Les nanocomposites à base de polymères sont utilisés depuis plusieurs années dans différents domaines industriels. Ils permettent une amélioration des propriétés des polymères et/ou l'accès à certaines propriétés presque inexistantes sur le polymère de base. Cependant, les polymères utilisés sont souvent d’origine pétrochimique. Au cours des dernières années, l'accumulation de déchets toxiques a, entre autres, conduit à un remplacement progressif de ces matières par des polymères issus des agro-ressources et/ou biodégradables. Notre étude porte sur deux polymères biodégradables utilisés comme matrice dans des nanocomposites, le poly (acide lactique) (PLA) et le poly (butylène succinate) (PBS). Elle a pour but, d'une part, d’améliorer les propriétés barrière aux gaz et à la vapeur d'eau, et d'autre part, de les rendre conducteur de chaleur. Pour ce faire, deux différents types de charges ont été utilisés. La première, la montmorillonite organiquement modifiée (OMMT) a permis d’obtenir une amélioration significative des propriétés mécaniques et barrière du polymère. La seconde, le graphite expansé (EG) a prouvé sa capacité à augmenter les propriétés de transport de chaleur dans les polymères. Une étude bibliographique a révélé que les conditions de mise en œuvre et les affinités entre les deux composés influencent considérablement les propriétés finales du nanocomposite. Ainsi les conditions de mise en œuvre ont été optimisées en faisant varier le temps et les températures de mélange de même que la méthode de mise en œuvre en fonction des charges utilisées. Pour améliorer les interactions entre la matrice et les charges, ces dernières ont été fonctionnalisées par un alkoxysilane, le 3-AminoPropylTrimethoxy-Silane. Les effets de cette fonctionnalisation sur les propriétés mécaniques, barrière, thermiques et thermophysiques des nanocomposites sont présentés. Pour les nanocomposites chargés en EG, l’effet des tailles et de la distribution des tailles des particules sur les conductivités thermiques des nanocomposites a été discuté en se basant sur un modèle de type Maxwell-Garnett basé sur la théorie des champs moyen. / Polymer based nanocomposites have been used for several years in various industrial fields. They allow an improvement of the polymer properties and/or an access to some almost non-existent properties of the neat material. However, the used polymers originated mostly from petrochemical industry. In recent years, the accumulation of toxic waste, among others, led to a gradual replacement of these materials by polymers from agro-resources and/or biodegradables. Our study focuses on two biodegradable polymers used as matrix in nanocomposites, poly (lactic acid) (PLA) and poly (butylene succinate) (PBS). It aims, on one hand, to improve their barrier properties to gases and water vapor, and on the other, to make them heat conductors. To achieve this, two different kinds of fillers were used. The first one, organically modified montmorillonite (OMMT), has achieved a significant improvement in mechanical and barrier properties of the polymer. The second one, expanded graphite (EG), has proven its ability to increase heat transport properties of polymers. A literature review has revealed that the conditions of nanocomposite preparation and the affinities between the two materials greatly influence the final properties of the nanocomposite. Thus the preparation parameters were optimized by varying the melting time and temperature as well as the preparation method according to the fillers used. To improve the interaction between the matrix and the fillers, they were functionalized with an alkoxysilane, 3-aminopropyltrimethoxy-Silane. The effects of this functionalization on the mechanical, barrier, thermal and thermophysical properties of nanocomposites are presented. For EG based nanocomposites, the EG size effect and size distribution on the thermal conductivity of nanocomposites were discussed based on a theoretical model using the Maxwell-Garnett mean-field theory.

L’objectif de cette thèse est de synthétiser des nanoparticules dans des microsystèmes en copolymère d’oléfine cyclique (COC), en vue du développement d’une nouvelle phase stationnaire de chromatographie présentant des performances améliorées. Dans un premier temps, la base théorique du projet est présentée. Les performances chromatographiques d’une colonne en fonction de la taille des particules qui la constituent sont présentées, en termes de résolution et d’efficacité, ainsi qu’en temps d’analyse. L’utilisation de nanoparticules s’avère optimale, mais l’état de l’art sur les différents types de colonnes et de modes de séparations en microsystèmes montre la difficulté technique de cet objectif. Les différentes voies de synthèse de nanoparticules par polymérisation radicalaire en micro et miniémulsion sont ensuite détaillées. Les essais préliminaires ont permis de définir la méthodologie d’approche : 1) la synthèse de nanoparticules par polymérisation radicalaire en miniémulsion et 2) la fonctionnalisation indispensable des supports COC. Dans un premier temps, la composition de la miniémulsion a été optimisée par plan d’expériences. La meilleure formulation permet la synthèse, après photopolymérisation, de nanoparticules monodisperses de diamètre moyen inférieur à 200 nm. Une étude d’ancrage des nanoparticules sur plaques COC est ensuite réalisée. L’optimisation du greffage d’un monomère polyéthylène glycol diacrylate (PEGDA) est réalisée par plan d’expériences. La synthèse photochimique des nanoparticules sur des surfaces COC fonctionnalisées PEGDA permet l’obtention de nanoparticules sphériques et monodisperses de taille inférieure à 200 nm répondant parfaitement au cahier des charges. Ce travail constitue une première étape dans la réalisation de phases stationnaires innovantes en chromatographie / The aim of this thesis is the synthesis of nanoparticles in cyclic olefin copolymer (COC) microchips in order to develop a new stationary phase. The bibliography review reveals the interest of this project in increasing column performance (efficiency and resolution) and reducing the analysis time. A general review on stationary phases and separation mode in microchips is presented. The synthesis of nanoparticles by radical polymerization of micro and miniemulsion is then detailed. The preliminary results helped defining the methodological approach: 1) Synthesis of nanoparticles via miniemulsion radical polymerization and 2) functionalization of COC surfaces. First, miniemulsion composition is optimized by an experimental design. The optimal miniemulsion led, after photopolymerization, to monodisperse nanoparticles with a diameter size inferior to 200 nm. The anchorage on COC surface is then investigated and shows that COC functionalization with a hydrophilic monomer is essential. Photografting of polyethylene glycol methacrylate (PEGDA) optimization is carried out by an experimental design. The UV synthesis of nanoparticles on COC surfaces functionalized by PEGDA is demonstrated. Monodisperse and spherical nanoparticles with a diameter size inferior to 200 nm are obtained. This work is considered as a first step in the development of a new stationary phase for chromatography

Ce travail de thèse porte sur l'incorporation de charges minérales d'oxyde d'erbium, Er2O3, et d'oxyde de praséodyme, Pr6O11, dans une matrice polymère de type élastomère, ceci dans le cadre d'un projet industriel de remplacement du plomb dans des équipements de radioprotection. L'objet de cette thèse était d'améliorer la dispersion des charges au sein de la matrice par le biais de procédés de traitements chimiques de ces particules. Divers types de fonctionnalisations de surface ont été employés afin de compatibiliser celles-ci avec une matrice organique, notamment par greffage de composés de type acides phosphoniques. Plusieurs acides phosphoniques ont ainsi pu être utilisés avec succès pour la fonctionnalisation des deux types de charges. La caractérisation de ces différentes fonctionnalisations représente une part importante de ce projet. Des techniques d'analyse innovantes, aussi bien directes qu'indirectes ont été employées dans ce but, à savoir de la Py-GC/MS pour la détection des composés ancrés à la surface des charges, de la fluorescence X et de la spectroscopie infrarouge dans un objectif de quantification, mais aussi des études cinétiques de sédimentation des charges dans un milieu liquide organique. Finalement, des composites ont pu être obtenus par mélange des charges, traitées et non traitées, avec une matrice polyuréthane. Des essais de traction ont permis de montrer clairement une amélioration des propriétés mécaniques de certains des composites, grâce à la fonctionnalisation des charges par les acides phosphoniques. / This thesis focuses on the incorporation of mineral fillers of erbium oxide, Er2O3, and praseodymium oxide, Pr6O11, in an elastomeric polymer matrix, in the context of an industrial project to replace the lead in radiation protection equipment. The actual purpose of this thesis was to improve the dispersion of the fillers in the matrix through chemical treatment processes of these particles. Various types of surface functionalization were used to compatibilize them with an organic matrix, in particular by grafting compounds such as phosphonic acids. Hence, several phosphonic acids have been successfully used for the functionalization of both types of fillers. The characterization of these functionalizations is an important part of this project. Innovative analysis techniques, both direct and indirect have been used for this purpose, namely Py-GC/MS to detect the chemical compounds anchored to the surface of the fillers, X-ray fluorescence and FTIR spectroscopy with a quantification target, but also a study of sedimentation kinetics of the fillers in an organic medium. Finally, composites were obtained by mixing the fillers, untreated and treated, with a polyurethane matrix. Tensile tests have clearly shown an improvement of mechanical properties for some of the composites, due to the functionalization of the fillers by phosphonic acids.

Ce travail de thèse a pour objectif d’élaborer de nouveaux revêtements composites en utilisant les nanocristaux de cellulose (NCC) comme additifs biosourcés. Pour pallier au problème d’incompatibilité entre les charges hydrophiles et les matrices hydrophobes, une méthode simple à partir des esters de vinyle a été développée pour fonctionnaliser la surface des NCC. Une étude préliminaire réalisée à partir de l’acétate de vinyle utilisé comme réactif modèle, a d’abord permis d’optimiser les conditions de réaction. Ce protocole expérimental a ensuite été étendu à d’autres esters de vinyle fonctionnels, confirmant le caractère polyvalent de la méthode. Les NCC non modifiés et acétylés ont été dispersés dans des matrices acryliques (latex) ou polyuréthane (réticulable), afin d’étudier leur impact sur les performances mécaniques et barrières des composites. Une amélioration des propriétés mécaniques et barrières à l’oxygène a pu être observée dans certains cas, mais l’acétylation de surface des NCC n’a pas conduit à de meilleures performances. Une solution bicouches constituée d’un film 100 % NCC acétyles recouvert de polymère a alors été envisagé et a d’augmenter fortement les propriétés barrières à l’oxygène des différents matériaux. Certains NCC fonctionnalisés ont également été dispersés dans une matrice polydiméthylsiloxane, potentiellement utilisable comme revêtement protecteur pour l’aérospatial. Une amélioration notable de la stabilité thermique et optique sous irradiations UV dans des conditions géostationnaires a alors été observée. / The objective of this research work consist in the elaboration of novel compositecoatings using cellulose nanocrystals (CNC) as biobased additives. To palliate the problem ofincompatibility between the hydrophilic filler and the hydrophobic matrices, a simple methodbased on vinyl esters was developed to functionalize the CNC surface. A preliminary studyperformed with vinyl acetate selected as model reactant first allowed optimizing the reactionconditions. This experimental protocol was subsequently extended to other functional vinylesters to confirm the versatility of the method. The unmodified and acetylated CNC weredispersed in acrylic polymers (latex) or polyurethane (cross-linked resin) matrices, to studytheir impact on the mechanical and barrier performances of the composites. An improvementof the mechanical and barrier properties could be observed in some cases, but the CNCacetylation did not improve further the performances. A bi-layer approach consisting in afilm of 100 % of acetylated CNC coated with the polymer was then envisaged, and allowedincreasing significantly the oxygen barrier properties of the different resins. Some of thefunctionalized CNC were incorporated into a polydimethylsiloxane matrix, for a potential useas protective aerospace coating. A significant improvement in thermal stability and in opticalstability under UV irradiation in geostationary conditions was then observed.

Les nanotubes de carbone ou le graphène sont des formes allotropiques du carbone prometteuses pour un large domaine d’applications, mais des modifications de leur surface carbonée sont nécessaires pour leur manipulation et mise en forme. La fonctionnalisation covalente est un des moyens utilisés avec succès dans ce cadre, même si les modifications induites ne sont pas contrôlables. Les travaux réalisés au cours de cette thèse concernent l’utilisation de la réduction chimique des nanotubes et autres nanoformes de carbone, nanocornes, graphène ou nanodisques, pour d’une part obtenir des solutions stables et concentrées dans une gamme de solvants dépendant du type de nanoforme et d’autre part fonctionnaliser de manière covalente les différents types de surface carbonée de ces objets. Dans le cas des nanotubes, des molécules acceptrices ou donneuses d’électrons ont ainsi été greffées permettant la formation d’ensembles donneur-accepteur. D’autre part, le nombre de fonctions chimique greffées a pu être contrôlé, préservant ainsi les propriétés électroniques des nanotubes. / Carbon nanotubes and graphene are promising allotropes of carbon for a large range of applications. Due to their tendency to aggregate, modifications of the carbon surface are required in order to manipulate them. Covalent functionalization is one of the ways commonly used to reach this target even if this route is not controllable. The study presented in this thesis deals with the chemical reduction of carbon nanotubes and other forms of carbon such as nanohorns, graphene, nanocones and nanodisks. Two main results have been demonstrated here. First, adding electrons to these materials renders them soluble at high concentrations in various organic solvents. Second, these reduced materials can be functionalized covalently thanks to the charges excess. Donor-acceptor dyads have thus been prepared by grafting organic dyes such as porphyrin and perylene to the nanotubes. Furthermore the extent of functional groups can be controlled preserving the electronic properties of carbon nanotubes.

This thesis discusses methods for the comparatively mild covalent functionalization of graphene. Several graphene models were investigated: polycyclic aromatic hydrocarbons (PAHs), chemical vapor deposition (CVD)-graphene on SiO2/Si substrate, graphite foil, graphite flakes, kish graphite and highly oriented pyrolytic graphite. The PAHs were viewed as graphene edge analogs with the following molecules representing different edge motifs: pyrene, perylene, benzo[a]pyrene, benzo[e]pyrene, triphenylene, acenapthylene, and anthracene. Ozone was used in combination with different solvents to functionalize PAHs, graphite, and CVD-graphene on SiO2/Si. Ozonation in water or methanol resulted in trapping of the carbonyl oxide intermediate that was formed in the reaction, producing a variety of functional groups. Ozonation in hydrogen peroxide solution with sonication promoted radical formation, possibly resulting in edge-oxidation of graphite. The regioselectivity for addition reactions (ozonolysis) and electrophilic aromatic substitution reactions with graphene edges is discussed. To achieve functionalization of the basal plane of graphite or graphene, white light irradiation was used in combination with several transfer hydrogenation reagents. Formic acid treatment under irradiation resulted in the expected hydrogenation, whereas iso-propanol treatment resulted in iso-propanol attachment to the graphene. The developed methods provide opportunities for graphene functionalization without the need for metal based reagents or harsh conditions.

Part 1: Transition-metal-catalyzed direct transformations of aromatic C-H bonds are emerging as valuable tools in organic synthesis. These reactions are attractive because of they allow for inherently efficient construction of organic building blocks by minimizing the pre-activation of substrates. Of these processes, direct arylation has recently received much attention due to the importance of the biaryl core in medicinal and materials chemistry. Also, alkyne hydroarylation has garnered interest because it allows for the atom-economical synthesis of functionalized alkenes directly from simple arenes and alkynes. Described in this thesis are number of advancements in these areas. First, palladium catalyzed direct arylation of azine N-oxides using synthetically important aryl triflates is described. Interesting reactivity of aryl triflates compared to aryl bromides was uncovered and exploited in the synthesis of a compound that exhibits antimalarial and antimicrobial activity. Also reported is the efficient, direct arylation enabled (formal) synthesis of six thiophene based organic electronic materials in high yields using simple starting materials. Additionally, the site-selective direct arylation of both sp2 and sp3 sites on azine N-oxide substrates is described. The arylation reactions are carried out in either a divergent manner or a sequential manner and is applied to the synthesis of the natural products, Papaverine and Crykonisine. Mechanistic investigations point towards the intimate involvement of the base in the mechanism of these reactions. Next, the rhodium(III)-catalyzed hydroarylation of internal alkynes is described. Good yields are obtained for a variety of alkynes and arenes with excellent regioselectivity for unsymmetrically substituted alkynes. Mechanistic investigations suggest that this reaction proceeds through arene metalation with the cationic rhodium catalyst, which enables challenging intermolecular reactivity. Part 2: Access to single enantiomer compounds is a fundamental goal in organic chemistry and despite remarkable advances in enantioselective synthesis, their preparation remains a challenge. Kinetic resolution of racemic products is an important method to access enantioenriched compounds, especially when alternative methods are scarce. Described in this thesis is the resolution of tertiary and secondary alcohols, which arise from ketone and aldehyde aldol additions. The method is technically simple, easily scalable, and provides tertiary and secondary alcohols in high enantiomeric ratios. A rationale for the unique reactivity/selectivity associated with (1S,2R)-N-methylephedrine in the resolution is proposed. Organocatalysis is a rapidly developing, powerful field for the construction of enantioenriched organic molecules. Described here is a complimentary class of organocatalysis using simple aldehydes as temporary tethers to perform challenging formally intermolecular reactions at room temperature. This strategy allows for the enantioselective, intermolecular cope-type hydroamination of allylic amines with hydroxyl amines. Also, interesting catalytic reactivity for dichloromethane is revealed.

Palladium-catalyzed reactions for carbon-carbon bond formation have had a significant impact on the field of organic chemistry in recent decades. Illustrative is the 2010 Nobel Prize, awarded for “palladium-catalyzed cross couplings in organic synthesis”, and the numerous applications of these transformations in industrial settings. This thesis describes recent developments in C(sp2)-C(sp3) bond formation, focusing on alkane arylation reactions and arylative dearomatization transformations. In the first part, our contributions to the development of intramolecular C(sp3)-H arylation reactions from aryl chlorides are described (Chapter 2). The use of catalytic quantities of pivalic acid was found to be crucial to observe the desired reactivity. The reactions are highly chemoselective for arylation at primary aliphatic C-H bonds. Theoretical calculations revealed that C-H bond cleavage is facilitated by the formation of an agostic interaction between the palladium centre and a geminal C-H bond. In the following section, the development of an alkane arylation reaction adjacent to amides and sulfonamides is presented (Chapter 3). The mechanism of C(sp3)-H bond cleavage in alkane arylation reactions is also addressed through an in-depth experimental and theoretical mechanistic study. The isolation and characterization of an intermediate in the catalytic cycle, the evaluation of the roles of both carbonate and pivalate bases in reaction mechanism as well as kinetic studies are reported. Our serendipitous discovery of an arylation reaction at cyclopropane methylene C-H bonds is discussed in Chapter 4. Reaction conditions for the conversion of cyclopropylanilines to quinolines/tetrahydroquinolines via one-pot palladium(0)-catalyzed C(sp3)-H arylation with subsequent oxidation/reduction are described. Initial studies are also presented, which suggest that this transformation is mechanistically unique from other Pd catalyzed cyclopropane ring-opening reactions. Preliminary investigations towards the development of an asymmetric alkane arylation reaction are highlighted in Chapter 5. Both chiral carboxylic acid additives and phosphine ligands have been examined in this context. While high yields and enantiomeric excesses were never observed, encouraging results have been obtained and are supported by recent reports from other research groups. Finally, in part two, the use of Pd(0)-catalysis for the intramolecular arylative dearomatization of phenols is presented (Chapter 7). These reactions generate spirocyclohexadienones bearing all-carbon quaternary centres in good to excellent yields. The nature of the base, although not well understood, appears to be crucial for this transformation. Preliminary results in the development of an enantioselective variant of this transformation demonstrate the influence of catalyst activation on levels of enantiomeric excess.

Engineering of biofunctional scaffolds to precisely regulate cell behavior and tissue growth is of significance in regenerative medicine. Protein-based biomaterials are attractive candidates for functionalization of scaffold surfaces since the ability to precisely control protein sequence and structure allows for fine-tuning of cell-substrate interactions that regulate cell behavior. In this thesis, a series of de novo proteins for bio-functionalization of interfaces was designed, synthesized, and studied. These proteins are based on a diblock motif consisting of a surface-active, amphiphilic block β-sheet domain linked to a disordered, water-soluble block with a terminal functional domain. Several types of functional domains were investigated, including sequences that act as ligands for cell surface receptors and sequences that act as templates for the growth of inorganic particles. Under moderate temperature and pH conditions, the amphiphilic β-sheet block was shown to have a strong affinity to a variety of scaffold materials and to form stable protein coatings on hydrophobic materials by self-assembly. Moreover, the surface adsorption of the proteins was shown to have minimal impact on the presentation of the functional end domains in the soluble block. For the case of diblocks with the RGDS integrin binding sequence, the capability for mediating cell attachment and spreading was demonstrated via control over ligand density on hydrophobic polymer surfaces. The case of diblock proteins with templating domains for inorganic materials was investigated for two systems. First, hydroxyapatite-binding domains were ligated to the end terminus of the water-soluble block to develop proteins for possible bone regeneration applications. It was demonstrated that the hydroxyapatite-binding domain had strong affinity to hydroxyapatite nanoparticles and was able to induce calcium phosphate mineralization on the surfaces coated with diblock proteins from dilute solutions with Ca2+.and PO43-. Next, a silver-binding domain was ligated to the end terminus to create a diblock protein for potential antimicrobial surface applications. The silver-binding domain was shown to accumulate and reduce silver ions, resulting in the formation of silver nanoparticles on the surfaces functionalized by the protein.

Les SRPs (Small Rigid Platforms) sont des nanoparticules de taille inférieure à 5 nm, constituées d'une matrice de polysiloxane, à la surface de laquelle sont greffés de manière covalente des complexes de gadolinium. Les SRPs ont été développées pour des applications en imagerie multimodale, notamment en imagerie par résonance magnétique, en scintigraphie et en imagerie par fluorescence, ainsi que pour des applications en théranostic, et plus particulièrement, en radiosensibilisation. L'objectif de la thèse consiste à fonctionnaliser les SRPs par des entités de ciblage, capables d'identifier et de se lier à des récepteurs surexprimés par les tumeurs ou par l'endothélium qui leur est associé. Plus précisément, trois molécules ciblantes ont été retenues : (i) le c(RGDfK) – un pentapeptide cyclique contenant le motif Arg-Gly-Asp ciblant spécifiquement l'intégrine αuß3, récepteur de cellule endothéliale pour les protéines de la matrice extracellulaire et surexprimée par de nombreuses cellules cancéreuses, (ii) une molécule dérivée de la quinoxaline – ciblant la mélanine, sur-exprimée par de nombreux types de mélanomes (cancers de la peau), et (iii) un pyridinium – ciblant les protéoglycanes, sur-exprimés par le chondrosarcome (cancer du cartilage). Les différentes molécules ciblantes ont alors été greffées en surface des SRPs afin d'optimiser leur accumulation et leur rétention au sein des tumeurs, et par conséquent, d'augmenter le potentiel de ces SRPs en tant qu'agents théranostiques. Le couplage covalent des différents vecteurs aux SRPs et leur quantification ont été mis en évidence par diverses techniques de caractérisation physicochimiques et complémentaires. Enfin, le ciblage des nanoparticules vectorisées a été démontré par plusieurs tests in vitro et/ou in vivo lors de nombreuses collaborations pour les trois différents vecteurs / SRPs (Small Rigid Platforms) are sub-5 nanometre nanoparticles, composed of a polysiloxane network surrounded by gadolinium chelates. SRPs have previously demonstrated their efficiency for multimodal imaging and theranostic applications, especially magnetic resonance imaging, scintigraphy, fluorescence imaging, and radiosensitization. The purpose of this thesis deals with the functionalization of these SRPs by targeting entities able to recognize and to bind to receptors that are over-expressed by tumours or by the matching endothelium. More specifically, three targeting molecules drew our attention: (i) c(RGDfK) – a cyclic pentapeptide containing the Arg-Gly-Asp motif, able to target the αuß3 integrin, an endothelial cell receptor for the proteins of the extracellular matrix and frequently expressed by tumour cells, (ii) a quinoxaline derivative – targeting melanin, which is over-expressed by melanomas (skin cancers) and (iii) a pyridinium moiety – targeting proteoglycans, which are over-expressed in chondrosarcoma (cartilage cancer). The different targeting molecules were then grafted to the SRPs in order to maximize their accumulation and retention in tumours with the aim to enhance the SRP efficiency as theranostic agents. The covalent coupling of the different targeting molecules to the SRPs and their quantification were performed by various physicochemical characterization techniques. Finally, the targeting of the functionalized SRPs was highlighted by several in vitro and/or in vivo assays thanks to numerous successful collaborations