratos também inibiram a nocicepção induzida por estímulo térmico (teste da imersão de cauda). Em adição, a Eta (10 mg/kg, v.o.) produziu antinocicepção em modelos de dor relacionada a artrite (causada por Adjuvante Completo de Freund (ACF), dor neuropática (provocada pela ligação parcial do nervo ciático) e dor pós-cirúrgica (induzida por incisão na pata de camundongos). Somente a administração repetida da Eta provocou uma diminuição do edema de pata induzido por ACF. Entretanto, a Eta não alterou o aumento dos níveis de interleucina 1-β produzido por ACF. O efeito antinociceptivo da Eta (10 mg/kg, v.o.) não foi revertido pelo pré-tratamento com naloxona (2 mg/kg, i.p.), mas sim, por atropina (5 mg/kg, s.c.) ou mecamelamina (0,001 mg/kg, s.c.). Como houve a participação do sistema colinérgico na antinocicepção induzida por esta fração, foi determinado o efeito da Eta sobre a atividade da acetilcolinesterase (AChE) in vitro e ex vivo. A atividade in vitro da acetilcolinesterase no sangue e na medula espinhal dos animais não foi alterada pela Eta (1 e 10 μg/mL). Já no ensaio ex vivo, houve um aumento da atividade desta enzima na medula espinhal de camundongos tratados com ACF, que foi completamente revertida com a administração da Eta (10 mg/kg, v.o.). Com relação aos efeitos adversos, a Eta (10 mg/kg, v.o.) não alterou a atividade locomotora, temperatura corporal, trânsito gastrintestinal e nem produziu lesões gástricas. Estes resultados demonstraram que M. jalapa apresenta atividade antinociceptiva em camundongos, confirmando o seu uso popular como analgésico.

Made available in DSpace on 2016-06-02T19:56:38Z (GMT). No. of bitstreams: 1 2958.pdf: 1485003 bytes, checksum: 13ecfdc9482ce660829ef15f2081578e (MD5) Previous issue date: 2010-03-10 / Financiadora de Estudos e Projetos / The ethanol dehydrocoupling in ethyl acetate distinguishes among the reactions of alcohol transformation in products with higher added value. Due to the possibility of obtaining ethanol from biomass in Brazil, the production of ethyl acetate is of great interest, being their production very economical. The ethanol dehydrocoupling in ethyl acetate was studied over Cu/ZrO2 catalysts prepared by impregnation method followed by calcinations in air. The samples with different Cu loadings were characterized by thermal analyze, X-Ray powder diffraction, determination of the specific surface area, temperature-programmed reduction (TPR), decomposition of N2O and X-Ray photoelectron spectroscopy (XPS). TPR results showed the formation of low temperature reduction Cu species (peaks α1, α2 e β) predominant at low loadings of supported Cu in ZrO2, these species are attributed to CuO highly dispersed on support. The increase of Cu loading caused the formation of CuO bulk species with high temperature reduction (peaks γ1 e γ2). XPS results for Cu/ZrO2 reduced catalysts showed that an increase in the Cu loading caused a shift in the Cu 2p3/2 peak to regions of lower biding energy. The spectra of Cu Auger region suggest that a decrease in the Cu loading increases the ratio of Cu+/Cuo species. Catalytic tests for dehydrocoupling reaction of ethanol were carried out at atmospheric pressure and showed an increasing activity per Cu site for ethyl acetate formation with the increase in the dispersion of supported Cu. Furthermore, the by-products formation due the acetaldehyde via aldol condensation occurs on the ZrO2 support surface. Also, it could be seen that catalysts with Cu loading up to 20% showed an increase in the ethyl acetate selectivity with an increase in the Cu loading. This can be attributed to the higher ZrO2 coating by active phase providing the suppression of by-products that are formed via aldol condensation. / O desidroacoplamento do etanol em acetato de etila destaca-se dentre as reacoes de transformacao de alcoois em produtos de maior valor agregado. Devido a abundancia de etanol no Brasil e a possibilidade de sua obtencao a partir da biomassa, a producao de acetato de etila desperta grande interesse, sendo a sua producao muito economica. O desidroacoplamento do etanol em acetato de etila foi estudado sobre catalisadores de Cu/ZrO2 preparados pelo metodo de impregnacao, seguidos de calcinacao em ar. As amostras com diferentes cargas de Cu foram caracterizadas por analise termica, difracao de Raios X, determinacao da area superficial especifica, reducao a temperatura programada (TPR), decomposicao do N2O e espectroscopia de fotoeletrons excitados por Raios X (XPS). Resultados de TPR mostraram a formacao de especies de cobre de baixa temperatura de reducao (picos α1, α2 e β) predominantes em baixas cargas de Cu suportados em ZrO2, estas especies sao atribuidas ao CuO altamente disperso no suporte. Com o aumento da carga de Cu obteve-se a formacao de especies de CuO massico de alta temperatura de reducao (picos γ1 e γ2). Resultados de XPS para catalisadores de Cu/ZrO2 reduzidos revelaram que com o aumento da carga de cobre suportado houve o deslocamento do pico da regiao Cu 2p3/2 para regioes de menor energia de ligacao. Os espectros da regiao Auger do Cu sugerem que com a diminuicao da carga de Cu tem-se o aumento da razao das especies Cu+/Cuo. Ensaios cataliticos para a reacao de desidroacoplamento do etanol foram realizados a pressao atmosferica e mostraram o aumento da atividade por sitio de Cu para a formacao de acetato de etila com o aumento da dispersao do cobre no suporte. Sobre a superficie do suporte ZrO2 ocorre a formacao de subprodutos devido a condensacao do acetaldeido via condensacao aldolica. Para catalisadores com carga de Cu de ate 20% verifica-se o aumento da seletividade a acetato de etila com o aumento da carga de cobre, em decorrencia do aumento do grau de recobrimento da ZrO2 pela a fase ativa proporcionando a supressao de subprodutos formados via condensacao aldolica.

A transesterificação metílica em meio homogêneo é catalisada por bases, tais como hidróxidos e alcóxidos de sódio ou potássio e se processa em baixa temperatura de reação, mesmo em escala industrial. A utilização de catalisadores formados por sólidos básicos aparece como uma alternativa promissora aos processos homogêneos convencionais, tendo em vista as inúmeras vantagens como a redução da ocorrência das reações indesejáveis de saponificação e redução de custos dos processos pela diminuição do número de operações associadas. Em estudos anteriores realizados pelo grupo, catalisadores a base de Mg/La com diferentes composições químicas (9:1, 1:1 e 1:9) mostraram-se promissores para a obtenção de ésteres metílicos via reação de transesterificação, porém não foi possível fazer uma correlação entre atividade catalítica e as propriedades físico-químicas quando toda a série foi considerada. Assim, a realização de um estudo de caráter fundamental, baseado em reações modelo e uso de moléculas sonda, permite avançar no entendimento das propriedades de superfície destes catalisadores. Portanto, o presente trabalho estuda a reação entre metanol e acetato de etila em catalisadores a base de Mg/La utilizando espectroscopia de reflectância difusa no infravermelho com transformada de Fourier (DRIFTS) acoplada a espectrometria de massas (MS) identificando os intermediários e produtos formados para determinar a rota reacional. As análises de difração de raios X mostram que os precursores são predominantemente compostos por carbonatos hidratados de magnésio (Mg/La 1:1 e 9:1) e de lantânio (Mg/La 1:9). Os perfis de decomposição térmica e difratogramas de raios X obtidos a partir de tratamento térmico in situ indicaram que estes carbonatos se decompõem apenas a partir de 750 C. As análises de Dessorção a Temperatura Programada realizadas com moléculas sonda, metanol e acetato de etila, mostraram a adsorção em maior quantidade do metanol independente da composição química do sólido. A partir dos resultados obtidos por DRIFTS-MS foi proposta uma rota reacional para a reação de transesterificação do acetato de etila e metanol, que ocorre via adsorção do metanol e do acetato de etila na superfície do catalisador, seguida da formação de um intermediário tetraédrico formado pelas moléculas adsorvidas, que sofre um rearranjo formando etanol, acetato de metila, acetona e metano. Simultaneamente, parte do metanol adsorvido como metoxi monodentado é desidrogenado formando formiatos que são dessorvidos na forma de formaldeído e decompostos formando CO2 e H2 / The methylic transesterification of vegetable oils catalyzed by sodium or potassium hydroxides or alkoxides is carried out in homogeneous media at a low reaction temperature, even on an industrial scale. However, the homogeneous reaction has some disadvantages such as the sensitivity of the catalyst to the presence of free fatty acids and/or water in the oil feedstock, which causes the occurrence of undesirable saponification reactions. On the other hand, the use of basic solid catalysts appears as a promising alternative to conventional homogeneous processes, since it reduces the occurrence of undesirable reactions of saponification and decreases the process costs due to the reduction of the number of operations associated. In a previous studies of the group, Mg/La catalysts with different chemical compositions (9:1, 1:1 and 1:9) showed good results for the production of methyl esters via transesterification reaction. However, it was not possible to make a correlation between catalytic activity and the basic properties when the whole series was considered. Therefore, the realization of a fundamental study based on model reactions and the use of probe molecules may lead to the comprehension of the surface properties of these catalysts. Thus, in this work, the reaction between methanol and ethyl acetate catalyzed by a series of Mg/La-catalysts was studied using diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) coupled to mass spectrometry (QMS) aiming at identify the intermediates and products formed to determine the reaction route. The analysis of X-ray diffraction showed that the precursors are mainly hydrated carbonates of magnesium (Mg/La 1:1 and 9:1) and lanthanum (Mg/La 1:9). The TG profiles and in situ X-ray difratograms obtained during the thermal decomposition of the precursors indicate that these carbonates decompose at 750 C or above. Temperature Programmed Desorption analysis carried out with probe molecules, methanol and ethyl acetate, showed a higher amount of methanol adsorbed on the catalyst surface. From the results obtained by DRIFTS-MS a reaction route for the transesterification reaction of methanol and ethyl acetate was proposed. The reaction occurs via adsorption of methanol and ethyl acetate on the catalyst surface. These adsorbed species react forming an adsorbed tetrahedral intermediate which undergoes rearrangement producing ethanol, methyl acetate, acetone and methane. Simultaneously, the methanol adsorbed as a monodentate methoxy specie is dehydrogenated forming formates species that are decomposed in CO2 and H2

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / One of the promising ways for the residues utilization is through the development of biotechnological processes for the production of a large number of metabolites of industrial interest, such as the production of bioaromas. The fungus Ceratocystis fimbriata has the potential to synthesis of esters producing varieties of flavor compounds such as ethyl acetate, responsible for a diversity of fruit flavors. The objective this work was utilize and evaluate the biotechnological potential of cassava rind, one of the agro-industrial waste more produced in the Sergipe state, for the production of ethyl acetate through the solid state fermentation. All procedure performed obeyed an experimental design of eleven experiments corresponding to an experimental design 22 trials plus 4 axial points and three repetitions at the central point, with the variable sample mass and moisture content. The volatile compound ethyl acetate was quantified by headspace analysis on a gas chromatograph and it was found that the best experiment for the production of ethyl acetate was (91,92 μmol.L-1) with 50% humidity and 14:23 g weight dried for 48 hours fermentation. As of the best result was done other fermentation for separating the aroma using NaCl at a concentration of 5%, 10%, 15%, 20%, 25%, 30% and 35%. It was observed that NaCl concentration of 30% obtained best value (3303,60 μmol.L-1). This result has been done an increased scale to verify the influence of producing the compound ethyl acetate in a larger surface area where the experiments were performed in 1000 ml Erlenmeyer flask (10%, 20%, 30 % of the quantity of inoculum) and 2000 ml Erlenmeyer flask (50% of the quantity of inoculum). Chromatographic analysis found that 30% of saline best recovered the ethyl acetate in a 1000 ml Erlenmeyer flask with 30% inoculum (19,38 μmol.L-1). / Uma das formas promissoras para o aproveitamento de resíduos é através do desenvolvimento de processos biotecnológicos para produção de um grande número de metabólitos de interesse industrial, como por exemplo, a produção de bioaromas. O fungo Ceratocystis fimbriata tem potencial para síntese de ésteres produzindo variedades de compostos de aromas, como o acetato de etila, responsável por umas diversidades de aromas de frutas. O objetivo deste trabalho foi aproveitar e avaliar o potencial biotecnológico da casca de mandioca, um dos resíduos agroindustriais mais produzidos no estado de Sergipe, para produção de acetato de etila através da fermentação em estado sólido. Todo o procedimento realizado obedeceu a um planejamento experimental de onze experimentos que corresponde um planejamento experimental 22 ensaios acrescidos de 4 pontos axiais e 3 repetições no ponto central, tendo como variáveis a massa da amostra e o teor de umidade. O composto volátil acetato de etila foi quantificado através da análise de headspace no cromatógrafo a gás e foi detectado que o melhor experimento para produção do acetato de etila foi (91,92 μmol.L-1) com 50% de umidade e 14,23 g de massa seca durante 48 horas de fermentação. A partir do melhor resultado obtido foi realizado outra fermentação para separação do aroma utilizando NaCl numa concentração de 5%, 10%, 15%, 20%, 25%, 30% e 35%. Foi observado que a concentração de NaCl de 30% obteve melhor valor (3303,60 μmol.L-1). Com este resultado, foi realizado um aumento de escala para verificar a influência da produção do composto acetato de etila numa maior área superficial onde os experimentos foram realizados em erlenmeyer de 1000 ml (10%, 20%, 30% de quantidade de inóculo) e 2000 ml (50% de quantidade de inóculo). A análise cromatográfica detectou que a solução salina de 30% recuperou melhor o acetato de etila no erlenmeyer de 1000 ml com 30% de inóculo (19,38 μmol. L-1).

Submitted by isabela.moljf@hotmail.com (isabela.moljf@hotmail.com) on 2017-04-27T15:30:59Z No. of bitstreams: 1 daniellemariadeoliveiraaragao.pdf: 4293901 bytes, checksum: 9fe0e48b323213abc9a30b33ba1f90db (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2017-05-12T15:50:14Z (GMT) No. of bitstreams: 1 daniellemariadeoliveiraaragao.pdf: 4293901 bytes, checksum: 9fe0e48b323213abc9a30b33ba1f90db (MD5) / Made available in DSpace on 2017-05-12T15:50:14Z (GMT). No. of bitstreams: 1 daniellemariadeoliveiraaragao.pdf: 4293901 bytes, checksum: 9fe0e48b323213abc9a30b33ba1f90db (MD5) Previous issue date: 2015-02-27 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Diabetes melito engloba uma série de alterações metabólicas que acarretam um estado crônico de hiperglicemia. Buscando novas alternativas para seu tratamento, muitas espécies de plantas conhecidas na medicina popular pelas propriedades hipoglicemiantes têm sido avaliadas. Entre essas espécies está Cecropia pachystachya Trécul (URTICACEAE), uma planta nativa do Brasil, cujos nomes populares são embaúba, imbaíba, umbaúba, árvore-de-preguiça, barbeira, torém. Nesse contexto, o presente estudo teve como objetivo avaliar o potencial hipoglicemiante, antioxidante e toxicológico das folhas de Cecropia pachystachya. Inicialmente foram preparados dois extratos das folhas dessa espécie, metanólico (EM) e em acetato de etila (EAE). Ambos os extratos foram submetidos à análise quantitativa dos marcadores moleculares e, posteriormente, foi avaliado o efeito hipoglicemiante de cada um deles. EAE foi ncorporado a uma formulação farmacêutica líquida (FF). EM, EAE e FF foram utilizados para o tratamento de ratos da linhagem Wistar normais e induzidos ao diabetes por estreptozotocina. A evolução desses tratamentos foi avaliada através de medidas mensais de glicemias de jejum, além de acompanhamento de peso corporal e consumos de água e ração. Ao final de seis meses, os animais foram eutanasiados e amostras de sangue e órgãos foram coletadas para análises bioquímicas, antioxidante e histopatológica. Foram ainda avaliados os efeitos de FF após a interrupção do tratamento e o efeito do pré-tratamento com FF na indução de ratos com estreptozocina. A análise do perfil cromatográfico de EM e EAE revelou a presença de três marcadores moleculares, ácido clorogênico, isoorientina e orientina. Na análise quantitativa foram observados maiores teores dos flavonoides isoorientina e orientina em EAE. Os extratos padronizados foram administrados em ratos diabéticos ao longo de seis meses, mostrando reduções significativas tanto para EM (56%) quanto para EAE (69%). No entanto, EAE apresentou redução significativa da glicemia já no primeiro mês de tratamento, além de apresentar resultados relevantes em todos os parâmetros antioxidantes avaliados. O tratamento crônico com FF proporcionou uma redução de aproximadamente 70% da glicemia de jejum, ao final dos seis meses, em relação à glicemia inicial desses mesmos animais. Após a interrupção desse tratamento, as glicemias de animais diabéticos foram mantidas em níveis normais. Além disso, o pré-tratamento de ratos normais com FF promoveu proteção sobre as células B-pancreáticas durante a indução do diabetes utilizando estreptozocina. Os resultados mostraram que a FF desenvolvida a partir da espécie Cecropia pachystachya pode ser indicada na preparação de um fitoterápico para auxiliar no tratamento do diabetes melito. / Diabetes mellitus comprises a series of metabolic changes that lead to a chronic state of hyperglycemia. Seeking new alternatives for their treatment, many species of plants known in folk medicine for hypoglycemic properties have been evaluated. Among these species is Cecropia pachystachya Trécul (Urticaceae), a plant native to Brazil, whose common names are embaúba, imbaíba, umbaúba, tree-of-laziness, barbeira, Torem. In this context, the present study aimed to evaluate the potential hypoglycemic, antioxidant and toxicology of Cecropia leaves pachystachya. Initially were prepared two extracts from the leaves of this species, methanol (EM) and ethyl acetate (EAE). Both extracts were subjected to quantitative analysis of molecula markers and subsequently evaluated the hypoglycemic effect of each. EAE was incorporated into a liquid pharmaceutical formulation (FF). MS, EAE and FF were used for the treatment of normal Wistar rats and streptozotocin-induced diabetes. The evolution of these treatments was evaluated through monthly measurements of fasting glucose, and body weight monitoring and water and feed consumption. After six months, the animals were euthanized and blood samples and organs were collected for biochemical, antioxidant and histopathological analysis. We also assessed the effects of FF after discontinuation of treatment and the effect of pretreatment with inducing FF in rats with streptozocin. Analysis of the chromatographic profile of MS and EAE showed the presence of three molecular markers, chlorogenic, orientin and isoorientina acid. The quantitative analysis showed higher levels of flavonoids orientin isoorientina and in EAE. Standardized extracts were administered to diabetic rats over six months, showing significant reductions for both MS (56%) and against EAE (69%). However, EAE had a significant reduction of blood glucose in the first month of treatment, and provide relevant results in all evaluated parameters antioxidants. Chronic treatment with FF was reduced by approximately 70% of fasting glucose at the end of six months from the initial blood glucose of those animals. After discontinuation of treatment, the glycemia of diabetic animals were maintained at normal levels. In addition, pretreatment of mice with normal FF provided protection for pancreatic B-cells in diabetes induced using streptozotocin. The results show that FF developed from Cecropia pachystachya species can be indicated in a herbal preparation to aid in the treatment of diabetes mellitus.

La production mondiale de solvants représente environ 28 millions de tonnes, dont 5 millions en Europe. L’industrie des peintures et des revêtements en est la principale consommatrice (46 % des solvants produits). Dans ce domaine, les solvants les plus utilisés sont l'acétate d'éthyle, l'acétate de butyle et la méthyl éthyl cétone. Ces molécules sont actuellement synthétisées industriellement à partir de substrats d’origine pétrochimique en présence de catalyseurs homogènes et dans des conditions énergivores. Afin de réduire l’impact environnemental des peintures et revêtements, la substitution de ces solvants issus du pétrole par leurs équivalents bio sourcés a été étudiée dans le cadre du projet européen ECOBIOFOR (FP7/2007-2013/Grant Agreement no 605215), dans lequel se sont inscrits ces travaux de thèse. Ainsi, l’objectif de cette thèse a été de développer, à partir de synthons renouvelables, des procédés de production de ces trois solvants simples à mettre en oeuvre, peu coûteux et respectueux des principes de la chimie verte. Pour la production des acétates d’éthyle et de butyle, deux voies de synthèse ont été étudiées en présence d’une résine échangeuse d'ions comme catalyseur hétérogène. La première voie utilise de l'acide acétique et l’alcool biosourcé correspondant (éthanol ou le butan-1-ol); la seconde met en jeu l’anhydride acétique à la place de l’acide acétique. Dans ces synthèses, quatre résines ont été testées. Des études cinétiques et thermodynamiques ont permis de choisir la résine la plus performante et les conditions de réaction les plus adaptées. Cette étude a finalement permis de proposer un procédé de coproduction des deux acétates efficace et innovant dans lequel la purification des acétates est facilitée, la production de déchets et coproduits est réduite et le recyclage de la résine est possible. L'évaluation des performances des acétates synthétisés dans des formulations de laques nitrocellulosiques et de vernis polyuréthanes a permis de montrer que ces molécules répondent au cahier des charges en terme de séchage, viscosité, formation de film, brillance et adhérence. Enfin, le bénéfice environnemental du processus de coproduction a été mis en évidence par le calcul des métriques de la chimie verte et l'analyse du cycle de vie des esters produits. De plus, l'influence de l'origine des alcools, biosourcés ou pétrochimiques, sur l’impact environnemental a été évaluée. L’impact sur le changement climatique est réduit avec l’utilisation des synthons bio-sourcés. Pour la synthèse de la méthyl éthyl cétone, nous avons décidé d’étudier la réaction de décarboxylation de l’acide lévulinique, molécule plateforme biosourcée disponible et peu coûteuse. Contrairement au principal procédé industriel qui repose sur la déshydrogénation du butan-2-ol d'origine fossile, la méthode développée dans ces travaux utilise des conditions plus respectueuses de l’environnement puisqu’elle est réalisée dans l’eau en présence de persulfate de potassium et d’un sel d'argent à une température raisonnable (100°C). L'évaluation du rôle de chacun des réactifs a permis de proposer un mécanisme réactionnel complexe de cette synthèse. L'étude de l’évolution des espèces en phase solide réalisés par diverses analyses spectroscopiques (RMN du solide, DRX, XPS, AES et MEB) a permis de mettre en évidence les espèces impliquées dans la décarboxylation et finalement de proposer une méthode permettant d’obtenir des conversions et des rendements élevés. / Global solvent production accounts for about 28 million tonnes, including 5 million tonnes in Europe. The paint and coating industry is the main consumer (46% of the solvents produced). In this sector, the most used solvents are ethyl acetate, butyl acetate and methyl ethyl ketone. These molecules are currently synthesized industrially from petrochemical substrates in the presence of homogeneous catalysts and under energy-consuming conditions. In order to reduce the environmental impact of paints and coatings, the substitution of these fossil-based solvents by their bio-based equivalents has been studied in the framework of the European project ECOBIOFOR (FP7/2007-2013/Grant Agreement no 605215), in which this thesis work was inscribed. Thus, the objective of this thesis was to develop production processes for these three solvents that would start from renewable synthons and would be simple to implement, inexpensive and respectful of the principles of green chemistry. For the production of ethyl and butyl acetates, two synthetic routes have been studied in the presence of an ion exchange resin as a heterogeneous catalyst. The first route uses acetic acid and the corresponding bio-based alcohol (ethanol or butan-1-ol); the second involves acetic anhydride instead of acetic acid. Kinetic and thermodynamic studies have led to select the most efficient resin and the most suitable reaction conditions. This study has finally allowed to propose an efficient and innovative coproduction process for the two targeted acetates in which their purification is facilitated, the production of waste and co-products is reduced and the recycling of the resin is possible. The evaluation of the performance of the synthesized acetates in nitrocellulose lacquer and polyurethane varnish formulations has shown that these molecules meet the specifications in terms of drying, viscosity, film formation, gloss and adhesion. Finally, the environmental benefit of the co-production process was highlighted by the calculation of green metrics and the life cycle assessment (LCA) of the produced esters. Furthermore, the influence of the origin of alcohols (bio-based or petrochemical) on the environmental impact was evaluated. The impact on climate change is reduced through the use of bio-sourced synthons. For the synthesis of methyl ethyl ketone, we decided to study the decarboxylation reaction of levulinic acid, which is a bio-based platform molecule available and inexpensive. Unlike the main industrial process, which relies on the dehydrogenation of butan-2-ol from fossil origin, the method developed in this work uses conditions that are more respectful of the environment since the reaction is carried out in water in the presence of potassium persulfate and a silver salt at a moderate temperature (100°C). The evaluation of the role of each of the reagents allowed us to propose a complex reaction mechanism for this reaction. The study of the evolution of the solid phase species carried out through various spectroscopic analyzes (SSNMR, XRD, XPS, AES and SEM) made it possible to highlight the species involved in the decarboxylation and finally to propose a method to obtain high conversions and yields.

The static equilibrium isothermal sorption of dioxane, ethyl acetate, and methanol vapors by POM polyoxometalates with the structure of buckyball (Mo132, Mo72Fe30) and torus (Mo138), and also polymer-salt compositions containing POM were studied. The changes in the chemical potentials of the components and the Gibbs energy of the interaction of POMs, polymers, and compositions with low molecular weight liquids are calculated. The Gibbs energies and entropies of interaction of the components of the POM – polymer systems are estimated. The stability of the POM structure before and after sorption was investigated by IR spectroscopy. It was established that all investigated POMs exhibit the highest sorption capacity for dioxane, the lowest for ethyl acetate. Mo132 exhibits maximum affinity for sorbates, Mo72Fe30 exhibits a minimum affinity, and Mo138 occupies an intermediate position. It was established that PVP and PVA adsorb methanol in significantly larger quantities compared with compositions containing POM. The same rule is observed for PVP-POM systems in the case of dioxane. PVA practically does not absorb dioxane, but the introduction of POM in films of polyvinyl alcohol leads to the appearance of the sorption ability of the film. For all compositions a decrease in the Gibbs energy of the interaction of components and an increase in entropy were found, which can be associated with loosening and partial destruction of the crystal structure of the POM when polymer chains are introduced into it. The structure of polyoxomolybdates was found to be stable in dioxane vapors, and is also preserved in polymer-salt compositions before and after sorption. / Изучена статическая равновесная изотермическая сорбция паров диоксана, этилацетата и метанола полиоксометаллатами ПОМ со структурой букибола (Mo132, Mo72Fe30) и тора (Mo138), а также полимерно-солевыми композициями, содержащими ПОМ. Рассчитаны изменения химических потенциалов компонентов и энергии Гиббса взаимодействия ПОМов, полимеров, композиций с низкомолекулярными жидкостями. Оценены энергии Гиббса и энтропии взаимодействия компонентов систем ПОМ – полимер. Методами ИК- спектроскопии исследована стабильность структуры ПОМ до и после сорбции. Установлено, что наибольшую сорбционную способность все исследованные ПОМ проявляют к диоксану, наименьшую – к этилацетату. Максимальное сродство к сорбатам проявляет Mo132, минимальное – Mo72Fe30, Mo138 занимает промежуточное положение. Установлено, что ПВП и ПВС сорбируют метанол в существенно больших количествах по сравнению с композициями, содержащие ПОМ. Такая же закономерность наблюдается для систем ПВП – ПОМ в случае диоксана. ПВС практически не поглощает диоксан, но введение ПОМ в пленки поливинилового спирта приводит к возникновению сорбционной способности пленки. Для всех композиций ПОМ -полимер обнаружено уменьшение энергии Гиббса взаимодействия компонентов и возрастание энтропии, которое может быть связно с разрыхлением и частичным разрушением кристаллической структуры ПОМ при внедрении в нее полимерных цепей. Обнаружено, что структура полиоксомолибдатов стабильна в парах диоксана, а также сохраняется в полимерно-солевых композициях до и после сорбции.

In this work, the solubility of butyl paraben in 7 pure solvents and in 5 different ethanol-water mixtures has been determined from 1 ˚C to 50 ˚C. The solubility of ethyl paraben and propyl paraben in various solvents has been determined at 10 ˚C. The molar solubility of butyl paraben in pure solvents and its thermodynamic properties, measured by Differential Scanning Calorimetry, have been used to estimate the activity of the pure solid phase, and solution activity coefficients. More than 5000 nucleation experiments of ethyl paraben, propyl paraben and butyl paraben in ethyl acetate, acetone, methanol, ethanol, propanol and 70%, 90% ethanol aqueous solution have been performed. The induction time of each paraben has been determined at three different supersaturation levels in various solvents. The wide variation in induction time reveals the stochastic nature of nucleation. The solid-liquid interfacial energy, free energy of nucleation, nuclei critical radius and pre-exponential factor of parabens in these solvents have been determined according to the classical nucleation theory, and different methods of evaluation are compared. The interfacial energy of parabens in these solvents tends to increase with decreasing mole fraction solubility but the correlation is not very strong. The influence of solvent on nucleation of each paraben and nucleation behavior of parabens in each solvent is discussed. There is a trend in the data that the higher the boiling point of the solvent and the higher the melting point of the solute, the more difficult is the nucleation. This observation is paralleled by the fact that a metastable polymorph has a lower interfacial energy than the stable form, and that a solid compound with a higher melting point appears to have a higher solid-melt and solid-aqueous solution interfacial energy. It has been found that when a paraben is added to aqueous solutions with a certain proportion of ethanol, the solution separates into two immiscible liquid phases in equilibrium. The top layer is water-rich and the bottom layer is paraben-rich. The area in the ternary phase diagram of the liquid-liquid-phase separation region increases with increasing temperature. The area of the liquid-liquid-phase separation region decreases from butyl paraben, propyl paraben to ethyl paraben at the constant temperature. Cooling crystallization of solutions of different proportions of butyl paraben, water and ethanol have been carried out and recorded using the Focused Beam Reflectance Method, Particle Vision and Measurement, and in-situ Infrared Spectroscopy. The FBRM and IR curves and the PVM photos track the appearance of liquid-liquid phase separation and crystallization. The results suggest that the liquid-liquid phase separation has a negative influence on the crystal size distribution. The work illustrates how Process Analytical Technology (PAT) can be used to increase the understanding of complex crystallizations. By cooling crystallization of butyl paraben under conditions of liquid-liquid-phase separation, crystals consisting of a porous layer in between two solid layers have been produced. The outer layers are transparent and compact while the middle layer is full of pores. The thickness of the porous layer can reach more than half of the whole crystal. These sandwich crystals contain only one polymorph as determined by Confocal Raman Microscopy and single crystal X-Ray Diffraction. However, the middle layer material melts at lower temperature than outer layer material. / <p>QC 20130515</p> / investigate nucleation and crystallization of drug-like organic molecules