Thèses sur le sujet « A-540 »

This master thesis has been written at the Department of Electric Power Engineering at the Norwegian University of Science and Technology. The work has been carried out at the Royal Institute of Technology in Stockholm, where the author spent the last year of his studies as an exchange student. In the thesis, six different designs of the electrical grid of a 540 MW offshore wind farm, placed 100km off the Norwegian coast, have been studied and compared. At this distance, AC cable transmission might be difficult because of the reactive power production in the cables. Taking this into consideration, two options for the transmission system to shore have been studied. In addition to the AC cable transmission, voltage source converter based HVDC transmission, in the form of HVDC Light, has been studied, giving a total of 12 models. The main scope of the thesis was to study the load flow situation and power system performance of the different offshore wind farm layouts. Two load flow cases were run for each model; the first studying the model when the active power transmission to shore was maximized, the second studying the model under a contingency situation. The reliability of the six designs was compared by calculating the expected number of cable failures during the life time of the wind farm for each design, and what consequence the disconnection of any cable would have on the power losses. In order to study the effect of the offshore grid design and transmission system design on the offshore power system stability, dynamic simulations have also been executed, and the voltage response and rotor speed response following a fault have been studied. All simulations have been executed in version 31 of the program PSS/E. The wind farm was modeled full scale, consisting of 108 wind turbines rated at 5MW. The wind turbines were modeled as doubly fed induction generators, using the generic wind model that comes with the program. The load flow simulations showed that an AC cable connection to shore gave lower total system losses than a DC connection for all designs. The lowest losses were found at the n-sided ring design in the AC/AC system, and the highest losses were found for the star design in the AC/DC system. These losses were 2.33% and 8.19% of the total installed capacity, respectively. In the dynamic simulations, a three phase short circuit fault, lasting 150ms, was applied at three different places in the system. The simulations showed that except from at the wind turbines that were islanded as a result of a fault, all dynamic responses were stable. The HVDC Light transmission to shore gave the highest voltage drops and the lowest voltage peaks offshore. Also, the maximum speed deviation was found to be larger when using HVDC Light transmission compared to using AC cables, with two exceptions; the radial and star designs when a fault was applied to the transmission system. A comparison of the six different grid designs showed that the results were varying. Based on the results in this thesis it has not been concluded that one of the offshore designs have better dynamic qualities than the other. The simulation results indicated that this is case specific, and more dependent on where in the offshore grid the fault occurs rather than the design of the offshore grid.

Durant les últimes dècades, els materials polimèrics han anat substituint els materials convencionals degut a que són més versàtils, menys densos i presenten interessants propietats. No obstant, presenten com a greu inconvenient, la seva inherent combustibilitat i en presència d'una font de calor i d'oxigen es cremen fàcil i ràpidament. El problema que es planteja és doble, ja que no només es perden les propietats del material sinó que el fum i els gasos tòxics que es desprenen són els principals responsables del perill que suposa un incendi.
En aquests darrers anys s'han desenvolupat diferents estratègies per minimitzar la inflamabilitat dels materials polimèrics, com són la incorporació d'additius o la modificació de l'estructura química dels polímers comercials i la síntesis de polímers específics. La primera opció, àmpliament utilitzada en la indústria per raons econòmiques, presenta alguns inconvenients, ja que els additius es poden extreure amb aigua o dissolvents, poden migrar i poden disminuir les propietats físiques i químiques del material. La incorporació de l'element químic responsable de la resistència al foc, de forma que estigui químicament enllaçat al polímer, permet solucionar part dels problemes abans mencionats per als additius.
Tot i que en aquests últims anys hi ha hagut un increment en el nombre d'heteroelements utilitzats com a retardants a la flama, el mercat està encara dominat per compostos halogenats. Aquests compostos que són altament efectius, interferint amb les reaccions responsables de la propagació de la flama, presenten com a greu inconvenient que durant la seva combustió es desprenen gasos molt tòxics i corrosius. Per aquest motiu, s'estan fent molts esforços en el camp de la investigació en la cerca de nous retardants a la flama lliures d'halògens, que siguin més respectuosos amb el medi ambient i menys agressius en cas d'un incendi. Els compostos fosforats i sililats han demostrat ser efectius retardants a la flama més respectuosos ambientalment.
Un altre problema dels materials polimèrics és l'encongiment que pateixen durant la polimerització i el curat, que té conseqüències negatives en el producte final. Per exemple, en polímers que s'utilitzen com adhesius, es poden trobar zones amb menor capacitat d'adhesió al substrat. Quan s'utilitzen com a recubriments es poden produir tensions internes que poden generar esquerdes i cavitats en el material, reduint la seva durabilitat. En l'actualitat, aquesta problemàtica s'està minimitzant incorporant càrregues, però aquesta metòdica presenta alguns inconvenients ja que augmenta la viscositat del sistema, dificultant el processat i condueix a materials més rígids i fràgils. Una alternativa és utilitzar el que es coneix com a "monòmers expandibles", és a dir, aquells que durant el procés de curat no sofreixen contracció o que fins i tot s'expandeixen lleugerament. Entre els monòmers expandibles més utilitzats es troben els espiroortoesters.
Amb aquests antecedents, el que es va proposar en aquest treball és l'obtenció de nous materials ignifugants, lliures d'halògens, que presentin un baix encongiment durant la polimerització i el curat. Per assolir aquest objectiu, s'han desenvolupat diferents estratègies que a continuació s'exposen breument:
1. Síntesi de nous monòmers basats en espiroortoesters que continguin fòsfor o silici en la seva estructura. En concret, s'han sintetitzat dos espiroortoesters fosforats, el propanoat de (1,4,6-trioxaespiro [4.4] nonà-2-il)-metil-3-[10-(9,10-dihidro-9-oxa-9-fosfafenantrè-10-òxid-10-il)] i el maleat de bis[(1,4,6-trioxaespiro [4.4] nonà-2-il)-metil 2-[10-(9,10-dihidro-9-oxa-9-fosfafenantrè-10-òxid)] i un de sililat, el propanoat de 1,4,6-trioxaespiro [4.4]-2-nonilmetil 3-trimetil silil. Aquests nous monòmers s'han obtingut amb bons rendiments mitjançant la modificació d'espiroortoesters prèviament sintetitzats en el laboratori a partir d'una reacció d'esterificació o una addició de Michael. Els espiroortoesters precursors s'han obtingut per al mètode tradicional, a partir de la reacció de la -butirolactona i un epòxid.
S'ha estudiat la polimerització i copolimerització d'aquests espiroortoesters amb reïnes epoxi comercials amb triflat d'iterbi com a iniciador.
A més, també s'ha estudiat l'efecte de combinar fòsfor i silici en el mateix material, amb l'objectiu d'investigar un possible sinergisme entre els dos elements.
2. Síntesi de nous polímers linials que continguin fósfor i grups espiroortoester en la cadena lateral, a través de copolimeritzacions radicalàries entre un espiroortoester que conté un grup acrilat en la seva estructura i diferents monòmers fosforats. Aquests nous polímers s'han entrecreuat posteriorment amb triflat d'iterbi com a iniciador catiònic, a través de la doble obertura de l'espiroortoester.
També, s'ha investigat la copolimerització catiònica entre el polímer lineal que conté un espiroortoester en la cadena lateral i diferents mescles de reïnes epoxi. Mitjançant l'ús de reïnes epoxi fosforades, prèviament sintetitzades al laboratori, s'ha introduït fòsfor en el material final, aconseguint així millorar les propietats de retardància a la flama.
3. Finalment, s'ha estudiat un nou mètode de copolimerització d'espiroortoesters amb reïnes epoxi utilitzant radiacions de microones, per tal de reduir el temps de curat, i s'han comparat els resultats amb el mètode d'escalfament convencional.
Over the last few decades, the polymeric materials has been replaced the conventional materials due to the versatility, low density, and their interesting properties. However, they present as an important limitation, their high flammability and in presence of heat and oxygen, they burn easily and rapidly. The problem is not only the destruction of the material but the smoke and toxic gases which are the main causes of hazards in a fire.
In the last years different strategies have been developed to minimize the flammability of polymeric materials, such as the use of additives, the modification of commercial polymers or through the synthesis of specific polymers. The first strategy is the most widely use in the industry because is the most economic way to achieve flame retardancy. Nevertheless, this method has several disadvantages, because the additives have to be used in relatively high concentrations and this may affect the physical and mechanical properties of the material. Also, additives may be leached, or may volatilize from the polymer during service. The alternative strategy is to use reactive flame retardants, where the flame retardant is covalently bonded to the polymer chains.
Although in the last few years there has been an increase of heteroelements used as flame retardants, the commercial market is still dominated by compounds based on halogens. These compounds present exceptional efficiency, interfering with the reactions responsible of flame propagation. However, during the combustion they release toxic and corrosive gases. Because of that, in the last few years has increased the interest in the research of halogen-free based flame retardants, such as phosphorus or silicon based flame retardants, which are more environmentally friendly and less aggressive in a fire.
Another problem of polymeric materials is the shrinkage during polymerization and polymer curing, and the consequences can be presented in many different forms. For example, in polymeric coatings poor adhesion of the substrate can be observed. In cast electrical insulators, polymerization shrinkage can produce internal stress in the polymer, which can reduce the durability of the material as a consequence of the appearance of microvoids and microcracks. The most common way to solve this problem is through the use of fillers, however this method present several problems, such as an increase of the viscosity which make difficult to fill molds. Another more advisable strategy is through the use of "expanding monomers", thus means, that during the polymerization and curing they don't shrink or even can produce some expansion. The spiroorthoesters are one kind of expanding monomers.
The main purpose of this thesis is the obtention of new environmentally flame retardant materials that present low shrinkage during polymerization and polymer curing. Several approaches have been developed to achieve these desired properties:
1. Synthesis of new monomers based on spiroorthoesters that contains phosphorus or silicon in their structure. It has been synthesized two spiroorthoesters with phosphorus, (1,4,6-trioxaspiro-[4.4] nonan-2-yl)-methyl 3-[10-(9,10-dihydro-9-oxa-9-phosphaphenanthrene-10-oxide-10-yl)] propanoate and bis[(1,4,6-trioxaspiro-[4.4] nonan-2-yl)-methyl 2-[10-(9,10-dihydro-9-oxa-9-phosphaphenanthrene-10-oxide-10-yl)] maleate and one with silicon in its structure, the 1,4,6-trioxaspiro [4.4]-2-nonylmethyl 3-trimethylsilyl propanoate. These new spiroorthoesters were synthesized with good yields through the modification of previously synthesized spiroorthoesters by a Michael addition or esterification reaction. The spiroorthoester moiety was obtained from -butirolactone and an epoxide.
These spiroorthoesters were polymerized and copolymerized with epoxy resins with ytterbium triflate as a cationic initiator.
Also, with the aim to investigate the possible synergistic effect between phosphorus and silicon were both combined into the same material.
2. Synthesis of linear polymers which contains phosphorus and spiroorthoester moieties in the side chain. They were obtained by radical polymerization from an acrylate-containing spiroorthoesters and different radically polymerizable phosphorus-containing comonomers. The polymers were crosslinked by a cationic double ring-opening of the spiroorthoester moieties with ytterbium triflate as an initiator.
Also, it was studied the cationic copolymerization of a linear polymer which contains a spiroorthoester moiety in the side chain with different epoxy resins. Through the use of phosphorus-containing glycidyl derivatives it was introduced phosphorus into the material.
3. It was studied a new method of copolymerization of spiroorthoesters with epoxy resins using microwave irradiation with the purpose to minimize the curing time. The results were compared with conventional heating conditions.

This thesis concerns with control calculation of steam boiler. The work is divided into several parts. In the individual parts are executed stechiometry calculations, the enthalpy of flue gas and power of the heat exchange surfaces. Based on the results it is proposed location of the SCR.

Ce travail s'inscrit dans le domaine très actif de la synthèse de polymères biosourcés. Les polymères époxy ont été choisis comme cible car ils présentent une double problématique de substitution du bisphénol A et d'utilisation de ressources renouvelables. L'objectif de ce travail est donc de préparer des polymères époxy biosourcés et d'évaluer leur potentiel en tant que substituts des solutions actuelles. Afin d'atteindre des propriétés thermo-mécaniques suffisantes, des composés naturels aromatiques doivent être utilisés. En effet, le cycle aromatique apporte rigidité et stabilité thermique au réseau. La vanilline est une des seules molécules aromatiques extraites de la biomasse qui soit disponible en quantités industrielles. Elle est obtenue par dépolymérisation en milieu basique et oxydant de lignine. Récemment, la préparation de polymères renouvelables à partir de vanilline a été intensivement explorée ; une revue sur ce sujet a été rédigée. La vanilline a servi de brique de base pour la préparation d'une plateforme de dérivés possédant des fonctionnalités variées. Des monomères diamine, diepoxy, ou dicyclocarbonate dérivés de vanilline ont – entre autres – été synthétisés. Les monomères diepoxy ont été réticulés avec un durcisseur amine commun et les polymères obtenus ont été caractérisés. Leurs propriétés thermo-mécaniques ont été reliées à la structure des monomères. Ces polymères époxy potentiellement biosourcés ont des propriétés comparables à la référence à base de bisphenol A. Afin de pouvoir moduler ces propriétés, des oligomères époxy de longueurs différentes ont été synthétisés à partir de vanilline selon la même méthode que celle utilisée industriellement. Ces oligomères et les polymères époxy qui en sont issus présentent effectivement des caractéristiques modulables. D'autres méthodes de contrôle des propriétés ont été testées, comme la préparation et la polymérisation de nouveaux durcisseurs aminés biosourcés, ou celle d'un monomère époxy trifonctionnel à partir de vanilline. Le polymère potentiellement biosourcé préparé à partir de ce dernier composé présente de meilleures propriétés que la référence à base de bisphénol A. Finalement, un travail portant plus sur la ressource a été réalisé. Des mélanges de composés phénoliques modélisant les produits obtenus lors du procédé de synthèse de vanilline à partir de lignine ont été préparés. L'utilisation de tels mélanges au lieu de la vanilline pure serait bénéfique autant économiquement qu'écologiquement. Ces mélanges ont été glycidylés, puis polymérisés, et les matériaux obtenus caractérisés. Les excellentes propriétés obtenues permettent d'envisager d'intégrer ce débouché à une bioraffinerie
The background of this work is the synthesis of bio-based polymers, a very active area of research. Epoxy thermosets were chosen as target because of the double problematic of bisphenol A substitution and of renewable resources use. Thus, the aim of this work is to prepare bio-based epoxy thermosets and to evaluate their potential as substitutes of current formulations. In order to display good thermo-mechanical properties, these polymers have to be prepared from renewable aromatics. Indeed, aromatic cycles bring rigidity and thermal stability to the network. Vanillin is one of the only aromatic molecules available from biomass at an industrial scale. It is obtained from the alkaline oxidative depolymerization of lignin. Recently, the preparation of renewable polymers from vanillin has been intensively explored; a review on this subject was compiled. Vanillin served as a building-block to prepare a platform of derivatives bearing various functions. Di-amine, di-epoxy, or di-(cyclic carbonate) monomers – among others – were synthesized. The di-epoxy monomers prepared were cross-linked with a common amine hardener and the polymers obtained were characterized. Their thermo-mechanical properties were linked to the monomers structure. These potentially bio-based epoxy thermosets have properties comparable to the bisphenol A-based reference. In order to tune these properties, vanillin-based epoxy oligomers were synthesized by the same method as the one used industrially. The properties of these oligomers and of the thermosets prepared from them could indeed be modulated. Other means of controlling the properties were tested, like the preparation and polymerization of new bio-based amine hardeners, or of a vanillin-based, tri-functional epoxy monomer. The thermoset prepared from this last compound displayed better properties than the bisphenol A-based reference. Finally, a work more centered on the resource was performed. Mixtures of phenolic compounds modelling the products of the lignin-to-vanillin process were prepared. The use of such mixtures instead of pure vanillin could be advantageous both from an economic and an ecologic point of view. These mixtures were glycidylated, polymerized, and the materials obtained were characterized. The excellent properties displayed by these materials allow a potential integration of this strategy in a bio-refinery

The colonization of immersed surfaces by a myriad of marine organisms is a complex, multi-stage, species-specific process giving rise to economic and environmental costs. This unwanted accumulation of organisms in the marine environment, called biofouling, has been attacked from different fronts, going from the ‘problem-elimination-as-problem-solving’ strategy (essentially through the use of biocides) to more elaborated and environmentally-friendly options based on the principle of ‘non-stick’ or ‘easy foul-release’ surfaces, which do not jeopardize marine life viability. Several marine organisms rely on proteinaceous adhesives to secure a holdfast to surfaces. Proteolytic enzymes have been demonstrated to be effective agents against settlement and settlement consolidation onto surfaces of marine bacteria, algae, and invertebrates, their proposed mode-of-action being the enzymatic degradation of the proteinaceous components of the adhesives. So far, however, the evidence remains inconclusive since most of the published investigations refer to commercial preparations where the enzyme is mixed with other components, like additives, which obviously act as additional experimental variables. This work aims at providing clear, conclusive evidence about the potential of serine proteases to target the adhesives produced by a group of model marine biofoulers. The strategy towards the goal consisted in the preparation and characterization of maleic anhydride copolymer nanocoatings modified by a surface-bound enzyme, Subtilisin A, the active constituent of the commercial preparations reported as effective against biofouling. The enzyme-containing maleic anhydride copolymer films were characterized (enzyme surface concentration, activity, stability, roughness and wettability) and thereafter tested in biological assays with three major biofoulers: spores of the green alga Ulva linza, cells of the pennate diatom Navicula perminuta, and cyprid larvae of the barnacle Balanus amphitrite. The purpose of the biological assays was to elucidate the efficacy of the immobilized catalyst to discourage settlement and/or to facilitate removal of these organisms from the bioactive layers. Results confirmed the initial hypotheses related to the enzymatic degradation of the biological adhesives: the immobilized protease was effective at reducing the adhesion strength of Ulva spores and Navicula diatoms in a manner that correlated with the enzyme activity and surface concentration, and deterred settlement of Balanus amphitrite barnacle cyprids even at the lowest surface activity tested. By facilitating the removal of biofilm-forming diatoms and of spores of the troublesome alga Ulva linza, as well as by interfering with the consolidation of adhesion of the calcareous Balanus amphitrite macrofouler, the enzyme-containing coatings here disclosed are considered to constitute an appealing and promising alternative to control marine biofouling without jeopardizing marine life.

Ce travail de thèse s'intéresse à la cycloaddition [2+2] asymétrique de cétènes et à son application en synthèse totale. La meilleure réactivité des oléfines Z comparées aux oléfines E, une des caractéristiques de la cycloaddition [2+2], est étudiée à la fois d'un point vue synthétique et théorique via des calculs DFT. Une méthodologie de cycloaddition [2+2] asymétrique entre des éthers d'énol chiraux et divers cétènes générés in situ a ensuite été développée. Cette cycloaddition limitée jusqu'ici à l'utilisation du dichlorocétène a été étendue à une grande variété de cétènes, permettant l'obtention de cyclobutanones variées hautement fonctionnalisées. Les cyclobutanones chirales obtenues ont été engagées dans la synthèse totale de produits naturels : la lactacystine et la salinosporamide A, inhibiteurs du protéasome et potentiels anticancéreux. Ces synthèses présentent trois étapes clés communes : une cycloaddition [2+2] asymétrique, une expansion de cycle de type Beckmann et la fonctionnalisation des chaînes latérales. La synthèse formelle de la lactacystine est présentée dans ce manuscrit, ainsi que les travaux en cours vers la synthèse de la salinosporamide A
This thesis work focuses on the [2+2] asymmetric cycloaddition of ketenes and its application in total synthesis. The best reactivity of Z olefins compared to E olefins, one of the features of the [2+2] cycloaddition, is studied both from a synthetic and theoretically point of view, via DFT calculations. A methodology of [2+2] asymmetric cycloaddition between chiral enol ethers and various in situ generated ketenes was then developed. Cycloadditions limited to the use of dichloroketene hitherto was extended to a wide range of ketenes, leading to various highly functionalized cyclobutanones. Those chiral cyclobutanones were engaged in the total synthesis of natural products: lactacystin and salinosporamide A, proteasome inhibitors and potent anticancer agent. These syntheses have three common key steps : a [2+2] asymmetric cycloaddition, a Beckmann type ring expansion and a side chains functionalization. The formal synthesis of lactacystin is presented in this manuscript, as well as the work in progress towards the synthesis of salinosporamide A

Las resinas epoxi son ampliamente utilizadas en soldaduras, recubrimientos, adhesivos y materiales compuestos. En algunas aplicaciones las resinas epoxi requieren de funciones especiales y versátiles, tales como alta adhesión a los sustratos, bajo encogimiento, bajo estrés térmico después del curado, buena dureza, baja inflamabilidad y buena resistencia química. La inflamabilidad de las resinas epoxi es una de las principales desventajas en su aplicación debido a que, como todo polímero orgánico, son inherentemente combustibles y en presencia de una fuente de calor y de oxígeno se queman fácil y rápidamente. Por consiguiente, algunos retardantes al fuego, tales como compuestos bromados, óxidos de antimonio, compuestos fósforo-halogenados, etc. son incorporados en las resinas epoxi para reducir su inflamabilidad. Estos compuestos son excepcionalmente efectivos pero presentan el inconveniente que incrementan las cantidades de humos y productos de descomposición tóxicos y corrosivos que se desprenden durante la combustión del polímero. Por esta serie de inconvenientes en la actualidad se ha incrementado la investigación de otros heteroátomos como retardantes a la llama para reemplazar a los halógenos.
En los últimos años se han descrito algunas aproximaciones sobre resinas epoxi con silicio unido covalentemente a la matriz polimérica. Así, han sido descritas modificaciones sobre resinas epoxi comerciales y copolimerizaciones de monómeros glicidílicos que contienen silicio con resinas epoxi comerciales, consiguiéndose una mejora de las propiedades retardantes a la llama sin sacrificar las propiedades mecánicas de la resina curada.
En este trabajo se ha planteado como objetivo general el desarrollo de resinas epoxi basadas en silicio con propiedades retardantes a la llama. Así, se ha llevado a cabo la síntesis de monómeros glicidílicos que contienen silicio en su estructura. Para establecer una relación entre la presencia y proporción del silicio y las propiedades físicas de los materiales resultantes, se han preparado polímeros termoestables a partir de mezclas de un glicidilo comercial con los monómeros que contienen silicio así como prepolímeros obtenidos a través de reacciones de crecimiento de cadena entre el DGEBA y un silanodiol. También se han sintetizado monómeros y agentes de curado que contienen fósforo en su estructura y se han preparado polímeros termoestables que contengan ambos heteroátomos. Con objeto de estudiar el mecanismo de reacción de monómeros que contienen silicio con aminas primarias, se ha sintetizado un monómero sililado monofuncional, fenilglicidiloxidimetilsilano (GDMPS), y se ha comparado su reactividad frente a una amina primaria, anilina, con la de un glicidilo comercial, fenilglicidiléter (PGE). El estudio cinético fue llevado a cabo mediante NIR y aplicando a los datos espectrales obtenidos métodos de análisis multivariante de resolución de curvas (MCR-ALS). Se ha llevado a cabo el estudio cinético del curado de un diglicidilo que contiene silicio, fenildiglicidiloximetilsilano (DGPMS), y de las mezclas de éste con DGEBA con una diamina primaria, DDM, mediante DSC isotérmico y dinámico. Además, se han estudiado los fenómenos de gelificacion y vitrificación de estos sistemas mediante DMTA en modo cizalla y TMDSC. Se han preparado polímeros termoestables y se han evaluado sus propiedades termodinamomecánicas, térmicas y de retardancia a la llama. Las propiedades termodinamomecánicas han sido estudiadas mediante DMTA en modo de flexión. La estabilidad térmica de estos compuestos se ha estudiado mediante análisis termogravimétrico en atmósfera de nitrógeno y de aire. Las propiedades de retardancia a la llama fueron evaluadas mediante el test ASTM-D-2683 del índice de oxígeno limitante (LOI). Finalmente, se ha estudiado la degradación térmica de los polímeros obtenidos para establecer el modo de actuación del silicio durante la degradación. Para ello, se ha realizado el estudio cinético de la degradación a partir datos obtenidos por TGA, estudios de las etapas iniciales de la degradación mediante quimioluminiscencia (QL) y la caracterización de los productos formados por TGA-MS, GC-MS, ATR-FTIR y DRX.
De los resultados obtenidos se han podido establecer las siguientes conclusiones: (1) Se ha determinado que la presencia del silicio produce un aumento en la reactividad del epóxido probablemente debido a efectos electrónicos. Esta mayor reactividad además reduce la importancia del camino autocatalítico en el curado con aminas primarias. (2) Las resinas epoxi sililadas termoestables muestran una disminución de la Tg y de la densidad de entrecruzamiento con el incremento del porcentaje de silicio.
Esta disminución está relacionada con un aumento del volumen libre debido a la mayor longitud de los enlaces Si-O. (3) Los polímeros termoestables que contienen silicio muestran un incremento del LOI a partir de un contenido de silicio del 3%. En los polímeros que contienen silicio y fósforo, se encontraron evidencias de la existencia de sinergia entre los dos heteroátomos. (4) La degradación de los polímeros que contienen silicio, tanto en atmósfera inerte como oxidante, conlleva la formación de oligómeros cíclicos de fenilmetilsiloxano, lo que implica que parte del silicio abandona la fase condensada. El residuo contiene silicio como SiO2, formando probablemente una capa aislante que actúa como barrera térmica y de transferencia de masa disminuyendo de esta manera la producción de volátiles.
The epoxy resins are widely used in coatings, adhesives, composites, etc. In some applications of epoxy resins special and versatile features are required, such as high adhesion to the substrates, low shrinkage, low thermal stress after curing, toughness, chemical resistance and low flammability. The flammability of epoxy resins is the main drawback in their application. Some flame retardants compounds, such as brominebased compounds, antimony oxides, phosphorous-halogen compounds etc. are incorporated in the epoxy resins to reduce their flammability. These compounds are exceptionally efficient but they have the inconvenience that they increase the smoke and toxic and corrosive gas evolution during the combustion of the polymer. For these drawbacks in the last years it has been increased the investigation of other heteroatoms like flame retardants to replace the halogens.
Some approaches about epoxy resins with silicon covalently bonded to the polymeric matrix have been reported. In this way, modifications of commercial epoxy resins and copolymerizations of silicon-based monomers with commercial epoxy resins giving to good flame retardancy, thermal and mechanical properties have been reported.
The aim of this thesis is the development of novel fire retardant silicon-based epoxy resins. Glycidyl monomers with silicon in their structure, prepolymers obtained by mean of growth of chain reactions between diphenyl silanediol and diglycidylether of bisphenol A (DGEBA) and a phosphorous-containing glycidyl monomer and two phosphorilated diamines were synthesized. Thermoset polymers were obtained from curing reactions of the compounds synthesized. To study the reaction kinetics of silicon-containing epoxy monomer with primary amines, a monofunctional silicon-containing epoxy monomer has been sinthesized, glycidyloxydimethylphenyl silane (GDMPS), and its reactivity with a primary amine, aniline, has been compared with that of a commercial epoxy monomer, phenylglycidylether (PGE). Kinetics studies were carried out by Near Infrared Spectroscopy (NIR) and applying to the spectral data obtained the multivariate resolution of curves methods. Likewise, the kinetic and curing behaviour studies for the difunctional silicon-containing epoxy monomer, diglycidyloxyphenylmethyl silane (DGPMS), and the mixtures of this monomer with DGEBA with a primary diamine, 4,4'- diaminediphenylmethane (DDM), have been carried out by means of isothermal and dynamic DSC. The gelation and vitrification for these systems have been studied by thermodinamechanical analysis (DMTA) with a shear sandwich clamp and modulated temperature differential scanning calorimetry (TMDSC).
The relationship between the amount of silicon and the thermodinamomechanical, thermal and flame retardancy properties of the thermoset materials obtained have been established. Thermoset materials were obtained from mixtures of commercial glycidyl monomer, DGEBA, with a silicon-containing glycidyl monomer, diglycidyloxyphenylmethyl silane (DGPMS), and their properties have been evaluated.
Thermodinamomechanical properties have been evaluated by DMTA using a 3-point bending clamp. The thermal stability have been analyzed by thermogravimetric analysis (TGA) in nitrogen and air atmospheres. The flame retardant properties have been evaluated by means of ASTM-D-2683, the limiting oxygen index test (LOI).
Finally, the thermal degradation of the silicon-containing polymers has been investigated by means of chemiluminiscence (CL), TGA-MS, GC-MS, ATR-FTIR and
DRX.
From the results obtained the following conclusions can be infered: (1) The silicon occurrence increases the reactivity of the epoxide due to electronic effects. This higher reactivity also reduces the importance of the autocatalytic path in the curing reactions with primary amines. (2) The thermoset epoxy resins showed a decrease in the Tg and the crosslinking density when the amount of silicon increases. This decrease is related with an increase of the free volume due to the Si-O and Si-C bonds. (3) The siliconcontaining thermosets show an increment of the LOI for silicon contents higher than 3%. In the polymers that contain silicon and phosphorous, there are evidences of the synergyc effect. (4) During the degradation of the silicon-containing materials in both, nitrogen and air atmospheres, cyclic siloxane oligomers were released. A silicon oxide rich char is formed, probably forming an insulating layer.

Polycyclic nitrogen containing heterocycles form the basic skeleton of numerous alkaloids and physiologically active drugs. Alloyohimbane was obtained from 3,4-dihydro-â-carboline using an iron-mediated [2+2+1] cycloaddition as the key-step. The bis-TMS-diyne was conveniently obtained by the C-alkylation of 3,4-dihydro-â-carboline followed by N-alkylation. Demetalation of the iron-complex followed by hydrogenation, E-ring expansion, and reduction provided alloyohimbane, a structurally and biologically interesting substance, via a linear eight-step sequence in 7% overall yield based on 3,4-dihydro-â-carboline. Another sequence provided (±)-alloyohimbane and (±)-3-epi-alloyohimbane in nine steps. The pyrrole unit occurs in a variety of naturally occurring compounds, pharmaceutical products and polymers. A novel two-step procedure for the synthesis of pyrroles by addition of a propargyl Grignard reagent to a Schiff base and subsequent silver(I)-promoted oxidative cyclization of the resulting homopropargylamine has been developed. The generality of this reaction was proven by the synthesis of a broad variety of substituted pyrroles using silver(I)-promoted cyclization. A three-step synthesis of (±)-harmicine, a natural product isolated from the Malaysian plant Kopsia griffithii having strong anti-leishmania activity, from 3,4-dihydro-â-carboline is achieved by addition of 3-trimethylsilylpropargyl Grignard reagent, Ag(I)-promoted oxidative cyclization to a pyrrole, and chemoselective hydrogenation of pyrrole ring. Total synthesis of anti-tumor active crispine A and biologically active 1,2,3,5,6,10b-hexahydropyrrolo[2,1-a]isoquinoline have been achieved in three steps using silver(I)-promoted oxidative cyclization as key step.

In dieser Dissertation wurden die ungewöhnlichen und einzigartigen Eigenschaften von Edelmetall-Clustern untersucht, die durch Quantum-Confinement im Sub-Nanometer-Bereich entstehen. Dabei zeigt sich, dass die chemischen und physikalischen Eigenschaften und damit die Funktionen nicht vom Festkörper abgeleitet werden können und stark von der Anzahl der Atome abhängen. Die erzielten theoretischen Ergebnisse wurden in enger Zusammenarbeit mit experimentell arbeitenden Partnergruppen erzielt. Dabei hat sich gezeigt, dass durch die enge Kooperation zwischen Theorie und Experiment ein tiefes Verständnis von fundamentalen Prozessen und den zugrunde liegenden Mechanismen erlangt werden kann. Im Rahmen dieser Dissertation wurden die Reaktivität von geladenen Goldoxid-Clustern in der Gasphase, die ultraschnelle Dynamik von Edelmetall-Clustern und deren Komplexen sowie die optischen Eigenschaften von kleinen, deponierten Silber-Clustern untersucht und damit Beiträge geliefert, die einzigartigen Eigenschaften von Edelmetall-Clustern im Zusammenhang mit der heterogenen Katalyse und Nano-Optik besser zu verstehen.
In this thesis, the unique novel properties of noble metal clusters which arise in the sub-nanometer size regime due to quantum confinement have been theoretically explored. It has been demonstrated that by adding or removing a single atom the chemical and physical properties and functionality of noble-metal clusters can strongly change. The theoretical results have been derived in close cooperation with experimental findings of partner groups demonstrating that by joint theoretical and experimental efforts thorough understanding of fundamental processes and underlying mechanisms can be achieved. This thesis addresses the reactivity of charged gas-phase gold-oxide clusters in the context of the heterogeneous gold nano-catalysis, the ultrafast dynamical properties of noble-metal clusters and their complexes, and the optical properties of silver clusters at surfaces.

Les aldéhydes sont des produits chimiques importants dans la synthèse organique, en raison de leurs vastes applications dans les cosmétiques, les produits pharmaceutiques et les herbicides. De plus, ils peuvent être convertis en composés à valeur ajoutée tels que des tensioactifs, des polymères, etc. Classiquement, les aldéhydes sont produits par hydroformylation ou ozonolyse réductrice des alcènes. Cependant, les deux méthodes souffrent de l'utilisation de catalyseurs coûteux et de ligands sophistiqués (hydroformylation) ou de la nécessité d'un procédé à forte intensité énergétique (ozonolyse). En conséquence, le développement d'approches plus durables pour la production d'aldéhydes est hautement souhaitable.Dans ce contexte, nous avons développé deux méthodes pour produire des aldéhydes à partir de dérivés d’acides gras insaturés. La première voie consiste à préparer des a-hydroxycétones grasses à partir de 1,2-diols et les couper pour obtenir des aldéhydes avec de bons rendements. Dans cette voie, deux systèmes catalytiques (homogènes et hétérogènes à base de métaux) ont été développés pour oxyder les diols vicinaux en a-hydroxycétones correspondantes. La coupure de ces espèces a été effectuée par un procédé de rétro-benzoin utilisant des sels de thiazolium thermiquement stables et les aldéhydes ont été récupérés par distillation réactive. La seconde voie repose sur la décomposition des ß-hydroxy hydroperoxydes gras facilement préparés à partir d'oléate de méthyle époxydé. De plus, la décomposition de l'espèce peroxyde a été étudiée dans des conditions thermiques pour donner des aldéhydes. Enfin, la coupure des 1,2-dicétones gras et la valorisation des aldéhydes ont également été étudiés pour conduire aux esters correspondants pouvant être utilisés comme monomères
Aldehydes are important chemicals in organic synthesis, due to their vast applications in cosmetics, pharmaceuticals and herbicides. Moreover, they can be converted to value-added compounds such as surfactants, polymers, etc. Conventionally, aldehydes are produced through hydroformylation or reductive ozonolysis of alkenes. However, both methods suffer from the use of expensive catalyst and sophisticated ligands (hydroformylation) or the requirement of high energy intensive process (ozonolysis). As a result, the development of more sustainable approaches for the production of aldehydes is highly desirable.In this context, we have developed two methods to produce aldehydes from unsaturated fatty acid derivatives. The first route involves the preparation of fatty a-hydroxyketones from 1,2-diols and their cleavage to give aldehydes with good yields. In this route, two catalytic systems (metal-based homogeneous and heterogeneous) have been developed to oxidize vicinal diols to corresponding a-hydroxyketones. The cleavage of these species has been carried out through a retro-benzoin process using thermally stable thiazolium salts and the aldehydes were recovered by reactive distillation. The second route relies on the decomposition of fatty ß-hydroxy hydroperoxides that are easily prepared from epoxidized methyl oleate. Moreover, the decomposition of the peroxide species was studied under thermal conditions to give aldehydes. Finally, the cleavage of fatty 1,2-diketones and the valorization of aldehydes were also studied to give the corresponding esters that could be used as monomers

Durante las últimas décadas, la sustitución de materiales convencionales por polímeros
sintéticos ha aumentado de forma importante debido a la multitud de aplicaciones, pero la
mayoría de ellos son extremadamente inflamables y en presencia de una fuente de calor y de xígeno se queman fácil y rápidamente.
La estrategia comúnmente más utilizada para minimizar la inflamabilidad de un
material, es la incorporación de sustancias retardamtes a la llama. Aunque en los últimos años ha habido un incremento en el número de heteroelementos utilizados en compuestos
retardantes a la llama, el mercado está todavía dominado por compuestos que contienen
halógenos, especialmente cloro y bromo. Estos compuestos, son muy efectivos ya sea como
aditivos o como reactivos pero presentan un inconveniente importante: incrementan las
cantidades de humos y productos de descomposición tóxicos que se desprenden durante la
combustión del polímero. Es por ello, que cada vez más se están dedicando grandes esfuerzos en investigación a la búsqueda de nuevos retardantes a la llama libres de halógenos, que
respeten el medio ambiente y no resulten agresivos.
El ácido bórico y sus sales han sido empleados como aditivos retardantes a la llama
desde 1800. La mayoría de retardantes a la llama que contienen boro se descomponen
térmicamente generando ácido bórico liberando agua en una reacción endotérmica, por tanto, pueden actuar como retardantes físicos al absorber calor en el proceso de descomposición,
diluir los volátiles en la fase gaseosa o formar una capa de vapor de agua sobre la fase sólida.
Además, el ácido bórico puede actuar formando un recubrimiento intumescente que
incrementa la efectividad de la capa protectora. Estos compuestos de boro son los más
utilizados, ya que resultan baratos y de amplia aplicación, pero presentan, al igual que todos
los aditivos, multiples desventajas frente a los reactivos retardantes a la llama. Los
compuestos organoborados que actúan como reactivos retardantes a la llama, no han sido
estudiados hasta, relativamente, hace poco tiempo, sin embargo, los resultados obtenidos
sobre la retardancia a la llama, en los diferentes polímeros modificados químicamente con
compuestos de boro, han sido satisfactorios.
Como objetivo general de este trabajo, se planteó la obtención de nuevos sistemas
poliméricos termoestables resistentes al fuego, libres de halógenos, sin detrimento de las
propiedades del material y que respeten el medio ambiente. Para ello se sintetizaron y
caracterizaron tres nuevos tipos de sistemas poliméricos basados en:
- Resinas novolaca con boro, obtenidas por modificación química de una resina
novolaca comercial con dos compuestos organoborados: bis(benzo-1,3,2-
dioxaborolanilo) y óxido de bis(4,4,5,5-tetrametil-1,3,2-dioxaborolanilo).
Posteriormente, con la finalidad de mejorar sus propiedades mecánicas, estas resinas
se entrecruzaron con hexametilentetraamina (HMTA) y diglicidil éter de bisfenol A
(DGEBA).
- Resinas epoxi-novolaca modificadas con compuestos organoborados y
posteriormente entrecruzadas térmicamente con catalizador.
- Polímeros estirénicos preparados a partir de monómeros que contienen boro.
Finalmente, se evaluaron las propiedades térmicas, termodinamomecánicas y de
retardancia a la llama de los sistemas anteriormente comentados. Pudiéndose concluir que el entrecruzamiento de las resinas novolaca con HMTA o DGEBA y de las epoxi-novolaca en presencia de un catalizador, permite obtener materiales con una buena integridad mecánica, permitiendo así establecer relaciones cualitativas de niveles de entrecruzamiento. La degradación térmica de las resinas modificadas con boro: resinas novolaca y resinas epoxinovolaca, y de los polímeros estirénicos borados, genera ácido bórico a elevadas temperaturas formando un residuo intumescente que retarda el proceso de degradación y evita que ésta sea total. Las resinas novolaca organoboradas, con contenidos de boro entre 2 y 4%, presentan excelentes propiedades de retardancia a la llama. En cambio, los polímeros estirénicos borados necesitan contenidos de al menos el 3% para manifestar buenas propiedades retardantes a la llama.
Although in the last decade there has been an increase in the number of heteroelements
used in flame retardants, the commercial market is still dominated by compounds containing halogens, notably chlorine and bromine. They are exceptionally efficient and may be incorporated as either additives or as reactives, but they do have such clear disadvantages as the generation of toxic and corrosive gases during thermal degradation. Recent developments in the chemistry of halogen-free flame retardant polymers involve polymers or reactive monomers that are inherently flame retarding such as those containing P, Si, B, N and other miscellaneous elements.
Boric acid and borate salts have been used as flame retardant additives since the early
1800s. Borates are effective flame retardants because impenetrable glass coatings form when they thermally degrade. The glass coatings form on the surface, and can contribute to the intumescent effect, because they exclude oxygen and prevent further propagation of
combustion. The water of hydration is lost by endothermic decomposition and therefore both dilutes and cools, by absorbing the thermal energy from the flame. However, additives have the disadvantage that they have to be used in relatively high concentrations (typically 30% by weight, or more) and this may affect the physical and mechanical properties of the polymers.
Also, additives may be leached, or may volatilise from the polymer during service. The
alternative strategy is to use reactive flame retardants, via copolymerization or some other
type of chemical modification (i.e. flame retardant groups that are inherently part of the
polymer backbone or that are covalently attached as side groups to the polymer).
The main aim of the present thesis is to develop new environment friendly flame
retardant thermosets, which are halogen free and have the good thermal and mechanical
properties of some standard materials. Synthetic approaches introduce boron into the
backbone of various polymers, so this main aim can be divided into four subsidiary aims:
− To synthesize and characterize boron-containing novolac resins obtained by
modifying novolac with organoboron compounds. These polymers were further
crosslinked with HMTA and DGEBA
− To synthesize and characterize epoxy-novolac resins, which are then further modified
with boron
− To synthesize and characterize boron-containing styrene monomers, which are then
further polymerized and copolymerized with styrene
− To evaluate the thermal, mechanical and flame retardancy properties of all the
polymeric systems synthesized
The conclusions drawn from the various studies of the present thesis can be summarized
as follows:
− The modification of the commercial novolac resin with organoboron compound
reaches a plateau at a modification degree of 65%
− The crosslinking of boron-modified novolac resin with HMTA is slower and less
extensive than that of commercial novolac resin because of the nitrogen coordination
from intermediate species with boron
− The crosslinking of commercial novolac resins with DGEBA needs a catalyst to be
added while the crosslinking of boron-containing novolac resins does not because the
boron itself acts as a catalyst
− The epoxy-novolac resins react with boron compounds mainly through the hydroxylic groups from halohydrin and opened glycidylic groups
− The thermal degradation of boron-containing novolac resins, boron-containing epoxynovolac resins and boron-containing styrenic polymers generates boric acid at high
temperatures to give an intumescent char that slows down the degradation and
prevents it from being total
− Novolac resins modified with boron content between 2 and 4%, show high LOI values
(above 38%)
− Boron-containing styrenic polymers show LOI values that increase with boron content
but boron contents need to be above 3% to achieve good flame retardant properties.

Die vorliegende Arbeit beinhaltet die Synthese neuartiger Hybridmaterialien basierend auf der Einlagerung optischer Materialien, wie Farbstoffmoleküle und Metallnanopartikel, in anorganische Wirtsmaterialien mit definierten Porenstrukturen. Hierfür wurden mikro- und mesoporöse alumosilikatische Verbindungen, wie z.B. Zeolithe und Vertreter aus der Familie der sogenannten „Mobile Composition of Matter“ (MCM), verwendet. Mit Hilfe dieses Konzeptes konnte z.B. der Einfluss der Wirtsmaterialien hinsichtlich ihrer Porengrößen und inneren Polarität auf die optischen Eigenschaften von photochromen Naphthopyranfarbstoffen untersucht werden. Neue photochrome Kompositmaterialien, welche sich durch einfache industrielle Prozesse, wie z.B. der Extrusion in eine Polymermatrix, weiterverarbeiten lassen, wurden auf diesem Wege synthetisiert. Durch die Einkapselung eines solvatochromen Spiropyranderivats innerhalb der Superkäfige von Faujasiten konnten Rückschlüsse auf die Polaritätsparameter der äußeren und inneren Oberfläche der Molekularsiebe gewonnen werden. Zudem wurde ein neues Synthesekonzept zur Herstellung fluoreszierender Silbernanopartikel innerhalb eines Zeolith Y entwickelt, um auf sehr einfachem Weg ein stabiles Material mit interessanten Fluoreszenzeigenschaften zu erhalten. Der Einfluss der Wirtsoberfläche auf fluoreszierende Farbstoffe wurde des Weiteren an Benzylidenketonfarbstoffen untersucht, die mittels „Ship in a Bottle reaction“ in Zeolith Y eingekapselt wurden. Um das Konzept zur Synthese optischer Effektpigmente zu erweitern, wurden neue photochrome Naphthopyrane, welche in Konjugation zu fluoreszierenden Farbstoffen stehen, synthetisiert und untersucht.

L'objectif du travail de recherche mené concerne l'élaboration des nouveaux matériaux d'électrodes modifiés pour des applications dans le domaine des biocapteurs. Le travail a été subdivisé en trois parties portant sur le greffage du sel de diazonium pour application immunocapteur, l'électroadressage des d'anticorps et l'électrodépôt d'un espaceur pour application aptacapteur. Dans la première partie de ce travail, nous nous sommes consacrés d'abord à l'électrogreffage du nitrobenzène diazonium sur la surface d'or pour le développement de capteurs immunologiques destinés à la détection de la bactérie Staphylococcus aureus. Une limite de détection de 10 UFC/mL a été atteinte. Dans la deuxième partie, la détection de l'ochratoxine A est présentée, basée sur l'électroadressage covalent de l'anticorps modifié par la fonction diazonium sur des électrodes de Diamant Dopé Bore (BDD). Une limite de détection de 0.007ng/mL a été obtenue et l'immunocapteur a été testé sur des échantillons réels. Enfin, on a développé un aptacapteur basé sur le greffage d'un espaceur (PEG) sur la surface des microcellules BDD pour la quantification de la biotoxine OTA. Une limite de détection de 0,01ng/L a été obtenue et application à un échantillon réel (le riz) a été démontrée. Les résultats obtenus, basés sur des méthodes électrochimiques de détection (variation de l'impédance ou du courant d'une sonde redox) sont encourageantes en termes de sensibilité, limite de détection, reproductibilité et spécificité
The objective of the research work was to the development of modified electrode materials for biosensor application. The work was devided into three parts: electrografting of diazonium salt for immunosensor application, electroadressing of antibodies and electrodeposition of PEG spacer for aptasensor application. In the first part of this work, the modification of gold surfaces with nitrobenzene diazonium cation was investigated in order to develop an immunosensors for the detection of Staphylococcus aureus. A detection limit of 10 CFU/mL has been obtained. The second part was focused on the electrically addressable deposition of diazonium functionalized antibodies on boron-doped diamond (BDD) microcells for the detection of OTA. A detection limit of 0.007ng/mL has been obtained and the immunosensor was tested on real samples. Finally, we developed an amperometric aptasensor based on electrochemical grafting of a PEG-COOH spacer on a BDD microcell for the detection of OTA biotoxin. A detection limit of 0.01 ng/L has been obtained and application to a real sample (rice) has been demonstrated. The amperometric and impedimetric techniques used in this work lead to promising results in terms of sensitivity, specificity and reproductibility

Cette thèse de doctorat a été réalisée au Centre de Recherche sur les Macromolécules Végétales (CERMAV) sous la direction du Dr Sébastien Fort, responsable de l'équipe Chimie et Biotechnologie des Oligosaccharides (CBO) et du Dr Sami Halila de l'équipe PhysicoChimie des Glycopolymères (PCG). Cette thèse intitulée « Synthèse par chimie click non metallo-catalysée de glycoconjugués macromoléculaires pour des applications médicales» est financée par le ministère de l'enseignement supérieur et de la recherche (bourse MESR). L'objectif de ce travail était de développer de nouvelles méthodes de modification et de couplage regiosélectif d'oligosaccharides pour la préparation de glycoconjugués par une chimie « click » sans catalyse métallique. Ces travaux s'appuient sur l'expertise de l'équipe CBO pour la synthèse chimio-enzymatique d'oligosaccharides complexes ainsi que sur les méthodes de modification sélective de la position réductrice des oses.Un premier aspect concerne l'utilisation des propriétés physico-chimiques des oligosaccharides pour l'obtention de nanoparticules de taille contrôlée. Ces particules sont constituées de copolymères à blocs hybrides obtenus par couplage entre un polymère de synthèse et un oligosaccharide. La structure des nano-objets préparés sera analysée au sein de l'équipe PCG.Le deuxième aspect concerne l'utilisation des propriétés de reconnaissance biochimique des oligosaccharides. Cette partie sera focalisée sur le couplage efficace d'oligosaccharides d'intérêt biologiques sur support solide pour la purification de protéines
The aim of the project is to develop new anomeric modification of oligosaccharides for the synthesis of glycoconjugates by metal-free click chemistry. Synthetic glycans have shown a great potential in medical and nanotechnology related fields. The current use of metallic catalyst during synthesis and the risk of contamination of the final product represent a drawback which could restrain their applications. Therefore an efficient metal free synthesis of glycoconjugates could be of great interest to circumvent this obstacle.Two distinct synthetic strategies have been explored for the metal free coupling of complex oligosaccharides on polymers to yield block-copolymers and glycoadsorbants. The glycopolymers were synthetized by a Michael addition between a thiol functionalized oligosaccharide and a maleimide or bromo-maleimide functionalized polymer. The nanoparticles obtained from the self-assembly of theses amphiphilic copolymers in water were characterized. The polycaprolactone-b-xylooligosaccharides copolymers presenting a reducible linkage were self-assembled into nanoparticles and assessed as model for the delivery of hydrophobic drugs. This system showed a selective release of the entrapped molecules in reducing environment making it an interesting system for the intra-tumoral delivery of anti-cancer drugs. Glycoadsorbents were prepared by a Diels Alder reaction between a solid matrix displaying a maleimide moiety and furyl functionalized oligosaccharides. The affinity matrixes obtained allowed the selective purification of lectins. The blood group antigen (A;B) grafted matrixes displayed good properties for the trapping of corresponding anti-A or anti-B antibodies. These types of immunoadsorbants have great potential for the treatment of immune diseases like the Guillain-Barré syndrome.To conclude, two efficient anomeric modification and coupling strategies of oligosaccharides have been developed, opening the way to the metal free synthesis of various glycoconjugates

Lab-on-a-chip (LOC) technology has blossomed into a major new technology fundamentally influencing the sciences of life and nature. From a systemic point of view however, microfluidics is still in its infancy. Here, we present the concept of a microfluidic central processing unit (CPU) which shows remarkable similarities to early electronic Von Neumann microprocessors. It combines both control and execution units and, moreover, the complete power supply on a single chip and introduces the decision-making ability regarding chemical information into fluidic integrated circuits (ICs). As a consequence of this system concept, the ICs process chemical information completely in a self-controlled manner and energetically self-sustaining. The ICs are fabricated by layer-by-layer deposition of several overlapping layers based on different intrinsically active polymers. As examples we present two microchips carrying out long-term monitoring of critical parameters by around-the-clock sampling.
Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

La chimie de clic est devenue indispensable dans les nombreux domaines de chimie associée à la conception de médicament. Dans ce contexte, comme nous savons(connaissons) l'étude concernant l'impact d'insertion triazole sur la conformation de peptaibol est limitée, nous avons conduit l'étude pour examiner l'impact et l'adaptabilité de 1, 1 4-disubstituted, 2, l'insertion 3-triazole dans peptaibols différent. Selon le résultat de cette expérience touchant à l'activité réduite et la conformation perturbée de l'analogue peptaibol, le substitut dipeptide décoré du fragment triazole portant substituents hydrophobe divers a été inséré à très N-ter la partie du peptaibol. L'amélioration du bioactivity et de la restauration de la conformation pour les analogues peptaibol a été observée et le fait a été aussi soutenu par les résultats obtenus de l'étude biophysique des analogues choisis d'ALM F50/5. Nous avons plus loin prolongé notre étude pour employer notre stratégie à être appliqué sur le peptide P42 thérapeutique qui souffre de la limitation de manque de perméabilité et de stabilité. Le peptide P42 est impliqué dans le pathophysiology de la maladie d'Huntington neurodégénératif. Un total de 12 analogues de peptide de P42-camelote a été synthétisé par SPPS par notre protocole optimize. Dans la deuxième partie, nous avons développé une stratégie pour synthétiser lipopeptide cyclique produit de l'espèce cynaobacterial marine. Notre objectif principal était de synthétiser Hormothamnin A, undecapeptide cyclique consistant de plusieurs acides aminés artificiels incluant dehydroamino acide (Dhaa) qui fait la synthèse de ce peptide compliqué. En raison de cette raison, premièrement, nous avons voulu appliquer notre stratégie de synthétiser Trichormamide A, une sorte relativement plus simple de cylic lipopeptide. Après l'accomplissement de cette tâche, une première tentative a été faite pour synthétiser Hormothamnin A. Le résultat préliminaire de ceci est présenté dans cette section. Enfin, nous avons essayé de développer une méthodologie robuste pour synthétiser Fmoc-Dhaa dans la phase de solution et son insertion dans l'ordre peptaibol par une norme(un standard) SPPS le protocole. Les résultats préliminaires que nous avons concernant la synthèse Dhaa et son insertion dans peptaibol sont aussi discutés ici de plus avec la synthèse de phase solide de Bergofungin naturel D
The click chemistry has become indispensible in the many areas of chemistry associated with drug design. In this context, as we know the study concerning the impact of triazole insertion on the conformation of peptaibol is limited, we have conducted the study to investigate the impact and adaptability of the 1, 4-disubstituted 1, 2, 3-triazole insertion into different peptaibols. Depending on the outcome of this experiment relating to reduced activity and perturbed conformation of the peptaibol analogue, the dipeptide surrogate decorated with the triazole moiety bearing various hydrophobic substituents was inserted at the very N-ter part of the peptaibol. The improvement of the bioactivity and restoration of the conformation for the peptaibol analogues was observed and the fact was also supported by the results obtained from the biophysical study of the selected analogues of ALM F50/5. We have further extended our study to employ our strategy to be applied on the therapeutic P42 peptide which suffers from the limitation of lack of permeability and stability. P42 peptide is involved in the pathophysiology of neurodegenerative Huntington’s disease. A total of 12 analogues of P42-TAT peptide were synthesized through SPPS by our optimized protocol. In the second part, we have developed a strategy for synthesizing the cyclic lipopeptide originated from marine cynaobacterial species. Our main objective was to synthesize Hormothamnin A, a cyclic undecapeptide consisting of several unnatural amino acids including dehydroamino acid (Dhaa) which makes the synthesis of this peptide complicated. Due to this reason, firstly, we have chosen to apply our strategy to synthesize Trichormamide A, a relatively simpler kind of cylic lipopeptide. After accomplishing this task, a first attempt was made to synthesize Hormothamnin A. The preliminary result of this is presented in this section. At last, we have tried to develop a robust methodology to synthesize Fmoc-Dhaa in solution phase and its insertion into the peptaibol sequence through a standard SPPS protocol. The preliminary results we have got concerning the Dhaa synthesis and its insertion into peptaibol are also discussed here in addition with the solid phase synthesis of natural Bergofungin D

En la present Tesi doctoral s’ha valorat el contingut fúngic d’un total de 18 mostres de compost: 7 procedents de la planta de compostatge de Manresa, 6 de la de Blanes, dues procedents de residu sòlid urbà processat a la planta de CESPA de Can Barba, (Vallès Occidental), dues de compost casolà de Pineda de Mar i, finalment, una procedent de femta de cavall obtinguda en un comerç especialitzat en productes de jardineria. Per a cada una de les mostres s’ha realitzat el càlcul de les unitats formadores de colònia de fong, ufc/g; s’han identificat els fongs de cada una de les mostres a nivell de gènere i se n’han seleccionat els Aspergillus i els Penicillium, que s’han incubat seguint el mètode de la FDA per a comprovar si poden produir les aflatoxines G2, G1, B2, B1 i l’OTA. Cap dels fongs potencialment micotoxigènics aïllats ha donat positiu en la producció de les toxines estudiades per sobre del límit de detecció quan s’han aplicat els mètodes cromatogràfics descrits en el treball. Per aquest motiu, s’estudia si el compost és un substrat adequat per a la producció d’aflatoxines incubant la soca de control Aspergillus parasiticus CECT 2681, descrita com a productora d’aflatoxines, sobre diferents proporcions de mescles d’arròs-compost. Després de comprovar que la soca control no pot produir les toxines quan el fong es desenvolupa sobre un 100% de compost, es comprova si pot continuar-ho fent sobre arròs. També es comprova si la soca control perd la seva capacitat micotoxigènica en ser incubada sobre compost i després sobre arròs. Per a realitzar aquesta anàlisi s’utilitza un mètode desenvolupat a la secció d’UHPLC-UV. Amb les diferents proves realitzades amb la soca de control Aspergillus parasiticus CECT 2681, es conclou que la soca control no perd la seva capacitat micotoxigènica en ser incubada primer sobre compost i després sobre arròs. També es pot concloure que el compost no és un bon substrat per a la producció d’aflatoxines ja que la producció d’aquestes disminueix en augmentar la proporció de compost en el substrat de creixement del fong.
En la presente Tesis doctoral se ha valorado el contenido fúngico de un total de 18 muestras de compost: 7 procedentes de la planta de compostaje de Manresa, 6 de la de Blanes, dos procedentes de residuo sólido urbano procesado en la planta de CESPA, Can Barba (Barcelona), dos de compost casero de Pineda de Mar y, finalmente, una procedente de heces de caballo obtenida en un comercio especializado en productos de jardinería. Para cada una de las muestras se ha realizado el cálculo de las unidades formadoras de colonia de hongo, ufc / g; se han identificado los hongos de cada una de las muestras a nivel de género y se han seleccionado los Aspergillus y Penicillium, que se han incubado siguiendo el método de la FDA, para comprobar si pueden producir las aflatoxinas G2, G1, B2, B1 y la OTA. Ninguno de los hongos potencialmente micotoxigénicos aislados ha dado positivo en la producción de las toxinas estudiadas por encima del límite de detección, cuando se han aplicado los métodos cromatográficos descritos en este trabajo. Por este motivo, se estudia si el compost es un sustrato adecuado para la producción de aflatoxinas incubando la cepa de control Aspergillus parasiticus CECT 2681, descrita como productora de aflatoxinas, sobre diferentes proporciones de mezclas de arroz - compost. Tras comprobar que la cepa control no puede producir las toxinas cuando el hongo se desarrolla sobre un 100% de compost, se comprueba si puede seguir haciéndolo sobre arroz. También se comprueba si la cepa control pierde su capacidad micotoxigénica al ser incubada sobre compost y luego sobre arroz. Para realizar este análisis se utiliza un método desarrollado en la sección de UHPLC-UV. Las diferentes pruebas realizadas con la cepa de control Aspergillus parasiticus CECT 2681, concluyen que la cepa control no pierde su capacidad micotoxigénica al ser incubada primero sobre compost y luego sobre arroz. También se puede concluir que el compost no es un buen sustrato para la producción de aflatoxinas ya que la producción de estas disminuye al aumentar la proporción de compost en el sustrato de crecimiento del hongo.
In this doctoral thesis we evaluated the fungal content of a total of 18 compost samples: 7 from the composting plant from Manresa, 6 from Blanes, 2 from urban solid waste from the processing plant CESPA, Can Barba (Vallès Occidental), two from homemade compost from Pineda de Mar and finally, one sample of fecal horse obtained in a trade specialized in gardening products. For each one of the samples the calculation of the fungus colony forming units, cfu / g, has been carried out; fungi have been identified for each of the samples at the level of genera. Aspergillus and Penicillium have been selected and have been incubated following the FDA method to verify if they can produce aflatoxins G2, G1, B2, B1 and OTA. Any of the isolated micotoxigenics fungi has positive production of the studied toxins over the detection limit when we have applied the chromatographic methods described in this work. For this reason, we study if compost is an appropriate substrate to produce aflatoxins by incubating control strain Aspergillus parasiticus CECT 2681, described as a producer of aflatoxins, in different proportions of rice-compost mixtures. After verifying that the control strain cannot produce toxins when the fungus grows on a 100% of compost, we verify if it can continue to produce toxins over the rice. It also verifies if the control strain loses its micotoxigenical capacity when it was incubated over compost and then over rice. To do this analysis we use a UHPLC-UV method developed in our section. To the different analyses realized with control strain Aspergillus parasiticus CECT 2681, we conclude that the strain does not lose its micotoxigenical capacity when being made on first and then incubated over rice. It can also be concluded that the compost is not a good substrate for aflatoxins production because the aflatoxins production decreases when the proportion of compost increases in the growth fungal substrate.

Les propriétés spectrales des composants fluorescents de la matière organique d’un sol naturel ont été étudiées dans les trois fractions physiques ; substances humiques, acide fulvique et acide humique, par la méthode des matrices d’excitation et d’émission de fluorescence couplée à l’algorithme Parallel Factor analysis (PARAFAC). Les modifications spectrales de ces composants ont été suivies (forme et pseudo-concentrations) en présence d’un contaminant de type hydrocarbure aromatique polycyclique (le benzo(a)pyrène (BaP), toxique et à caractère cancérigène) : (1) en faisant varier les volumes d’une solution pure de BaP dans chaque fraction de même concentration en matières organiques, (2) en faisant varier les concentrations en matière organique pour des concentrations fixes de BaP, qui ont été suivies dans le temps. Les résultats ont montré que le BaP influence d’une manière différente les fluorophores présents dans les trois fractions et ont permis de clarifier le type d’interactions avec une fraction ou l’autre. D’autre part, une discussion a été menée sur les paramètres de validation du nombre de composants pour le choix des modèles de PARAFAC
The spectral properties of the fluorescent components of the organic matter of a natural soil were studied in the three physical fractions; humic substances, fulvic acid and humic acid, by the method of the excitation and fluorescence emission matrices coupled to the Parallel Factor Analysis (PARAFAC) algorithm. The spectral modifications of these components were studied (form and pseudo-concentrations) in the presence of a polycyclic aromatic hydrocarbon contaminant (benzo (a) pyrene (BaP), toxic and carcinogenic): (1) by varying the volumes of a pure solution of BaP in each fraction having the same concentration of organic matter, (2) by varying the concentrations of organic matter for fixed concentrations of BaP, which were followed over time. The results showed that the BaP influences the fluorophores present in the three fractions in a different way and clarified the type of interactions with one fraction or the other. On the other hand, a discussion was held on parameters for validating the number of components for the selection of PARAFAC models

Stable, site-specific immobilization of redox proteins and enzymes is of great interest for the development of biosensors and biofuel cells, where the long-term stability of enzymatic electrodes as well as the possibility of controlling the orientation of the biomolecules at the electrode surface have a great importance. For such applications, it would be desirable to immobilise redox proteins and enzymes in a specific orientation on the electrode in order to improve direct electron transfer. In this work, we describe such an approach using site directed mutagenesis to introduce cysteine residues at specific locations on the enzyme surface, and the reaction between the free thiol of the cysteine and maleimide groups attached on the electrode surface to immobilise the mutated enzymes. Using cellobiose dehydrogenase (CDH) as a model system, different types of electrodes (carbon and gold-based, flat and nanostructured) were firstly modified with maleimide groups using a modular approach based on electrografting and solid-phase synthesis. Therefore, the electrodes were used to covalently immobilise CDH variants bearing the free cysteine in different locations at their surface. The key point of this method is that the main elements of the modification can be independently varied to tune the architecture of the electrode surface as required, by simply changing the “bricks” of the structure. The CDH-modified electrodes were tested for direct and mediated electron transfer, showing excellent long-term storage stability as well as good catalytic responses. The mechanisms of the direct and mediated electron transfer were fully investigated, as well as the kinetics of the CDH electrodic reactions, also employing computer simulations.

Leukotrienes are newly discovered metabolites of arachidonic acid believed to play a mediatory role in the pathogenesis of asthma. It was the intention, therefore to develop a leukotriene antagonist which may be clinically beneficial in this disease state. The known leukotrienes LT[C4], LTD[4], and LTE[4] were synthesised and studied in vitro on a range of animal tissues, which indicated the existence of three discrete leukotriene receptors. Synthesis of leukotriene analogues aimed at simplifying the agonist pharmacophore, resulted in the identification of a highly potent agonist of greater structural simplicity than the natural leukotrienes. From this starting point, using concepts of molecular rigidity and pharmacophoric group displacement, a compound was developed which antagonised the effects of the leukotrienes on the three receptor systems. This antagonist, bearing such a broad profile of activity, constitutes a major breakthrough in the field of leukotriene research.

Ce travail de thèse est consacré au développement d’un dispositif autarcique pour le contrôle des amphétamines dans les égouts. Il a été conçu dans le cadre du projet européen MicroMole pour aider la police scientifique à résoudre des scènes concernant la localisation des laboratoires clandestins d’amphétamines et produits dérivés. Il est composé de trois volets : le premier volet est dédié au développement de deux générations de capteurs potentiométriques sélectifs à l’amphétamine en utilisant le ionophore commercial dibenzo-18-crown-6 éther dans un premier temps puis le ion-pair complexe [amphetamine-H]+[3,3’-Co(1,2-C2B9H11)2]- synthétisé comme sites actifs pour la reconnaissance sélective d’amphétamine. Le deuxième volet est consacré au développement d’un système microfluidique passif permettant de contrôler le flux d’échantillon arrivant à la partie sensible du capteur en utilisant des micro-filtres et micro-mélangeurs. Le troisième et dernier volet est dédié à la conception et fabrication d’un système autonome d’échantillonnage miniaturisé pour le stockage des échantillons dans les égouts lors des enquêtes menées par la police scientifique correspondant à la localisation de laboratoires clandestins d’amphétamines
The work in this thesis is devoted to the development of an autarkic device for real-time monitoring of amphetamines in sewage. It has been developed within the EU project Micromole to help Law Enforcement Agents (LEA) to solve forensic scenarios related to the production of amphetamines and amphetamine-type stimulants (ATS). It is composed of three main sections. The first section is devoted to the development of two generation of potentiometric sensors for the detection of amphetamines using first, the commercial ionophore dibenzo-18-crown-6 ether, then the synthesized ion-pair complex [amphetamine-H]+[3,3’-Co(1,2-C2B9H11)2]- as active sites for amphetamine recognition. The second section is dedicated to the fabrication of a passive microfluidic system integrated into a Lab-on-a-Chip to protect the sensor from the harsh environment through the control of the sample amount reaching the sensor. For this purpose, the microfluidic system formed a combination of passive micromixers, microfilters and microchannels. The final section was devoted to the development of an autarkic sample storage unit to help LEA to store spontaneous samples during forensic investigations related to the clandestine production of amphetamines in illegal laboratories

Single molecule sensing using solid-state nanopores has sparked tremendous interest within the last decade, whether it be electrical or optical detection of biomolecules, their complexes or binding kinetics. Therefore, the main focus of this thesis was on developing a nanopore biosensor integrated into a microfluidic channel for in-flow electrochemical detection of DNA at single molecule level. By constituting such a compact planar device, nanopores can potentially be turned into future lab-on-chip biosensors with a capability of in-flow single molecule detection. Two different types of nanopore materials were initially fabricated; a novel ultra thin PI membrane and SiN, and characterized in terms of nanopore conductance and electric noise. An alternative approach to locally and gradually thin SiN nanopores using Reactive Ion Etch technique was also presented with detailed fabrication, optimization and characterization steps. DNA translocation using polymer and thinned SiN nanopores was shown at the end of each fabrication chapter. On account of their compatibility with microfluidic integration, SiN nanopore chip was compacted into a PDMS microfluidic channel for the purpose of creating potential single molecule detection capabilities under continuous flow conditions. The introduction of flow to the nanopore system is important, because it would ideally bring the benefit of simultaneous electrochemical detection of biological entities in flow, where the idea of lab-on-chip biosensing devices is built upon. To characterize the rheological properties of DNA and flow characteristics, optical experiments were carried out using Confocal Microscopy and Fluorescence Correlation Spectroscopy. The effect of flow rate on the basics of nanopore detection (e.g. nanopore conductance and noise) was discussed, and investigated experimentally. Last, DNA translocation in the absence and the presence of flow was studied as a proof-of-principle. The investigation of detection capability of the integrated device using the chosen flow rates sets the basics for the future applications of nanopore-integrated microfluidic systems (e.g. on-nanopore chip capillary electrophoresis).

Depuis la mise sur le marché de l'imatinib (ou Gleevec®), les protéines kinases sont devenues des cibles thérapeutiques privilégiées dans le traitement de multiples pathologies. Parmi les huit groupes de protéines kinases, le groupe CMGC contient 61 kinases sérine-thréonine, dont les CDKs (cyclin-dependent kinases), les GSK3 (glycogen synthase kinase 3), les CLKs (Cdc2-like kinases) ou encore les DYRKs (dual specificity,tyrosine phosphorylation-regulated kinases). Néanmoins, l'un des défis majeurs dans le développement d'inhibiteurs de kinases reste la sélectivité vis-à-vis des autres protéines kinases car la majorité de ces composés se place dans la poche ATP, site commun à toutes ces protéines. L'objectif de notre équipe est de synthétiser de nouveaux inhibiteurs sélectifs des protéines kinases du groupe CMGC. Dans cette présentation, nous décrirons la synthèse, l'évaluation des relations structure-activité et l'optimisation de la sélectivité de trois séries d'inhibiteurs hétérocycliques. A partir de l'inhibiteur N-&-N1 (GP0210) développé dans notre laboratoire et actuellement en phase préclinique, la synthèse et l'évaluation biologique d'une nouvelle chimiothèque de pyrazolo[1,5-a]triazines ont permis d'identifier deux séries de composés responsables de l'inhibition d'une part de CDKs et d'autre part de GSK3. Sur la base du composé AT7519, inhibiteur de CDKs et GSK3 actuellement en phase clinique en oncologie, nous avons découvert de nouveaux pyrazole-3-carboxamides, inhibiteurs sélectifs de GSK3 avec de nouvelles indications thérapeutiques. Enfin, nous avons préparé des dérivés de la famille des mériolines, inhibiteurs non sélectifs de protéines kinases, présentant des activités d'inhibition nanomolaires sur les kinases CLKs et une sélectivité vis-à-vis des autres protéines kinases du groupe CMGC, en particulier les DYRKs. Ce dernier résultat n'avait jamais été observé jusqu'à ce jour
Since the approval of imatinib (or Gleevec®), protein kinases have become major targets for the treatment of several pathologies (cancer, neurodegenerative diseases,…). Among the eight existing groups of protein kinases, the CMGC group consists of 61 serine-threonine kinases classified as CDKs (cyclin-dependent kinases), GSK3 (glycogen synthase kinases), CLKs (Cdc2-like kinases), DYRKs (dual specificity, tyrosine phosphorylationregulated kinases) or other sub-families. Nevertheless a major challenge remains concerning the development of kinase-modulating small molecules: the selectivity of these new inhibitors, which generally bind in the ATPbinding pocket, a common site for all protein kinases. Our team aims at synthesizing original and selective inhibitors of CMGC kinases. In this presentation, we are introducing the synthesis, the evaluation of the structure-activity relationships and the optimization of the selectivity of three series of heterocyclic inhibitors, targeting CMGC protein kinases. Based on N-&-N1 (GP0210), an inhibitor developed in the laboratory and currently in preclinical trials, the synthesis and the biological evaluation of a library of pyrazolo[1,5-a]triazines led to the identification of two series of compounds which inhibit CDK on the one hand and GSK3 on the other hand. From AT7519, a CDK and GSK3 inhibitor currently in phase II clinical trials in oncology, we synthesized new pyrazole-3-carboxamides, which are selective GSK3 inhibitors and may have different therapeutical applications. Finally we prepared derivatives of meriolines, CDK inhibitors that have been previously developed in our laboratory. These new compounds inhibit CLKs on the nanomolar scale and are selective against other CMGC kinases, especially against DYRKs. This last result has never been obtained so far

A high voltage DC electric field was applied to methane and hydrogen flames using electrodes in a point to plane configuration. In a methane flame the Townsend mechanisms were observed along with the streamer, glow and spark corona discharge and were characterised using electrical, visual, audio and mass spectrometry data. A Pt point electrode was used to explore the region where the Townsend mechanisms took place by taking full mass spectrums from 10 – 50 amu for various voltages, varying oxygen concentration and using different inert gases. Large decreases in H2O and CO2 was observed in the ratio of 2:1 while an increase of N2 and O2 was also seen. These changes were attributed to transport effects moving the H2O and CO2 molecules away from the sample inlet. As the H2O and CO2 molecules were displaced, air was drawn in which caused the appearance of an increase in N2 and O2. One possible explanation for the transport effect is the electric field ionized O2 while the positive electrode repelled the ions. It is this movement that then pushes the H2O and CO2 molecules away from the sample inlet. The effect of a spark corona discharge on SO2 and CO2 in a hydrogen flame was also explored. Both were observed to decrease upon the creation of the discharge. Again transport effects could be used to explain these findings. The thesis also documents the design and creation of an automated experimental system used to obtain the results. This included hardware design, controlling software and scripts to analyse the large volume of data. The platform enabled an experimenter to control the gas flow, electrode placement, voltage and current applied automatically, while taking synchronised voltage, current, audio, visual and mass spectrometry data.

Understanding the origin of life is one of the foremost challenges for science. Despite the immense diversity displayed by biology on the macroscopic scale, cellular biochemistry is at its most fundamental level remarkably uniform. Recognising the minimal elements of biochemistry required for a living system represents one task within origins of life research, whereas the other is understanding the organic chemistry which could have led to their spontaneous organisation on the abiotic Earth. Significant attention has been paid to the prebiotic generation and assembly of the components of nucleic acids resulting in the demonstration of important prebiotic syntheses and in the uncovering of various key problems which have seeded much informative discussion within the prebiotic community. However, experimental investigations into the assembly of key sets of ubiquitous metabolites have been comparatively lacking and will be necessary to assess the relevance of central metabolic pathways to the earliest stages in the development of life. Presented herein are investigations into the prebiotic chemistry of a selection of small molecules central to one of the most fundamental and highly conserved metabolic pathways found in biology; triose glycolysis. By utilising a prebiotically relevant method of specifically generating aldehyde-2-phosphates from simple sugar precursors, it has been shown that several intermediates common to glycolysis can be generated in high yield under mild, aqueous conditions in a simple step-wise sequence which culminates in the generation (for the first time under prebiotically relevant conditions) of the highest-energy organophosphate utilised by nature; phosphoenolpyruvate. Based on the demonstrated transformations, a potentially prebiotic network of glycolytic reactions is proposed, sharing common precursors and reaction conditions with important existing work within the field concerning the generation of nucleotides, amino-acids and lipids. The predisposition of hydroxy-aldehydes to glycolytically important transformations and the relationship of the proposed prebiotic network to extant glycolysis is discussed.

Cruentaren A, a highly cytotoxic metabolite, which also inhibits F-ATPase, was synthesized using our recently developed methodology on resorcylic acid lactones natural products. [Molecular structure diagrams appear here. To view, please open pdf attachment] Alcohol A was prepared on a multigram scale in 13 steps starting from (S)-Roche ester and using highly stereoselective reactions such as Evans aldol reaction and asymmetric propargylation. [Molecular structure diagrams appear here. To view, please open pdf attachment] Key fragment B was synthesized in 11 steps from 1,3-propanediol. The 1,2-anti-configuration was installed with a Brown crotylation. Diketo-dioxinone D was generated from C-acylation between Weinreb amide B and keto-dioxinone C. Ketene generation by thermolysis followed by trapping with alcohol A and aromatization afforded resorcylate derivative E. [Molecular structure diagrams appear here. To view, please open pdf attachment] Finally after a sequence consisting of the following key steps: ring closing alkyne metathesis, coupling between amine G and acid H and Lindlar hydrogenation, cruentaren A was obtained.

Cette thèse explore deux voies d’amélioration des performances d'un biocapteur électrochimique d'affinité pour la détection des anticorps anti-NS1 de la dengue.La première volonté est l'amélioration de la limite de détection et de la sensibilité des biocapteurs par microstructuration du transducteur. Une modélisation basée sur les éléments finis a permis de définir la gamme optimale des paramètres géométriques des microplots. Après construction, les électrodes recouvertes de microplots ont été caractérisées par voltampérométrie cyclique et par microscopie électronique à balayage. A l'issue de l'optimisation, des biocapteurs à glucose ont été construits afin de démontrer l'accroissement des performances d’un biocapteur ampérométrique. Enfin, dans le but de valider l'intérêt des microplots pour un biocapteur d'affinité, un modèle d'immunocapteur impédance métrique sans marquage permettant la quantification de l'anticorps de la sous-unité B de la toxine du choléra est étudié avant de procéder à la réalisation d'un immunocapteur d'intérêt pour l'anticorps de la dengue. Ils sont réalisés sur deux types d'électrodes : les électrodes recouvertes de microplots et des électrodes interdigitées.La seconde volonté est l'amélioration de la longévité du stockage des biocapteurs à flux latéral par microencapsulation des biomolécules marquées, nécessaires à la détection par compétition. Pour cela, des microcapsules de polymère, fabriquées à faible coût, sont développées. Le bleu de méthylène et l'enzyme glucose oxydase ont été encapsulées sous forme sèche. Leur relargage a été suivi par spectrophotométrie UV-Visible et/ou par électrochimie après cassure des microcapsules par action mécanique et/ou par ultrasons
This thesis explores two ways to enhance the performance of an electrochemical affinity biosensor for the detection of dengue anti-NS1 antibodies.The first goal was to improve the limit of detection and sensitivity of biosensors using microstructuration of the transducer. Based on finite element modelling, an optimal range of the microcone geometric parameters was defined. After construction, the microcone-covered electrodes were characterised using cyclic voltammetry and scanning electron microscopy. At the end of the optimisation process, glucose biosensors were fabricated to demonstrate the increased performance gains of an amperometric biosensing platform. Finally, in order to validate the interest of the microcones for an affinity biosensor, a label-free impedimetric immunosensor allowing the quantification of the cholera toxin B-subunit was studied as a model before performing an immunosensor of interest for dengue antibodies. The immunosensors were made on two types of electrodes: microcone-coated electrodes and interdigitated electrodes.A second goal was to improve the shelf-life of lateral-flow biosensors by microencapsulating labelled biomolecules, mandatory for competitive detection. For this purpose, low-cost polymer microcapsules have been developed. Methylene blue and an enzyme, glucose oxidase, were encapsulated in a dry state. Their release was followed by UV-visible spectroscopy and/or electrochemistry after breaking the microcapsules by mechanical action and/or with ultrasonic agitation

La polimerització radicalària controlada catalitzada per Cu(0) es una de les metodologies més importants en l’àmbit de les polimeritzacions radicalàries degut a seva simplicitat i la possibilitat de sintetitzar polímers amb estructures ben definides i arquitectures complexes. En aquesta mateixa línia el desenvolupament de sistemes polimèrics capaços d’encapsular i alliberar fàrmacs es una de les línies de investigació més explotades e investigades en els darrers anys, ja que millorar la solubilitat de fàrmacs hidrofòbics i alliberar-los sota la presencia de certs estímuls biològics segueix sent una tasca bastant laboriosa. El objectiu principal d’aquesta tesis es investigar la polimerització radicalària catalitzada per Cu(0) en presencia de sistemes bifàsics i tanmateix explorar el potencial i les limitacions d’aquesta metodologia per obtindré polímers amb una estructura perfectament definida. En ultima instancia l’aplicació d’aquest tipus de polimerització radicalària catalitzada i altres mètodes de polimerització seran emprats per la síntesi de polímers sensibles a certs estímuls i amb la finalitat d’encapsular fàrmacs per actuar com vehicles en l’alliberació controlada dels mateixos.
La polimerización radicalaria catalizada por Cu(0) es una de las principales metodologías en el campo de las polimerizaciones radicalarias debido a su alto grado de simplicidad i la posibilidad de sintetizar polímeros con estructuras perfectamente definidas. En esta misma línea el desarrollo de sistemas poliméricos capaces de encapsular fármacos es una línea de investigación en constante desarrollo y de gran interés ya que la necesidad de mejorar la solubilidad de fármacos hidrofóbicos y liberarlos bajo la presencia de determinados estímulos de biológica relevancia sigue siendo una tarea complicada. El objetivo principal de esta tesis es investigar la polimerización radicalaria catalizada por Cu(0) en sistemas bifásicos con el objetivo de obtener polímeros con un alto grado de estructura definida. En última instancia la aplicación de este tipo de polimerización radicalaria junto con otros métodos de polimerización será empleado para el desarrollo de polímeros sensibles a ciertos estímulos de biológica relevancia con la finalidad encapsular fármacos y liberarlos de manera controlada.
Cu(0)wire-catalyzed SET-LRP has been postulated as one of the most versatile LRP techniques due to its operational simplicity which enables the construction of well-defined polymers and more complex architectures. In particular, the development of polymeric materials with suitable applications for medicine (e.g. polymeric nanoparticles able to encapsulate and release drugs) is a field of growing interest since they improve the poor solubility of hydrophobic drugs in aqueous media. However, their selective delivery under the application of different biological relevant stimuli still remains challenging. The main objective of this thesis is to investigate the Cu(0)wire-catalyzed SET-LRP in “programmed” biphasic systems and to explore the potential and limitations of this methodology with the ultimate goal of obtaining well-defined polymers with complex architectures and maximum end-group fidelity. Eventually, the application of biphasic SET-LRP and other polymerization techniques has been used for the synthesis of stimuli cleavage polymers and their potential application as drug delivery systems has been studied.