Polymer foams belong to the solid foams family which are versatile materials, extensively used for a large number of applications such as automotive, packaging, sport products, thermal and acoustic insulators, tissue engineering or liquid absorbents. Composed of air bubbles entrapped in a continuous solid network, they combine the properties of the polymer with those of the foam to create an intriguing and complex material. Incorporating a foam into a polymer network not only allows one to use the wide range of interesting properties that the polymer offers, but also permits to profit from the advantageous properties of foam including lightness, low density, compressibility and high surface-to-volume ratio. Generally, the properties of polymer foams are strongly related to their density and their structure (bubble size and size distribution, bubble arrangement, open vs closed cells). Having a good control over foam properties is thus achieved by first controlling its density and structure.We developed a technique in which solid foams are generated essentially in a two-step process: a sufficiently stable liquid foam with well-controlled structural properties is generated in a first step, and then solidified in a second one. With such a two-step approach, the generation of solid foams can be divided into a number of well-separated sub-tasks which can be controlled and optimised separately. The transition from liquid to solid state is a sensitive issue of a great importance and therefore needs to be controlled with sufficient accuracy. It is essentially composed of three key steps: foam generation, mixing of reactants and foam solidification and requires the optimisation of foam stability in conjunction with an appropriate choice of both foaming time and solidification time. Furthermore, a good homogeneity of the polymer foam calls for a good mixing of the different reactants involved in the foaming and the polymerisation.A particularly powerful demonstration of the advantages of this approach is given by solidifying monodisperse liquid foams generated using millifluidic technique, in which all bubbles have the same size. In a liquid foam, equal-volume bubbles self-order into periodic, close-packed structures under gravity or confinement. As such, monodisperse foams provide simultaneous control over the size and the organisation of the pores in the final solid with an accuracy which is expected to give rise to a better understanding of the structure-property relationship of porous solids and to the development of new porous materials.We therefore aim to explore the new spectrum of properties, which polymer foams offer when we introduce an ordered structure into them since the most widely used polymer foams nowadays have disordered structures. The goal of our study is to demonstrate the feasibility of this two-step approach for different classes of polymers, including biomolecular hydrogel, superabsorbent polymer and polyurethane.For the generation of the structured polymer foams we use Lab-on-a-Chip technologies which allow the "shrinking" of large-scale set-ups to micro/millimetic scale. It permits also to perform "flow chemistry" in which the various liquid and gaseous ingredients of the foam are injected and mixed in a purpose-designed network of the micro- and millifluidic Lab-on-a-Chip. We adjust this approach according to the requirements of each polymer system, i.e. the foaming and the mixing techniques are chosen to fit the properties of each system, and can be exchanged to fit the properties of the studied systems.

Myo-inositol is ubiquitous in nature and is found at the structural core of a diverse range of biologically important derivatives, including phosphatidylinositols, inositol phosphates and mycothiol. The synthesis of myo-inositol derivatives is notoriously difficult due to the need to control both regio- and enantioselectivity. As a result, synthetic routes to derivatives of this type are often lengthy and low yielding. The first biosynthetic step in the production of all myo-inositol metabolites is the isomerisation of D-glucose 6- phosphate to L-myo-inositol 1-phosphate as mediated by L-myo-inositol 1-phosphate synthase (INO1). For the protozoan parasite Trypanosoma brucei, INO1 is essential for survival and its version of the enzyme (TbINO1) has a high turnover. This makes TbINO1 an attractive candidate for the biocatalytic production of L-myo-inositol 1- phosphate, and a potential starting point for drastically shortened syntheses of important myo-inositol derivatives. The production of L-myo-inositol 1-phosphate by TbINO1 has been optimised to achieve complete conversion in reaction conditions that facilitate product isolation. Due to problems with an in-batch process, the TbINO1 enzyme was immobilised and the process was transferred to a flow system. This has allowed for production of significant quantities of L-myo-inositol 1-phosphate with a high level of purity. L-myo-inositol 1- phosphate obtained from the flow system has been used to prepare mycothiol glycosylation acceptor, 1,2,4,5,6-penta-O-acetyl-D-myo-inositol, in a concise synthesis with a greatly improved yield over the literature.

Les protéoglycanes sont des macromolécules composées de glycosaminoglycanes (GAGs), liés de manière covalente à une protéine porteuse. Les GAGs sont impliqués dans de nombreux processus biologiques, comme la croissance et la prolifération des cellules, et également dans de nombreuses pathologies, incluant l’arthrose, la maladie d’Alzheimer et des cancers. Leur biosynthèse fait intervenir des O-glycosyltransférases et commence par la formation de la zone de liaison tétrasaccharidique. Celle-ci initie la formation de deux types de chaînes de GAGs, les héparines / sulfates d’héparine avec l’action de l’EXTL3 et les sulfates de chondroïtines ou de dermatanes avec l’action de la CSGalNAcT-1. Dans cette biosynthèse, la zone de liaison peut être sulfatée mais le rôle de ces sulfatations est encore peu connu.L’objectif de ce travail était de synthétiser des disaccharides de la zone de liaison ainsi que les trisaccharides de transfert, avec le premier sucre aminé des chaînes de GAGs, diversement monosulfatés ou non, dans le but de comprendre le rôle de ces sulfatations sur les enzymes de bifurcation.Différentes méthodes d’activation, micro-ondes et chimie en flux continu, ont également été testées pour sulfater des mono-, di- et trisaccharides. / Proteoglycans are macromolecules composed of glycosaminoglycans chains (GAGs) covalently linked to a core protein. GAGs are implicated in many biological processes, such as cells growth and proliferation, and they are also involved in several diseases including osteoarthritis, Alzheimer’s disease and cancers. Their biosynthesis involves the action of O-glycosyltransferases and starts with the formation of a tetrasaccharidic linkage region. This GAGs linkage region initiates the formation of two types of GAGs chains, heparin/heparan sulfates with the action of EXTL3 and chondroitin sulfates/dermatan sulfates with the action of CSGalNAcT-1. In this biosynthesis, the linkage region may be sulfated, but the role of these sulfations is still poorly understood.The objective of this work was to synthetize disaccharides of the linkage region and transfer trisaccharides, with the first aminosugar of the GAGs chains, variously monosulfated or not, in order to study the role of sulfations on the bifurcation enzymes.Different activation methods, microwaves and flow chemistry, were also tested to sulfate mono-, di- and trisaccharides.

[pt] Materiais nanoestruturados como nanocristais semicondutores de telureto de cádmio (QDs de CdTe) e nanopartículas metálicas de prata (NPsAg) têm sido utilizados como nanosondas analíticas, explorando suas propriedades de luminescência e de ressonância de superfície plasmônica localizada (LSPR), respectivamente, sejam em dispersão coloidal ou em filmes finos. Em função das suas configurações experimentais, sistemas microfluídicos podem ser utilizados tanto para síntese de materiais nanoestruturados quanto para análise de analitos de interesses biológicos. No presente estudo, QDs-CdTe encapados com ácido tioglicólico (TGA) foram sintetizados em batelada e em regime de fluxo contínuo a partir da injeção dos precursores de cádmio e telúrio por bombas-seringas para um sistema de tubos de aço passando por fornos tubulares horizontais com controladores de temperatura (110-140 graus Celsius). Para otimizar os parâmetros experimentais foram variados a taxa de vazão volumétrica (0,15 - 0,03 mL min(-1)) e a razão molar de Cd:Te (1:0,3 - 1:1,5). Os resultados demonstraram que o efeito da razão molar na síntese de QDs apresentou ser mais significativo em comparação à variação da temperatura, obtendo QDs com FWHM de 64 – 86 nm. Filmes luminescentes poliméricos de PVA e PDMS foram desenvolvidos pelas técnicas de impregnação, mistura de QDs na matriz polimérica e por spin coating. Pela técnica de spin coating foram produzidos filmes de 58,7 nm. Filmes de QDs sobre substrato de vidro foram obtidos pelo processo de silanização da superfície do vidro. Todos os filmes apresentaram instabilidade de luminescência ao longo do tempo. Dispersões coloidais de NPsAg revestidas com ligantes orgânicos citrato e tartarato, nas razões Ag+:ligante (1:1 e 1:0,5), foram sintetizadas a partir da injeção dos ligantes e nitrato de prata por bombas-seringas em um microrreator tubular polimérico. As NPsAg-citrato e NPsAg-tartarato apresentaram cargas superficiais negativas e tamanhos médios de 12,5 nm. As bandas LSPR foram observadas para monitorar a interação entre as nanosonda de prata e os fármacos aminoglicosidico em fluxo contínuo mediante um fotômetro acoplado a uma cela de fluxo. Nas concentrações iguais ou maior que 2 × 10(-7) mol L(-1), produziu uma mudança no perfil espectral da nanosonda de NPsAg, com o decaimento do sinal no comprimento de onda 404 nm e o surgimento de uma nova banda em 480 nm, resultante da aglomeração das nanopartículas. Além disso, as NPsAg-tartarato foram depositadas sobre substrato de vidro para realização de filmes fino com objetivo de desenvolver, em parceria com a Universidade Federal de Pernambuco (UFPE), um biosensor baseado na ressonância plasmônica localizada (LSPR) para determinação do antígeno Candida albicans. / [en] Nanostructured materials such as cadmium telluride semiconductor nanocrystals (QDs-CdTe) and silver nanoparticles (NPsAg) have been used as analytical nanoprobes, exploiting their luminescence properties and localized plasmonic surface resonance (LSPR), respectively, both in colloidal suspension or on thin solid films. Due to their experimental set-up, microfluidic systems can be used, both, for synthesis of nanostructured materials and for the analytic detection of biological and pharmaceutical compounds. In the present study, thioglycolic acid (TGA) coated QDs-CdTe were synthesized in batch and in a continuous flow regime from the injection of cadmium and tellurium precursors by syringe pumps into a steel tubes through horizontal tubular furnaces with temperature controllers (110 - 140 Celsius degrees). To optimize the experimental conditions, we modulate the volumetric flow rate (0.15 - 0.03 mL min(-1)) and the Cd:Te molar ratio (1:0.3 - 1:1.5). The results showed that the effect of the molar ratio on the synthesis of QDs was more significant compared to the temperature variation, obtaining QDs with FWHM of 64 - 86 nm. Polimeric luminescent films with PDMS e PVA were developed with impregnation, mixing QDs-TGA in PDMS and PVA and spin coating techniques. By the spin coating technique we produced luminescent film of 58.7 nm thickness. QDs-TGA film on glass substrate were obtained by means of surface silanization.All the film showed luminescence instability over time. Colloidal dispersions of NPsAg coated with the organic citrate and tartrate ligands in the Ag+/ligand ratios (1:1 and 1:0.5) were synthesized from the injection of organic ligands and silver nitrate by syringe pumps into a polymeric tubular micro-reactor. NPsAg-citrate and NPsAg-tartrate presented negative surface charges and average sizes of 12.5. The SPR band was monitored to follow the interation between the silver nanoprobe with kanamycin and neomycin drugs by means of a flow cell coupled to a photometry. At concentrations equal or greater than 2 × 10(-7) mol L(-1) the LSPR band changed its spectral profile. LSPR maximum band, centered at 404 nm, decaied and appeared a new band at 480 nm resulting from the agglomeration of the nanoparticles. Moreover, in a partnership with the Federal University of Pernambuco (UFPE), NPsAg-tartarate were deposited on glass for the realization of thin film with the object to development a biosensor based on localized plasmon resonance (LSPR) for determination of Candida albicans antigen.

This thesis aims to investigate the use of additive manufacturing (AM) as a novel manufacturing process for the production of milli-scale chemical reaction systems. Five well developed additive manufacturing techniques; stereolithography (SL), selective laser melting (SLM), fused deposition modelling (FDM), ultrasonic additive manufacture (UAM) and selective laser sintering (SLS) were used to manufacture a number of miniaturised flow devices which were tested using a range of organic and inorganic reactions. SL was used to manufacture a range of functioning milli-scale flow devices from Accura 60 photoresin, with both simple and complex internal channel networks. These devices were used to perform a range of organic and inorganic reactions, including aldehyde and ketone functional group interconversions. Conversion of products within these reactors, were shown to be comparable to commercially available milli-scale coil reactors. More complex designs, which allowed SL parts to be integrated to existing flow and analytical instrumentation, allowed us to develop an automated reaction analysis and optimisation platform. This platform allowed precise control over the reaction conditions, including flow rate, temperature and reagent composition. We also designed a simplex type reaction optimisation software package that could input data in the form of reaction conversions, peak intensities, and thermocouple data, and generate a new set of optimal reaction conditions. SL parts which incorporated embedded analytical components were also manufactured, which allowed us to perform inline reaction analysis as a feedback method for input into the optimisation platform. Stereolithography was shown to be a highly versatile manufacturing method for designing and producing these flow devices, however the process was shown to be still limited by the range of processable materials currently commercially available. SLM was also used to manufacture a number of functioning milli-scale flow devices from stainless steel and titanium, which had simplistic internal channel designs of diameters ranging from 1 to 3 mm. Again, SLM parts were manufactured which incorporated embedded analytical components, which could be integrated into an automated reaction platform. These devices, unlike parts produced via SL, could be attached to heating platforms to allow us to perform high temperature reactions. This control over the reaction temperature formed an essential part of the reaction optimisation platform. These parts were again used to perform a ketone functional group interconversion. Internal structures of these SLM parts were also visualised via micro computed tomography (μCT or microCT) scanning as well as optical microscopy. FDM was used throughout the project as an inexpensive method of prototyping parts which were to be manufactured via more expensive manufacturing processes. This prototyping allowed the optimisation of intricate design features, such as the manufacture of an inline spectroscopic flow cell for integration with a commercially available LC system. FDM was also proposed as a customisable approach to designing and manufacturing flow devices with embedded components, however the current limitations in build resolution and materials choices severely limited the use of FDM for this application. UAM was also proposed as a novel manufacturing process whereby the build process would allow discrete components to be embedded directly into a flow channel. This was demonstrated by embedding a type-k thermocouple across a 2 mm channel. The data from this thermocouple was monitored during a heated reaction, and used as a method of determining the exact reaction conditions the reaction medium was being exposed to. SLS was also proposed as a possible manufacturing method for milli-scale flow devices, however it proved difficult to remove un-sintered powder from parts with internal channel diameters as high as 5 mm. It was shown that this powder was forming a dense semi solid, due to the large degree of shrinkage upon cooling of the SLS parts, which was compressing the powder. More research into optimum processing conditions is required before SLS could be used for the production of intricate channel networks.

No description available.

To make chemical analysis available both practically and economically, one approach is to miniaturise the equipment needed for the analysis. High-performance liquid chromatography (HPLC) is an example of a flow chemistry analysis system where active work is performed to achieve miniaturised systems. In this thesis, the focus is on creating a miniatyrised pump system constructed of pressurised CO2 (PCO) and a microfluidic chip with a restriction channel. The assignment of the PCO is to force a separate medium, which in this case is water, through the remaining system. The pump system will therefore be defined as pressure-driven, which has advantages as pulse-free flows. Utilising the latent energy from the PCO also reduces the need for electrical power, hence allowing a smaller battery. However, the pressure from the carbon dioxide source will gradually decrease as the content is consumed. To obtain continuous pressure, heaters have been integrated into the chip, and thus, the pressure drop can be controlled by changing the viscosity and density of the through-flowing fluid. A cooling table was also used to enable the cooling of the chip and thus further increase the pressure drop. PID control was implemented for the temperature to be adjusted to maintain a constant pressure downstream of the chip. By using this technology, runs of just over 80 minutes have been achieved with a pressure of 60 bar and a flow of 100 µl/min downstream, with a maximal error of around 0.03 bar. Then a chip adapted for water was used to control the water flow. Chips adapted for carbon dioxide placed right after the carbon dioxide source were also tested andruns of just over 10 minutes at 75 bar and 100 µl/min could be achieved with a maximal error closer to 1 bar. The pressure vessel used held a maximum of 100 ml of CO2 at 60 bar. The idea is that the pump system, in the end, will be applied for portable HPLC, and the PCO will then be stored in a cartridge, but in the experiments, a turned-off ISCO pump functioned as a carbon dioxide source.

L’attrait des compagnies pharmaceutiques pour des structures cycliques possédant des propriétés biologiques intéressantes par les compagnies pharmaceutiques a orienté les projets décrits dans ce mémoire. La synthèse rapide, efficace, verte et économique de ces structures suscite de plus en plus d’attention dans la littérature en raison des cibles biologiques visées qui deviennent de plus en plus complexes. Ce mémoire se divise en deux projets ciblant la synthèse de deux structures aromatiques importantes dans le monde de la chimie médicinale. Dans un premier temps, l’amélioration de la synthèse de dérivés phénoliques a été réalisée. L’apport de la chimie en flux continu dans le développement de voies synthétiques plus vertes et efficaces sera tout d’abord discuté. Ensuite, une revue des antécédents concernant l’hydroxylation d’halogénure d’aryle sera effectuée. Finalement, le développement d’une nouvelle approche rapide de synthèse des phénols utilisant la chimie en flux continu sera présenté, suivi d’un survol de ses avantages et ses limitations. Dans un deuxième temps, le développement d’une nouvelle méthodologie pour la formation de 3-aminoindazoles a été réalisé. Tout d’abord, un résumé de la littérature sur la synthèse de différents indazoles sera présenté. Ensuite, une présentation de deux méthodes efficaces d’activation de liens sera effectuée, soit l’activation d’amides par l’anhydride triflique et l’activation de liens C–H catalysée par des métaux de transition. Finalement, le développement d’une nouvelle méthodologie pour la synthèse de 3-aminoindazole utilisant ces deux approches sera discuté. / The continuous attraction towards accessing cyclic structures that possess interesting biological properties by pharmaceutical companies has guided the projects described in this M.Sc. thesis. Due to the increasing complexity of drug targets, methodologies encompassing efficient, rapid, economical and environmentally friendly syntheses are highly sought in the organic chemistry literature. The present work consists of two projects targeting the synthesis of two important aromatic structures in the field of medicinal chemistry. The first part of the thesis will present an improved synthesis of phenol derivatives. The recent chemical contributions in the continuous development of greener and efficient synthetic routes will be discussed, followed by a quick review of the literature on the hydroxylation of aryl halides. Then, the development of a new approach for rapid synthesis of phenol derivatives using continuous flow chemistry will be presented, including an overview of its benefits and limitations. The second part of the thesis will put forward the development of a novel methodology for the formation of 3-aminoindazoles. A summary of the literature on the synthesis of various indazoles will be presented, followed by an overview of two effective bond activation methods: the amide activation using triflic anhydride and transition metal catalyzed C–H activation. Finally, the evolution of a new method for the synthesis of 3-aminoindazole using the previously mentioned two approaches will be discussed.

No description available.

No description available.