Ce doctorat portait sur le développement de nanoparticules (NPs) photosensibles constituées d’un cœur photolysablepoly(acrylate d'o-nitrobenzyle) (polymère hydrophobe biocompatible - PANB) et d’une couronne basée sur un dérivé du dextrane (polysaccharide bactérien, hydrophile et biodégradable). Dans un premier temps, le PANB-N3 a été synthétisé par i) polymérisation radicalaire contrôlée (SET-LRP) de l’acrylate d’o-nitrobenzyle puis ii) modification chimique de l’extrémité de chaîne par une fonction azoture. En parallèle, le dextrane a été hydrophobisé par quelques chaînes grasses dotées d’un groupe alcyne (obtention du DexAlcyne-15). Ces polymères précurseurs peuvent alors réagir par chimie click CuAAC (Cycloaddition azide-alcyne catalysée par Cu(I)) pour engendrer divers glycopolymères greffés Dex-g-PANB. Dans un deuxième temps, les NPs ont été formulées par deux procédés puis caractérisées en termes de taille, recouvrement en dextrane (quantité par gramme de PANB, épaisseur de la couche surfacique) et stabilité colloïdale en milieu salin, en présence de tensioactif compétitif ou dans un milieu de culture (DMEM). Le procédé de nanoprécipitation a été appliqué aux Dex-g-PANB présentant de fortes fractions massiques en PANB (>40%) alors que le procédé d’émulsion-évaporation de solvant organique a été mis en œuvre en utilisant le DexAlcyne-15 comme tensioactif hydrosoluble et le PANB-N3 comme matériau hydrophobe. Grâce à leurs fonctionnalités complémentaires, une réaction CuAAC peut (ou non) avoir lieu à l’interface liquide/liquide pendant l’élaboration des NPs et conduire à l’obtention de NPs « non clickées » ou « clickées ». Enfin, le caractère photosensible des NPs a été validé par irradiation UV en observant une disparition progressive des NPs résultant de la photolyse des PANB. Afin d’utiliser ces NPs comme systèmes stimulables de délivrance de médicaments, un anticancéreux (Doxorubicine - Dox) a été encapsulé au sein des NPs, pendant leur élaboration. Cette encapsulation a été optimisée et les NPs chargées de DOX ont été caractérisées en termes de taille et d’efficacité d’encapsulation. La libération de la DOX hors des NPs a ensuite été suivie par simple diffusion, ou provoquéepar irradiation UV. Enfin, le potentiel biologique de ces NPs a été évalué vis-à-vis d’une lignée cellulaire tumorale humaine d'origine intestinale isolée d'un adénocarcinome colique (Caco-2). Après vérification de leur biocompatibilité et de la résistance des Caco-2 aux irradiations UV, nous avons pu montrer que les NPs chargées pouvaient libérer suffisamment de DOX en seulement 30 secondes d’irradiation (puissane: 54mW/cm2) pour éradiquer plus de 50% de ces cellules cancéreuses. / This work was focused on the development of light-sensitive nanoparticles (NPs) based on a photodegradable poly(o-nitrobenzyl acrylate) core(PNBA, hydrophobic and biocompatible polymer) and a dextran derivative shell (dextran is a biodegradable and hydrophilic bacterial polysaccharide). Firstly, PNBA-N3 was synthesized by i) Single-Electron Transfer Living Radical Polymerization (SET-LRP) of o-nitrobenzyl acrylate then ii) introduction of one azide end-function. In the same time, DexAlkyne-15 carrying several alkyne groups was produced by hydrophobization of dextran. Such DexAlkyne-15 and PNBA-N3 can react by CuAAC (Cu(I)-catalyzed azide-alkyne cycloaddition) click chemistry leading to Dex-g-PNBA glycopolymers with various macromolecular parameters. Secondly, NPs were produced by comparing two processes then characterized in terms of size, dextran amount, shell thickness and colloidal stability in NaCl or cell culture media, or in presence of one strong surfactant. On one hand, NPs were made by nanoprecipitation of Dex-g-PNBA exhibiting high PNBA weight fractions (>40 %). On the other hand, NPs were produced by emulsion-evaporation of the organic solvent using DexAlkyne-15 as water-soluble surfactant and PNBA-N3 as hydrophobic materials. In this case, in situ CuAAC occurred (or not) at the liquid/liquid interface during the NPs formulation, leading to “clicked” and “not-clicked” NPs. Finally, NPs disruption was studied by UV irradiation according the PNBA chains photolysis. To use such NPs as smart drug delivery systems, Doxorubicin (DOX - an anticancer agent), was loaded inside the NPs during their elaboration. The experimental conditions were optimized to enhance the DOX encapsulation. The kinetics release of encapsulated DOX were studied by diffusion or under UV irradiation. Finally, the biological potential of these NPs was estimated towards Caco-2 (continuous line of heterogeneous human epithelial colorectal adenocarcinoma cells). After checking the NPs biocompatibility and theCaco-2 strength under UV irradiation, we proved that such loaded NPs can release enough DOX under 30 second irradiation (power: 54mW/cm2) to decrease the Caco-2 viability about more than 50%.

La présente étude a été consacrée à l'étude du potentiel du PDMS pour l'élaboration d'un procédé de séparation membranaire à sélectivité variable et contrôlée. La nanofiltration se base une théorie relativement jeune. Les mécanismes impliqués dans les performances des membranes sont encore sujet à controverse au vu des données de la littérature. La caractérisation du gonflement solvo-dépendant du polymère, ainsi que de ses propriétés de compressibilité à l'état gonflé, ont permis de relier directement les propriétés de perméation et de tamisage moléculaire d'une membrane de PDMS à son état physico-chimique. L'étude de l'influence des paramètres opératoires a dans un premier temps permis d'apporter des éléments de compréhension significatifs concernant les propriétés de perméation résultant de la variabilité de l'agencement structural et géométrique du réseau polymérique. Degré de gonflement, compressibilité de la membrane lorsque soumise à la pression transmembranaire, affinités solvant/membrane et viscosité du solvant ont été mise en avant pour décrire le flux de solvant à travers la membrane. Au vu des résultats, ce dernier résulterait davantage d'un transport de type hydraulique à travers les interstices du PDMS gonflé, qui se comporte analogiquement à un système poreux dans cet état. Les mécanismes de transport impliqués ont pu être confirmés et agrémentés au cours d'une étude de la rétention de molécules modèles : les polyéthylèneglycols. Il a alors été montré, via l'étude de leur rétention individuelle, la faisabilité d'un procédé membranaire dont les performances sont variables et peuvent être ciblés par un choix adéquat des conditions opératoires. Deux types majeures d'influences ont alors pu être soulignée : celles liées à la structure du système solvant/PDMS et celles attribuées aux propriétés physico-chimique de la solution à traiter, présentant des effets synergique pour certains d'entre eux. Après avoir démontré la flexibilité contrôlée des performances de filtration, l'application du système de NF a été concrétisée par l'étude de la purification et du fractionnement de peptides : une purification d'un milieu issu d'une synthèse par voie chimique (un hydrazynopeptide) et le fractionnement ciblé d'un hydrolysat de protéines en provenance de ressources agroalimentaires. Cette étude prospective a alors permis de conclure à de prometteuses capacités du système de NF pour la mise en oeuvre de séparations membranaire dont la sélectivité et la productivité peut être appréhendée et ciblée par des conditions opératoires adaptées / The present study aimed to study the ability to build an adaptative and controlled separation process using PDMS membranes for organic solvent nanofiltration (OSN). Despite the well understanding of mechanisms implied in the performances of nanofiltration in aqueous media, the ones conditioning OSN productivity and sieving properties remains unclear. The characterization of the PDMS swelling when put in contact with several solvent and submitted under pressure allowed for correlating the structural conformation of the PDMS membrane to its permeation properties. The study of the influence of different operating parameters on the solvent fluxes has brought significant insights in the understanding of permeation mechanisms. Swelling degree (SL), membrane compressibility under transmembrane pressure (TMP), solvent/membrane affinity and solvent viscosity were pointed out as major parameters governing the filtration through PDMS membranes. The results concluded on a molecular transport attributed to hydraulic transport through the swollen PDMS, which behavior in this state was similar to a porous material. The transport mechanisms were confirmed and deepened with a study of solute retention using homologous series of polyethylenglycols as « model » molecules. The results have shown the ability to build a separation process with targeted performances when using the appropriate operating conditions (TMP, SL, temperature...). Two main categories of impact were shown to condition the selectivity and the productivity of the membrane: the ones attributed to the polymer/solvent layout and the ones concerning the physico-chemical properties of the filtrated solution. Both categories have in addition presented synergetic effects on the process performances. After the demonstration of the ability to vary and control the sieving properties of the PDMS membranes, the nanofiltration system was applied to two concrete case studies: a purification of a hydrazynopeptide after its production via a chemical synthesis and a fractionation of a protein hydrolyzate originating from renewable resources. In both cases, the prospection of the PDMS ability in terms of targeted selectivity and productivity showed interesting results that confirmed a promising development of a separation process among the sieving properties can be regulated by the application of suitable operating conditions

L’objectif de cette étude était d’améliorer les performances de séparation OSN de membranes commerciales en vue d’applications en métathèse dans laquelle des catalyseurs hautement dilués sont utilisés. Dans ce travail, des membranes polymères commerciales ont d'abord été étudiée pour caractériser leurs performances dans des milieux organiques en utilisant des mélanges binaires très dilués solute-solvant. Sur la base d'une revue de la littérature, il a été montré que la membrane PERVAP4060, dont le PDMS est la couche active dense était un candidat prometteur pour la nanofiltration milieu organique (OSN). En tant que membrane poreuse, les supports commerciaux AMS et PAN ont également été pris en compte. Dans cette étude, nous avons considéré la modification sur la surface pour conserver les propriétés de matrice polymère. Les multicouches de plasma Ar/O2 et/ou de polyélectrolytes ont été utilisées pour la préparation de membranes prototypes. Les membranes non modifiées et modifiées ont été testées dans des conditions OSN en utilisant des mélanges d'alimentation biniares. Plusieurs solutés très dilués, le ligand organophosphoré R-BINAP, un catalyseur de transfert de phase (ToABR) et des alcanes linéaires ont été étudiés. Le R-BINAP et le ToABR ont tous deux été utilisés dans la plage de 0,0001 à 0,5% en masse et la plupart des expériences ont été réalisées ensuite avec des concentrations de 0,05% en masse de soluté dans le toluène. Il a été montré que le PDMS était capable de retenir 80% de R-BINAP et environ 93% de ToABr dans du toluène. Après modification par les dépôt LBL, le taux de rejet est amélioré avec les membranes modifiées PERVAP4060, conduisant à une rétention de 88% du R-BINAP avec un dépôt de 10 bicouches de polyélectrolytes PAH / PSS en surface, ce taux de rejet pouvant atteindre 95% lorsque le nombre de bicouches est de 20. Le taux de rejet de ToABr augmente à 97%. Les performances de la membrane ont été étudiées sous différentes pressions comprises entre 1 et 40 bars; le haut rejet, encore observé dans ces conditions OSN, plaide résolument en faveur d'un mécanisme de transfert de type solution-diffusion à travers le PDMS. On a également étudié le traitement des mélanges ternaires mimant le mélange catalyseur / solutés / solvant, correspondant à l'hydroformylation ; aucun signe de couplage n’a été détectée et le taux rejet du soluté de masse molaire la plus forte est resté inchangé. D'autre part, l'amélioration du taux de rejet a également observée à partir des membranes poreuses après modification. Le taux de rétention du C44 dans l'AMS a été atteint 75% après modification par 10 bicouches de PDDA / PSS, alors qu’il n'était que de 25% avant modification. Dans le PAN modifié, le taux de rejet des solutés obtenus est dans la plage de 37 à 50%, alors qu’il n'était que de 3 à 7% en masse avant modification. L'inconvénient de la membrane poreuse est toutefois la forte diminution du flux après le dépôt des couches multiples. / The objective of this study was to improve the OSN separation performance of commercial membranes for metathesis applications in which highly diluted catalysts are used. In this work, commercial polymeric membranes were first studied to characterize their performance in organic media using very dilute solute-solvent binary mixtures. Based on a literature review, it was shown that the PERVAP4060 membrane, of which PDMS is the dense active layer, was a promising candidate for organic solvent nanofiltration (OSN). As a porous membrane, the AMS and PAN commercial supports have also been taken into account. In this study, we considered the modification on the surface to improve the separation properties of polymeric OSN membranes. Ar/O2 plasma and/or polyelectrolytes multilayers were used for the preparation of new prototype membranes. Unmodified and modified membranes were tested under OSN conditions using binary feed mixtures. Several highly dilute solutes, organophosphorus ligand R-BINAP, phase transfer catalyst ToABR, and linear alkanes have been studied. Both R-BINAP and ToABR were used in the range of 0.0001 to 0.5% by weight, and most experiments were subsequently performed with 0.05% solute concentrations in toluene. It has been shown that PDMS can retain 80% R-BINAP and about 93% ToABr in toluene. After modification by the LBL deposition, the rejection is improved with the modified PERVAP4060 membranes, leading to an 88% rejection of R-BINAP with a deposit of 10 PAH / PSS polyelectrolyte bilayers at the surface and this rejection being able to reach 95% when the number of bilayers is 20. ToABr rejection increases to 97% with the ten bilayered membranes. The performance of the membrane was studied under different pressures of between 1 and 40 bar; the high rejection, still observed in these OSN conditions, strongly supports a solution-diffusion transfer mechanism through the PDMS. The treatment of ternary mixtures mimicking the catalyst/solute/ solvent mixture corresponding to the hydroformylation has also been studied; no evidence of coupling was detected, and the highest retention remained unchanged. On the other hand, the improvement of the rejection also observed from the porous membranes after modification. The rejection of C44 in the AMS was reached 75% after modification by tention10 bilayers of PDDA / PSS, whereas it was only 25% before modification. In the modified PAN, the rejection of the solutes obtained is in the range of 37 to 50%, whereas it was only 3 to 7% by weight before modification. The disadvantage of the porous membrane, however, is the sharp decrease in flux after the deposition of the multiple layers.

105 f. / Submitted by Ana Hilda Fonseca (anahilda@ufba.br) on 2013-10-03T13:45:39Z No. of bitstreams: 1 Apresentação_Denise_VersãoFinal.pdf: 4275455 bytes, checksum: 65d7b6e55b90b2695016ec5154b6bbc4 (MD5) / Approved for entry into archive by Ana Hilda Fonseca(anahilda@ufba.br) on 2013-10-03T13:48:30Z (GMT) No. of bitstreams: 1 Apresentação_Denise_VersãoFinal.pdf: 4275455 bytes, checksum: 65d7b6e55b90b2695016ec5154b6bbc4 (MD5) / Made available in DSpace on 2013-10-03T13:48:30Z (GMT). No. of bitstreams: 1 Apresentação_Denise_VersãoFinal.pdf: 4275455 bytes, checksum: 65d7b6e55b90b2695016ec5154b6bbc4 (MD5) Previous issue date: 2012 / A espectroscopia na região do infravermelho próximo (NIRS), associada a técnicas quimiométricas, foi utilizada no desenvolvimento de modelos de calibração multivariada para a predição da composição química de um solvente orgânico- aquoso utilizado na produção de isopreno. Os modelos foram construídos para a predição da concentração dos componentes presentes no solvente: acetona, acetonitrila, água, n-propanol, i-propanol, álcool alílico, t-butanol e DCPD (diciclopentadieno-1,3). Uma análise exploratória dos dados foi realizada para detecção de amostras anômalas, através da análise de componentes principais (PCA). Para seleção dos conjuntos de calibração e validação, o algoritmo SPXY (Sample set Partitioning based on joint x-y distances) foi utilizado. As condições experimentais para a construção dos modelos foram escolhidas através da realização de um planejamento experimental para três variáveis baseado na matriz Doehlert, em que foram estudadas 1) técnica de pré-processamento, 2) faixa de comprimento de onda, obtidas através do algoritmo de seleção de variáveis por regressão dos mínimos quadrados parciais por intervalo (iPLS), e 3) seleção de variáveis espectrais, com a utilização do algoritmo Jack Knife. A técnica de regressão por mínimos quadrados parciais (PLS) foi utilizada para a calibração multivariada. As variáveis de resposta, PC, RMSECV, r2regr, RMSEP, r2valid, Slope Valid e pvalue, obtidas a partir dos modelos definidos no planejamento experimental, foram otimizadas simultaneamente, através da função de desejabilidade. Novos modelos de calibração foram construídos a partir dos valores ótimos encontrados para cada variável de entrada. Pelo menos 85 amostras de calibração foram usadas em cada modelo, sendo necessários entre 1 e 10 fatores para assegurar o melhor desempenho de cada modelo. Os coeficientes de determinação de validação cruzada (r2regr) foram maiores que 0,92 para todas as propriedades. Os valores para os RMSEPs variaram de 0,39 a 1,66 (% m/m). Portanto, o método desenvolvido mostrou-se viável para determinação da composição química do solvente e auxiliar no controle do processo da unidade de produção de isopreno. / Salvador

The integration of organic solvent nanofiltration in processes of fine chemistry involving homogeneous metal catalysts has a great potentiel because this eco-friendly process, efficient at molecular scale, does not desactivate the catalyst contrary to conventionnal distillation. The aim of this study is to integrate organic solvent nanofiltration in the process of 10-undecenitrile hydroformylation in toluene. A one-step nanofiltration does not permit to fulfill the goals of the separation, which are to extract the product and to recycle the catalytic system (Rh, biphephos). Simulations of membrane cascades based on experimental data of flux and retention according to the concentration (acquired in the first part of the thesis) highlighted that a four stages cascades with recycling is realistic and competitive for an industrial plant. / L'intégration de la nanofiltration organique dans les procédés de chimie fine impliquant des catalyseurs organométalliques solubles a un fort potentiel car ce procédé éco-efficace de séparation à l'échelle moléculaire ne désactive pas les catalyseurs contrairement à la distillation classiquement utilisée. L'objectif de cette thèse est d'intégrer la nanofiltration organique dans le procédé d'hydroformylation du 10-undecenitrile dans le toluène. Un procédé en une étape de nanofiltration ne permet pas de remplir les objectifs de séparation qui sont l'extraction du produit et le recyclage du système catalytique (Rh, biphephos). Des simulations de cascades de membranes basées sur les données expérimentales de flux et de rétentions variables en fonction de la concentration, acquises en première partie de thèse, ont permis d'identifier un design de cascade à 4 étages avec recyclages réaliste et compétitif pour une conception industrielle.

Among the next generation materials being investigated for membrane development, partially reduced Graphene Oxide (rGO) has received increasing attention from the membrane community. rGO-based nanofiltration membranes have shown promising results in applications such as partial desalination, organic contaminant removal, gas-phase separations, and separations from solvent media. rGO offers a unique platform compared to common polymeric membranes since it can be used for separation applications in both aqueous and organic solvent media. An rGO-based platform could also be utilized to synthesize reactive membranes, giving rGO membranes the additional capability of reactively removing organic contaminants. This research focuses on the synthesis of rGO and nanocomposite membranes for applications including the separation of high-value phenolic compounds from a solvent-water mixture, removal of organic contaminants, and treatment of refinery wastewater. First, the behavior of a rGO membrane in water and isopropanol was investigated along with its ability to separate high-value, lignin-derived oligomeric compounds from a solvent-water mixture. This study revealed the formation of stable sorbates of water in the GO channels that resulted in declined membrane permeance and improved size-exclusion cutoff. Through controlled reduction of GO by heat treatment, it was demonstrated that physicochemical properties of the GO membrane could be modulated and separation performance tuned based on the extent of reduction. A varying degree of interlayer spacing was attained between the GO laminates by controlling the O/C ratio of GO. This allowed the rGO membrane to achieve tunable molecular separation of lignin-derived model oligomeric compounds from a solvent-water mixture. Second, the mechanism of ionic transport through the rGO membrane was studied as well as its application in partial desalination and removal of persistent organic contaminants from water. Through comprehensive experimental investigations and mathematical analysis, along with the aid of the extended Nernst Planck equation, the impacts of steric hindrance and charge interactions on the underlying ion transport mechanism were quantified. Charge interactions were observed to be the dominant exclusion mechanism for the rGO membranes. The application of rGO membranes for treatment of high TDS produced water was investigated with the goal of partial hardness and dissolved oil removal. In addition, this study demonstrated the removal of emerging organic contaminants, specifically perfluorooctanoic acid, by rGO membranes and elucidated a charge interaction-dominated exclusion mechanism for this contaminant, as well. Finally, rGO-based and microporous polyvinylidene fluoride (PVDF)-based catalytic membrane platforms were synthesized for removal of organic contaminants via an oxidative pathway. Herein, an advanced oxidation process was integrated with membrane technology by the in-situ synthesis of Fe-based nanoparticles. The unique capability to oxidatively remove contaminants in a continuous mode of operation was explored in addition to the separation performance of the membrane. The rGO-based platform achieved high oxidative removal of trichloroethylene via a sulfate-free, radical-mediated pathway, while simultaneously removing humic acids from water and potentially eliminating undesired side reactions. A PVDF-based microporous catalytic membrane platform was shown to effectively remove organic impurities, such as Naphthenic acids, from high TDS produced water by the same pathway. The enhancement of reaction extent for elevated temperatures and longer residence times was also quantified in this study. These studies benefit the membrane community in the following ways: 1) The work identifies the critical role of the physicochemical properties of GO, such as the O/C ratio and water sorption, for determining the permeability-selectivity of rGO membranes for solvent nanofiltration. 2) Investigations of ion transport through rGO membranes led to an understanding of a charge-dominated separation mechanism for ion retention. The Nernst-Planck equation-based approach employed in this study would enable further assessment and comparison of rGO membranes under a wide set of parameters. 3) Catalytic membrane platforms (rGO and microporous PVDF-based) were synthesized for conducting advanced oxidation reactions in the porous membrane domain, demonstrating potential applications in environmental remediation of organic contaminants.

Membrane technology has great potential to complement traditional energy-intensive molecular separation processes such as distillation, with the advantage of low footprint generation. However, this would only be achieved with the development of better membranes able to operate in challenging conditions, including combinations of organic solvents, high temperatures, extreme pHs, and oxidative environments. This dissertation aims to use high-performance polymeric materials that can withstand temperatures of 120 °C in polar aprotic solvents like N,N-dimethylformamide as separation membranes, using different crosslinking strategies and alternative routes for commercially available material processing. The thesis will be divided into two main approaches. The first approach will start from soluble polyimides as precursors, with designed functionalities that allow post-membrane modifications, such as chemical crosslinking, thermal crosslinking, and thermal rearrangement to enhance the material's chemical resistance. The focus will be on the polyimide synthesis by an alternative one-step room-temperature polyhydroxyalkylation reaction. The chemical and thermal crosslinking take place without involving the imide bond, by incorporating a highly tunable functional group (isatin) in the synthesis of the materials. Propargyl as a pendant group will be used for the thermal crosslinking, and hydroxyl group for the thermal rearrangement. In all cases, the obtained membranes were stable in common organic solvents at 120 °C. The second approach will start from intrinsically solvent-resistant and commercially available poly(aryl ether ketone)s, turned into membranes by a closed-loop modification-regeneration strategy, to address long-term separations in organic solvents at high temperatures. We present for the first time porous poly(aryl ether ketone) flat-sheet and hollow fiber membranes prepared without the use of strong acids or high temperatures. Two methodologies are proposed. The developed strategies shall contribute toward avoiding the regular consumption of new materials and waste generation since the polymer used does not require crosslinking for its stability under organic solvents.

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.

Nesse trabalho utilizou-se o reator anaeróbio horizontal de leito fixo (RAHLF) para produção de ácidos graxos voláteis (AGVs). O reator, com volume total de 2,38 litros, foi preenchido com partículas de argila expandida e alimentado com substrato sintético à base de glicose. Com concentração de glicose de 2000 mg/L, sem adição de alcalinizante e com tempo de detenção hidráulica (TDH) de 2 horas, houve produção de ácidos acético, butírico e propiônico. Com a variação do (TDH) de 2 horas para 0,5 hora, em condições idênticas, houve redução da produção do ácido butírico. Na segunda condição testada, em que a concentração da glicose foi 4000 mg/L, a concentração dos três ácidos aumentou, além de ser produzido o ácido capróico. Nas três últimas experimentações, com a glicose a 2000 mg/L e alcalinizada com bicarbonato de sódio, nas concentrações de 0,1000 e 2000 mg/L e TDH em 0,5 hora, as produções do ácido acético e propiônico aumentaram, enquanto que houve diminuição da produção dos ácidos butírico e capróico. A extração dos AGVs foi realizada em coluna de 320 mL de leito, com resina de troca iônica Dowex Marathon A - tipo aniônica base forte de amina quaternária em gel de divinil benzeno-estireno como matriz. O primeiro sistema extratante testado, foi com a resina condicionada na forma \'CL POT. -\' e a eluição foi feita com solução de \'NA\'\'CL\' em várias concentrações. Os percolados apresentaram alto teor de cloreto, inconveniente para as recuperações dos AGVs ou para o seu descarte no ambiente. O sistema testado com a resina condicionada na forma \'OH POT.-\' e a eluição com solução de \'NA\'\'OH\', em pH 13,5, demonstrou ser viável para a extração e concentração dos AGVs, com os fatores de concentração acima de 25, além de 80% do volume do percolado da fixação ser adequado para a devolução ao ambiente. No último teste o sistema utilizado foi o mesmo, com a alimentação apresentando a relação AVTs : sulfato de 1:1,27 e procurou-se fixar a máxima quantidade de AVTs. A eluição foi com solução de \'NA\'\'OH\' em três diferentes valores de pH: 12, 12,5 e 13. A presença do sulfato, nessa relação, dificultou a fixação dos AVs e, na eluição, competiu com os AVs, resultando em baixos fatores de concentração entre 2 e 3. Um volume de 47% do percolado da fixação e outro, de 29% da eluição, apresentou qualidade para o descarte. Na extração com solvente foram testados dois extratantes, a Alamina 336 (tri-octil/decil amina) e a Alamina 304-1 (tri-n-dodecilamina). O melhor sistema extratante, de solução de AVs impurificada com alto teor de sulfato, foi com a Alamina 336 condicionada com ácido nítrico. Entretanto, o consumo do ácido é alto o suficiente para inviabilizar economicamente a extração. Extração em sistema com baixo teor em sulfato e pH igual a 4,0 demonstrou ser técnicamente viável. Todavia, os valores da DQO residual nos refinados aquosos de todos os sistemas impossibilitam a devolução direta ao ambiente. / This work used the horizontal-flow anaerobic immobilized biomass (HAIB) reactor in order to produce volatile fatty acids (VFAs). The reactor, filled up with expanded clay particles, had a total volume of 2,38 liters and was fed with glucose based synthetic substrate. Production of acetic, butyric, and propionic acids occurred at an influent glucose concentration of 2000 mg/L without any addition of buffer agent and at a hydraulic retention time (HRT) of 2 hours. A reduction in butyric acid production occurred with the decrease of the HRT from 2 to 0,5 hours, with the reactor operating in identical conditions. In a second test condition, where the influent glucose concentration was increased to 4000 mg/L, the production of the three acids increased, beside the production of caproic acid. In the last three experiments, with influent glucose concentration at 2000 mg/L and buffered with sodium bicarbonate at concentrations of 0,1000 e 2000 mg/L and HRT of 0,5 hours, the production of acetic and propionic acids increased, whereas the production of butyric and caproic acids decreased. VFA extraction was accomplished in a 320 mL bed containing the ionic exchange resin Dowex Marathon A - strong base anionic type of quaternary amine in gel of benzene-styrene divinyl as matrix. The first extractant system was tested with the resin conditioned as \'C L POT.-\' and the elution was done with a solution of \'NA\'\'CL\' at different concentrations. The percolates presented high chloride concentration, which is inconvenient for the recovery of VFA or their release to the environment. On the other hand, the system with resin conditioned as \'OH POT.-\' and the elution with a solution of \'NA\'\'OH\' at pH 13,5 showed to be a viable option for the extraction and concentration of VFA with concentration factors above 25. In addition, the 80% of the volume of the fixation percolate is suitable for the devolution into the environment. The same system was used in the last test, however with the feeding at total volatile acids (TVA): sulfate ratios of 1:1,27 trying to fix the maximal amount of TVAs. The elution was done with \'NA\'\'OH\' at three different pH values: 12, 12,5 and 13. The presence of sulfate at this ration hampered the fixation of the volatile acids (VA) and during the elution competed with the VA, resulting in low concentration factors between 2 and 3. The volume of 47% of the fixation percolate and the volume of 29% of the elution presented good quality for discharge. Two extractants were tested in the extraction tests with solvents: Alamine 336 (tri-octyl/decyl amine) and the Alamine 304-1 (tri-n-dodecylamine). The best extractant system for the VA contaminated with high concentrations of sulfate was the Alamine 336 conditioned with nitric acid. The consumption of acid, however, was high enough to make the extraction economically unfeasible. On the other hand, extractions in systems with low sulfate concentrations and pH of 4 showed to be technically feasible, even though the residual chemical oxygen demand (COD) in the aqueous refined of all systems was too high for their direct devolution to the environment.

Ein Spezialgebiet der modernen Mikroelektronik ist die Miniaturisierung und Entwicklung von neuen nanostrukturierten und Komposit-Materialen aus 3d-Metallen. Durch geeignete Zusammensetzungen können diese sowohl mit einer hohen Sättigungsmagnetisierung und Koerzitivfeldstärke als mit besserer Oxidationsbeständigkeit im Vergleich zu den reinen Elementen erzielt werden.<br /> <br /> In der vorliegenden Arbeit werden neue Methoden für die Herstellung von bimetallischen kolloidalen Nanopartikeln vor allem mit einer Kern-Hülle-Struktur (Kern@Hülle) präsentiert. Bei der überwiegenden Zahl der vorgestellten Reaktionen handelt es sich um die thermische Zersetzung von metallorganischen Verbindungen wie Kobaltcarbonyl, Palladium- und Platinacetylacetonate oder die chemische Reduktion von Metallsalze mit langkettigem Alkohol in organischem Lösungsmittel. Daneben sind auch Kombinationen aus diesen beiden Verfahren beschrieben. Es wurden Kolloide aus einem reinen Edelmetall (Pt, Pd, Ag) in einem organischen Lösungsmittel synthetisiert und daraus neue, bisher in dieser Form nicht bekannte Ag@Co-, Pt@Co-, Pd@Co- und Pt@Pd@Co-Nanopartikel gewonnen.<br /> <br /> Der Kobaltgehalt der Ag@Co-, Teilchen konnte im Bereich von 5 bis 73 At. % beliebig eingestellt werden. Der mittlere Durchmesser der Ag@Co-Partikel wurde von 5 nm bis 15 nm variiert. Bei der Herstellung von Pt@Co-Teilchen wurde eine unterschiedlich dicke Kobalt-Hülle von ca. 1,0 bis 2,5 nm erzielt. Im Fall des Palladiums wurden sowohl monodispere als auch polydisperse Pd-Nanopartikel mit einer maximal 1,7-2,0nm dicken Kobalthülle synthetisiert.<br /> <br /> Ein großer Teil dieser Arbeit befasst sich mit den magnetischen Eigenschaften der kolloidalen Teilchen, wobei die SQUID-Magnetometrie und Röntgenzirkulardichroismus (XMCD) dafür eingesetzt wurden. Weil magnetische Messungen alleine nur indirekte Schlüsse über die untersuchten Systeme erlauben, wurde dabei besonderer Wert auf die möglichst genaue strukturelle Charakterisierung der Proben mittels moderner Untersuchungsmethoden gelegt. Röntgendiffraktometrie (XRD), Röntgenabsorptionsfeinstruktur- (EXAFS) und UV-Vis-Spektroskopie sowie Transmissionselektronenmikroskopie (TEM) in Kombination mit Elektronen Energieverlustspektroskopie (EELS) und energiedispersive Röntgenfluoreszensanalyse (EDX) wurden verwendet. / Magnetic colloidal particles are attractive because of their possible application to ultra-high-density magnetic data storage media, sensors, electronic devices and medical diagnostics. The properties of small particles depend on their composition, shape, and method of preparation. The combination of 3d-metals (Fe, Co, Ni) with noble metals improves the stability of the colloids and leads to new properties of the magnetic systems, often distinct from those of the corresponding monometallic particles. Core-shell particles, where dia- or paramagnetic noble metal-cores are surrounded by a ferromagnetic Co-shell, are an interesting system to study surface and interfacial magnetism such as an induced polarization or a giant magnetoresistance effect. <br /> <br /> In this work, new synthetic routes for the preparation of monometallic (Pt, Pd, Ag) and bimetallic magnetic nanocrystals (Ag@Co, Pt@Co, Pd@Co) with core-shell structure are presented. Stable colloids with a narrow particle size distribution were obtained in organic solvents using methods of wet chemistry. The method of preparation of Ag@Co is based on the thermal decomposition of dicobalt octycarbonyl in combination with a transmetalation reaction with water free AgClO4. The cobalt amount in the Ag@Co system could be tuned from 5 to 73 at. %. The average diameter of the particles was varied from 5 to 15 nm. <br /> <br /> The reduction of platinum and palladium salts in organic solution using long chained alcohol as the reductant leads to stable metal nanostructures. Monodisperse Pd and Pt particles with average sizes of 1.7 to 7.0 nm were synthesized via thermal decomposition of metal-surfactant complexes too. Alkylamines and alkylphosphines were used in this procedure. The thickness of the Co-shell was controlled by a simple high-temperature thermolysis of dicobalt octacarbonyl at the presence of Pd and Pt seeds and was tunable from 0.5 to 2.5 nm. <br /> <br /> The crystalline structure of the samples was characterized by transmission electron microscopy (TEM), energy dispersive x-ray spectroscopy (EDX), UV-VIS and electron-energy loss spectroscopy (EELS). SQUID magnetometry, x-ray magnetic circular dichroism (XMCD) and extended x-ray absorption fine structure (EXAFS) measurements gave information about the magnetic properties of the bimetallic systems and revealed their dependency on the particle size and the chemical composition. A high spin to orbital moments ratio µL/µS of 0.26±0.06 for Ag@Co and 0.22±0.05 for Pt@Co nanocrystals was observed at XMCD measurements due to the lowered dimensionality the investigated systems.