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Les MOFs résultent de l’organisation de polyèdres métalliques reliés par des molécules organiques chélatantes pour former un réseau poreux. La construction de solides hybrides organiques/inorganiques permet d’imaginer un très grand nombre de matériaux aux propriétés structurales et physico-chimiques variées. Le confinement du substrat dans une structure rigide, associé à des propriétés particulières des clusters métalliques ainsi qu’à des parois pouvant être fonctionnalisées, fournissent un environnement catalytique unique, plaçant les MOF à la frontière entre les espèces types zéolites et les enzymes. Cependant, il existe aujourd’hui très peu de MOFs possédant plus d’une fonction catalytique. Néanmoins, les propriétés catalytiques des MOFs peuvent être améliorées de façons non négligeables grâce aux méthodes de post-fonctionalisation. Dans ce travail, nous reportons le développement d’une méthode de post-fonctionnalisation originale des amino-MOFs. La première étape consiste à convertir la fonction amine en fonction azoture. Puis, sans isolation ni purification, le MOF fonctionnalisé est obtenu par « Click Chemistry » en ajoutant l’alcyne correspondant. Cette méthode peut être appliquée à tous les types d’amino-MOFs et à quasi toutes les fonctions chimiques que l’on souhaite greffer. Une large librairie de nouveaux matériaux a ainsi été obtenue et complètement caractérisée. Cette méthode a aussi été utilisée pour créer des MOFs catalytiques à façon pour une réaction de transesterification, ainsi que pour l’investigation de nouvelles applications plus fines (niches industrielle) / MOFs result from the association of metallic clusters connected by organic linkers to form a net. It is acknowledged that ultimately MOFs could mimic “enzymes” using “molecular recognition” concept to allow high chemio-, regio-, enantio-selectivity. We could indeed anticipate MOFs as potential “artificial enzymes” that can combine several properties at the nanometer scale in a concerted fashion. However to date, the number of MOFs with more than one reactive “catalytic” function is rather scarce. A key to address advanced MOF materials suitable for more sophisticated applications is to add functionalities of greater complexity in a controlled manner. The ability to modify the chemical environment of the cavities within MOFs would allow tuning of the interactions with guest species, and serve as a route to tailor the chemical reactivity of the framework. However, the introduction of reactive chemical functions by self-assembly methods is not a trivial task. In this work, we report an original PSM method starting from amino derived MOFs. The first step consists in converting the amino group into azide (N3). Without isolation nor purification, the desired functionalized material is obtained by grafting the corresponding alkyne using “Clik Chemistry”. This method can be applied to all kind of amino-MOFs and to all kind of grafted chemical functions. A diverse library of original MOFs was synthesized and characterized. Finally, this method was used to engineer catalytic MOFs for the transesterification of ethyldecanoate with methanol or to investigate applications in specialized industrial niches

A tripanossomíase sul-americana, também conhecida como Doença de Chagas é uma enfermidade endêmica da América Latina.A doença é causada pelo protozoário Trypanosoma cruzi, cuja transmissão em seres humanos e outros mamíferos ocorrem, principalmente, através das fezes do inseto \"barbeiro\" (triatoma infestans) infectado.Desde a descoberta já foram realizadas inúmeras tentativas de tratamento sem obter quimioterapia eficaz. Hoje o tratamento é realizado pelo uso do fármaco nitroheterocíclico benznidazol. Porém esse composto só é utilizado na fase aguda da doença e tem sua eficácia variada de acordo com a área geográfica, provavelmente como consequência de variação de cepas do parasita e apresenta graves efeitos colaterais. Uma ferramenta interessante em Química Medicinal é o uso do bioisosterismo para a síntese de moléculas análogas, que por possuírem propriedades biológicas relacionáveis geralmente atuam no mesmo alvo farmacológico como agonistas ou antagonistas. Por outro lado, as reações relacionadas às condensações de cicloadição 1,3 dipolar catalisadas por Cu(I), envolvendo estratégias de \"click chemistry\" tem como pontos positivos o fato de geralmente não formarem subprodutos, serem de fácil execução e apresentarem rendimentos elevados. Partindo de dois compostos comerciais (benzilamina e cloreto de cloro acetila) efetuou-se a síntese de uma biblioteca de vinte e três compostos análogos ao benznidazol através de uma rota sintética curta e de fácil execução. Foram realizados ensaios de atividade tripanocida envolvendo a cepa Tulahuen de T.cruzi, bem como ensaios de citotoxicidade. / The South American trypanosomiasis, also known as Chagas\' disease is an endemic disease in Latin America. The disease is caused by the protozoan Trypanosoma cruzi, whose transmission in humans and other mammals occur primarily through the faeces of the insect \"barbeiro\" (triatoma infestans) infection. Since the discovery already been carried out many attempts to obtain effective chemotherapy treatment. Today\'s treatment is accomplished through the use of the drug nitro-heterocyclic benznidazole. However this compound is only used in the acute phase of the disease and its effectiveness is varied in accordance with the geographical area, probably as a consequence of the variation of strains of the parasite and presents serious side effects. An interesting tool in medicinal chemistry is the use of bioisosterism for the synthesis of analogous molecules, which possess biological properties relatable generally act on the same target as pharmacological agonists or antagonists. Moreover, the reactions related to condensations of 1.3 dipolar cycloaddition catalyzed by Cu(I), involving strategies \"click chemistry\" has the strengths of the fact usually do not form byproducts, being easy to perform and present high yields. Starting from two commercial compounds benzylamine and chloro acetyl chloride) we performed the synthesis of a library of twenty-three analog compounds to benznidazole via a synthetic route short and easy to perform. Tests of trypanocidal activity involving Tulahuen strain of T. cruzi, and cytotoxicity assays.

No capítulo 1 apresentamos uma síntese eficiente de compostos 5-organoteluro-1H- 1,2,3-triazóis realizada via reação de cicloadição [3+2] entre azidas orgânicas e alquinos substituídos com organotelúrio. Além disso, os 5-organoteluro-1H-1,2,3-triazóis foram funcionalizados na posição 5 do anel triazólico por reação de acoplamento cruzado de Sonogashira. A regioquímica dos produtos de cicloadição foram descritas com base em experimentos de RMN, cálculos teóricos e cristalografia de raio-x. Apresentamos uma proposta mecanística para a cicloadição mediada por cobre, baseada em experimentos de espectrometria de massas de alta resolução. No capítulo 2, investigamos a eficiência de reações one-pot com indol, cloreto de oxalila e diferentes nucleófilos para obtermos derivados do indol-3-glioxila em condições adequadas. Do mesmo modo, envolvendo a adição de azidas orgânicas, levando à síntese de indol-3-glioxil-1,2,3-triazóis, os produtos foram obtidos com rendimentos que variaram de 59 a 85%. / In chapter 1 we present an efficient synthesis of 5-organotelluro-1H-1,2,3-triazole compounds that was accomplished via the [3+2]-cycloaddition reaction of organoazides and organotelluro alkynes. Additionally, 5-organotelluro-1H-1,2,3-triazoles were readily functionalized at the 5-position via the Sonogashira cross-coupling reaction, leading to highly functionalised triazoles. The regiochemistry of the products was assessed by bidimensional NMR experiments, theoretical calculations and x-ray crystallography. We presented a mechanistic proposal for the cycloaddition mediated by copper, based on high resolution mass spectrometry experiments. In chapter 2 we investigated a general and efficient reaction of indole with oxalyl chloride and nucleophiles providing indole-3-glyoxyl derivatives which has been developed in mild conditions. In the same fashion, the other reaction involved the addition of organic azides leading to the synthesis of indole-3-glyoxyl-1,2,3-triazoles, which proceeds smoothly generating the products in moderate to high yields.

No capítulo 1 apresentamos uma síntese eficiente de compostos 5-organoteluro-1H- 1,2,3-triazóis realizada via reação de cicloadição [3+2] entre azidas orgânicas e alquinos substituídos com organotelúrio. Além disso, os 5-organoteluro-1H-1,2,3-triazóis foram funcionalizados na posição 5 do anel triazólico por reação de acoplamento cruzado de Sonogashira. A regioquímica dos produtos de cicloadição foram descritas com base em experimentos de RMN, cálculos teóricos e cristalografia de raio-x. Apresentamos uma proposta mecanística para a cicloadição mediada por cobre, baseada em experimentos de espectrometria de massas de alta resolução. No capítulo 2, investigamos a eficiência de reações one-pot com indol, cloreto de oxalila e diferentes nucleófilos para obtermos derivados do indol-3-glioxila em condições adequadas. Do mesmo modo, envolvendo a adição de azidas orgânicas, levando à síntese de indol-3-glioxil-1,2,3-triazóis, os produtos foram obtidos com rendimentos que variaram de 59 a 85%. / In chapter 1 we present an efficient synthesis of 5-organotelluro-1H-1,2,3-triazole compounds that was accomplished via the [3+2]-cycloaddition reaction of organoazides and organotelluro alkynes. Additionally, 5-organotelluro-1H-1,2,3-triazoles were readily functionalized at the 5-position via the Sonogashira cross-coupling reaction, leading to highly functionalised triazoles. The regiochemistry of the products was assessed by bidimensional NMR experiments, theoretical calculations and x-ray crystallography. We presented a mechanistic proposal for the cycloaddition mediated by copper, based on high resolution mass spectrometry experiments. In chapter 2 we investigated a general and efficient reaction of indole with oxalyl chloride and nucleophiles providing indole-3-glyoxyl derivatives which has been developed in mild conditions. In the same fashion, the other reaction involved the addition of organic azides leading to the synthesis of indole-3-glyoxyl-1,2,3-triazoles, which proceeds smoothly generating the products in moderate to high yields.

A tripanossomíase sul-americana, também conhecida como Doença de Chagas é uma enfermidade endêmica da América Latina.A doença é causada pelo protozoário Trypanosoma cruzi, cuja transmissão em seres humanos e outros mamíferos ocorrem, principalmente, através das fezes do inseto \"barbeiro\" (triatoma infestans) infectado.Desde a descoberta já foram realizadas inúmeras tentativas de tratamento sem obter quimioterapia eficaz. Hoje o tratamento é realizado pelo uso do fármaco nitroheterocíclico benznidazol. Porém esse composto só é utilizado na fase aguda da doença e tem sua eficácia variada de acordo com a área geográfica, provavelmente como consequência de variação de cepas do parasita e apresenta graves efeitos colaterais. Uma ferramenta interessante em Química Medicinal é o uso do bioisosterismo para a síntese de moléculas análogas, que por possuírem propriedades biológicas relacionáveis geralmente atuam no mesmo alvo farmacológico como agonistas ou antagonistas. Por outro lado, as reações relacionadas às condensações de cicloadição 1,3 dipolar catalisadas por Cu(I), envolvendo estratégias de \"click chemistry\" tem como pontos positivos o fato de geralmente não formarem subprodutos, serem de fácil execução e apresentarem rendimentos elevados. Partindo de dois compostos comerciais (benzilamina e cloreto de cloro acetila) efetuou-se a síntese de uma biblioteca de vinte e três compostos análogos ao benznidazol através de uma rota sintética curta e de fácil execução. Foram realizados ensaios de atividade tripanocida envolvendo a cepa Tulahuen de T.cruzi, bem como ensaios de citotoxicidade. / The South American trypanosomiasis, also known as Chagas\' disease is an endemic disease in Latin America. The disease is caused by the protozoan Trypanosoma cruzi, whose transmission in humans and other mammals occur primarily through the faeces of the insect \"barbeiro\" (triatoma infestans) infection. Since the discovery already been carried out many attempts to obtain effective chemotherapy treatment. Today\'s treatment is accomplished through the use of the drug nitro-heterocyclic benznidazole. However this compound is only used in the acute phase of the disease and its effectiveness is varied in accordance with the geographical area, probably as a consequence of the variation of strains of the parasite and presents serious side effects. An interesting tool in medicinal chemistry is the use of bioisosterism for the synthesis of analogous molecules, which possess biological properties relatable generally act on the same target as pharmacological agonists or antagonists. Moreover, the reactions related to condensations of 1.3 dipolar cycloaddition catalyzed by Cu(I), involving strategies \"click chemistry\" has the strengths of the fact usually do not form byproducts, being easy to perform and present high yields. Starting from two commercial compounds benzylamine and chloro acetyl chloride) we performed the synthesis of a library of twenty-three analog compounds to benznidazole via a synthetic route short and easy to perform. Tests of trypanocidal activity involving Tulahuen strain of T. cruzi, and cytotoxicity assays.

Les interactions sucre-lectine jouent un rôle très important dans de nombreux processus biologiques comme les infections par des virus ou des bactéries. Toutefois, ces interactions étant faibles, la présentation de manière multivalente des résidus saccharidiques est nécessaire pour obtenir une augmentation significative des constantes d'association. Une technique basée sur l'utilisation de glycooligonucléotides et d'une puce à ADN utilisée comme plateforme d'ancrage a permis d'étudier l'affinité d'un grand nombre de composés envers les lectines PA-IL et PA-IIL de Pseudomonas aeruginosa et la lectine BambL de Burkholderia ambifaria. Les glycooligonucléotides ont été synthétisés, à partir de blocs de construction synthétisés en aval, en utilisant la chimie des acides nucléiques supportée et automatisée (phosphoramidites et H-phosphonate) ainsi que des réactions de « click chemistry » (la cycloaddition 1,3-dipolaire catalysée par le cuivre (I) ou le couplage thiol par addition de type Michael ou par substitution nucléophile d'un dérivé bromoacetamide).Les glycoclusters ayant montrés une bonne affinité envers les lectines cibles ont été sélectionnés et resynthétisés en solution sans l'étiquette ADN à l'échelle de la centaine de milligrammes. Les glycoclusters ainsi synthétisés en deux ou trois étapes avec une seule purification ont pu être évalués par quatre techniques d'analyse des interactions (HIA, ELLA, SPR et ITC) en présence des lectines PA-IL, PA-IIL et BambL. Nous avons trouvé un tétragalactocluster et un tétrafucocluster possédant une forte affinité envers la lectine PA-IL et BambL respectivement avec des valeurs de Kd de 157 nM et 43 nM. / Carbohydrate-lectin interactions play a key role in various biological processes such as infection by viruses or bacteria. As these interactions are weak, the multivalent association of carbohydrate is necessary to increase the binding constant. We used glycooligonucleotide and DNA chip to study the affinity of diverse compounds to PA-IL and PA-IIL lectins of Pseudomonas aeruginosa and Bambl lectin of Burkholderia ambifaria. Glycooligonucleotides were synthesized with previously prepared building blocks, using automated supported nucleic acid chemistry (phosphoramidites and H-phosphonate) and “Click chemistry” (copper (I) catalyzed 1,3-dipolar cycloaddition, thiol coupling by Michael addition and nucleophilic substitution of bromoacetamide derivative).Glycoclusters showing the better affinities toward the lectins have been synthesized to a hundred milligrams scale in solution without the DNA tag. The synthesis processes in two or three steps and only one final purification. Their interactions with the lectins PA-IL, PA-IIL and BambL were studied by several assays (HIA, ELLA, SPR and ITC). A tetragalactocluster and a tetrafucocluster showed high affinity toward respectively the lectin PA-IL (Kd = 157 nM) and the lectin BambL (Kd = 43 nM).

L'utilisation de la réaction de cycloaddition 1,3 de Huisgen afin d'optimiser les propriétés de polymères fluorés constitue l'objectif de ce travail. Cette cycloaddition a été étudiée selon deux stratégies spécifiques. La première consiste en une cycloaddition, réalisée entre un groupe azidé et une fonction nitrile, non catalysée, tandis que la seconde concerne la cycloadditon, catalysée par le cuivre, entre un groupe azido et une fonction alcyne dont la réaction est classiquement appelée « click chemistry ». Le premier chapitre est consacré à une étude bibliographique sur la réticulation et la post-réticulation chimiques des polymères à température ambiante et à des températures inférieures à 150 °C. Cette étude décrit de façon quasi-exhaustive les différentes réactions chimiques permettant de réaliser une réticulation, et ce en les classant par fonctions clés. Le second chapitre décrit la réticulation d'un élastomère fluoré commercial, porteur de fonction nitrile par cycloaddition 1,3 de Huisgen non catalysée à l'aide d'un agent réticulé fluoré téléchélique bisazidé. Une étude modèle de la réaction de cycloaddition mettant en jeu une réaction nitrile-azide à l'aide de composés moléculaires afin de déterminer les meilleures conditions de réaction. Le troisième chapitre concerne le greffage d'un composé phthalocyanine sur un copolymère fluoré (de type poly(chlorotrifluoéthylène-co-2-iodoethyl vinyl éther) par cycloaddition de Huisgen catalysée au cuivre, ou « click chemistry », dans le but d'obtenir un composé possédant des propriétés photovoltaïques intéressantes. / The objective of this work deals with the Huisgen 1.3 cycloaddition reaction to optimize the properties of fluoropolymers. This cycloaddition is investigated using two main strategies. The first one concerns a cycloaddition performed between an azide group and a nitrile function, and non-catalyzed, while the second one is a copper-catalyzed cycloadditon, involving a group azide and an alkyne function and this reaction is conventionally called "click chemistry". The first chapter is devoted to a non-exhaustive literature review on the chemical crosslinking and post-crosslinking polymers carried out at room temperature and at temperatures below 150 ° C. This study describes a list of different chemical reactions to achieve a crosslinking, and that classifying them by key functions. The second chapter describes the crosslinking of commercially available, fluoroelastomer, bearing nitrile groups by 1,3 Huisgen uncatalyzed cycloaddition using a telechelic fluorintaed bisazido crosslinking agent. This chapter exhibits first a model study of the cycloaddition involving a nitrile-azide reaction to determine the best reaction conditions. The third chapter concerns the grafting of an alkyne phthalocyanine compound onto a fluorinated copolymer (poly(chlorotrifluoethylene-co-2-iodoethyl vinyl ether) by 1,3 Huisgen cycloaddition catalyzed by copper, or "click chemistry", to obtain a compound having good photovoltaic properties.

Ce travail a pour objet l'obtention et la caractérisation de nouveaux copolymères amphiphiles et d'hydrogels à hydrophilie contrôlée, à partir de polymères naturels, avec comme utilisations potentielles la vectorisation de principes actifs. En conséquence, il est donc nécessaire que les polymères utilisés pour l’obtention de ces architectures répondent à un certain nombre de contraintes, notamment être non-toxiques, biocompatibles et biodégradables. Pour ces raisons, on retient le plus souvent comme matériaux de départ des polymères naturels, en particulier les polysaccharides. Quelques polymères synthétiques répondent aussi à ces contraintes, telle que la polycaprolactone. Ainsi, le matériau de base utilisé dans ce travail est l'amidon sur lequel a été greffé soit la poly (ε-caprolactone), soit une chaîne grasse. La thèse est structurée en cinq chapitres consacrés d'une part au greffage de structures hydrophobes sur l'amidon et la formation d'hydrogels à hydrophobie modulable, d'autre part à la vectorisation de la lévofloxacine par ces composés. La première partie traite du greffage de la polycaprolactone sur l'amidon par "click chemistry" (CuAAC) entre l’amidon fonctionnalisé par des fonctions alcynes et des polycaprolactones à fonction azoture en bout de chaîne, ces dernières étant préalablement obtenues par POC de la caprolactone. Les réactions de CuAAC ont été effectuées non seulement selon les protocoles habituels, mais aussi par micro ondes. Par ailleurs, l'amidon a aussi été hydrophobisé par les méthodes usuelles d'estérification par une chaîne grasse via le chlorure de l’acide palmitoique. Les produits ainsi obtenus ont été caractérisés par RMN, IR, XPS et leur comportement dans différents solvants (solubilité, gonflement) a été étudié. Une seconde partie est consacrée à l'élaboration d'hydrogels à base d’amidon et d’amidon modifié avec des chaînes d’acides gras et de PCL par réticulation avec l’acide citrique. Afin d'atteindre les objectifs, une stratégie multifactorielle expérimentale avec deux variables indépendantes a été utilisée. La modélisation mathématique des données expérimentales permet de remonter aux paramètres physico-chimiques pertinents, montre les effets de synergie et établit les conditions d'optimisation. Une dernière partie a permis d'évaluer les cinétiques de libération de la lévofloxacine, un antibiotique de dernière génération, par les hydrogels obtenus. Les matériaux obtenus ont montré des propriétés de libération contrôlée potentiellement intéressantes. Les résultats obtenus au cours de cette thèse ont été évalués par la publication de trois articles et par dissémination des résultats au six conférences internationales. / This work is part of a current field that has grown steadily in recent years and aims to obtain and characterize amphiphilic polymers and hydrogels with controlled hydrophilicity, derived from natural polymers, with potential use as controlled drug delivery systems. Acting in contact with the body or inside it, it is necessary that the polymers used to obtain these architectures meet a number of constraints to be non-toxic, biocompatible and biodegradable. For these reasons, most of the time natural polymers are chosen, especially those from the class of polysaccharides, but there are also synthetic polymers that meet these requirements. Thus, the materials considered were: starch, poly (ε-caprolactone), palmitoyl chloride, citric acid, their by-products of degradation being non toxic. The thesis is divided into two parts, one theoretical and one experimental, and structured into five chapters, wherein: the first chapter is the theoretical and the others, the original, experimental part. In a first time, starch was hydrophobized by grafting poly-caprolactone using "click chemistry" (CuAAC) (using the traditional way and the one using the microwaves) between starch chains bearing alkyne side functions and polycaprolactone chains with azide chain end function, these latter being synthesized by ROP of caprolactone. Another way consists in the esterification with long fatty acid chains. Physico-chemical analysis, morphological and the behavior in different solutions have been made to obtain information about both the structure and the characteristics of the products. in a second part, hydrogels based on starch and modified starch with fatty acid chains or PCL and crosslinked with citric acid have been obtained. To achieve the objectives, a strategy with two experimental independent variables was used, the mathematical modeling of experimental data giving information on the existing phenomena, and showing the synergistic effects and at the same time establishing the conditions for optimization. After evaluation of the kinetics of controlled release of levofloxacin, an antibiotic, from the synthesized hydrogels, the materials based on modified starch have shown to present sustained release properties superior in terms of slowing release, a feature that recommends them successfully in the pharmaceutical and cosmetics applications. The results obtained in this thesis have been evaluated by the publication of three articles and dissemination of results at six international conferences.