Graft polymers with a dendritic architecture (arborescent polymers) were synthesized by ???click???, anionic, and cationic grafting. Arborescent polystyrene and polybutadiene systems were synthesized by ???click??? coupling using alkyne and azide functional groups, one of which was introduced randomly on the polymer substrate, while the other functionality was located at one end of the polymer serving as side chains. The two possible combinations of randomly and end-functionalized components were investigated for both polymer systems, but the best method for polystyrene involved side chains with an azide end group and randomly acetylenated substrates; for polybutadiene, acetylene-terminated side chains and randomly azidated substrates were preferred. The end-functionalized polymers were derived from a bifunctional initiator to introduce a protected hydroxyl group, which was converted into either an azide or an acetylene functionality. Coupling of the end-functionalized side chains with the substrate polymer serving as backbone yielded a comb-branched (or G0 arborescent) polymer. Further cycles of substrate functionalization and grafting led to the subsequent (G1 and G2) generations of arborescent polymers. Linear and branched (G0 and G1) hydroxylated polystyrene derivatives, some of which served as intermediates in the synthesis of the randomly functionalized ???click??? grafting substrates, were also explored as macroinitiators for the cationic polymerization of ethyl vinyl ether. The substrates functionalized with either secondary or tertiary alcohol groups yielded the desired arborescent polystyrene-graft-poly(ethyl vinyl ether) copolymers, without formation of linear contaminant. Arborescent polybutadiene of generations G1 and G2, with different side chain molecular weights, were also synthesized by anionic coupling of living polybutadienyllithium side chains with substrates functionalized with chlorosilane groups for comparison with the ???click??? methodology.

La recherche de nouvelles molécules à activité antiparasitaire pour lutter contre les parasites responsables de maladies telles que le paludisme ou la trypanosomiase humaine africaine est un enjeu primordial car il n’existe pas de vaccin pour ces maladies qui peuvent être mortelles et qui touchent près de 1/6 de la population mondiale. Dans ce contexte, il a été observé au laboratoire que l’amélioration de l’activité des molécules sur une cible isolée ne se retrouvait pas toujours sur les parasites. Une faible entrée de la molécule dans la cellule pourrait être une des causes de ce manque de corrélation, comme cela est souvent le cas dans la recherche de molécules actives.Pour valider ou non cette cause, ces travaux de thèse ont eu pour but de concevoir, synthétiser et évaluer de nouvelles sondes fluorescentes qui permettraient de visualiser la pénétration de molécules actives dans des cellules, en nous intéressant en particulier aux parasites responsables de la maladie du sommeil et du paludisme.Notre concept se base sur le principe de la chimie « click », sans catalyseur, impliquant une fonction alcyne et un groupement azoture. Ceci est possible lorsque la fonctionalcyne est insérée dans un cycle tendu comme celui d’un cyclooctyne qui lui confère une plus grande réactivité (Strain-Promoted Alkyne-Azide Cycloaddition).Nous avons synthétisé des dérivés de la dibenzocyclooctynone, une molécule fluorescente décrite pour réagir sans catalyseur avec des azotures, de manière à obtenir des sondes à détection « on-on’ ». Ainsi, sept nouvelles sondes fluorescentes ont été obtenues, dont trois réagissent avec des azotures avec une cinétique adéquate. Les propriétés photophysiques de ces molécules ont été caractérisées et nous avons vérifié qu’elles traversent bien la membrane des protozoaires parasites que nous étudions. La fluorescence n’est observée qu’à l’intérieur du parasite.La détection d’un azoture in cellulo a été vérifiée par HPLC- MS/MS avec une des sondes.Parmi les sept cyclooctynones obtenues, une sonde forme un adduit triazole fluorescent avec une cinétique acceptable, ce qui constitue le premier exemple de sonde « on-on’ » de cette série et une véritable avancée dans la chimie bio-orthogonale. / The discovery of new molecules with antiparasitic activity is crucial today to fight against infectious diseases such as malaria and HAT since no vaccine is available to cure these diseases. In our search for new antiparasitic compounds, we observed that activity improvement on an isolated target was not seen on parasite. We suspected an ineffective entry of the molecule into the cell to be one of the reasons for these uncorrelated results.To explore this possibility, this PhD work aimed to design, synthetize and evaluate new fluorescent probes that would allow the visualization of drug entry into parasites responsible for HAT and malaria.Our concept is based on “click” chemistry that can be achieved without catalyst, between an azide and a strained alkyne like cyclooctyne (Strain-Promoted Alkyne-Azide Cycloaddition).We synthetized derivatives of dibenzocyclooctynone, a fluorescent molecule described to undergo SPAAC reaction with azides, in order to obtain “on-on’” detection probes. Seven new fluorescent probes were therefore synthetized, among which three of them displayed adequate SPAAC kinetics. Photophysical properties of these molecules were characterized and their penetration into protozoan cells was demonstrated. Fluorescence was only observed in the parasitic cytosol.In cellulo azide detection was achieved and verified by LC- MS/MS with one of our probes.One out of the seven probes formed a fluorescent triazole adduct, which constitutes the first example of an « on-on’ » probe for this series and a real progress in bioorthogonal chemistry.

L'accès à de nouvelles techniques de synthèse simples permettant l'obtention d'architectures macromoléculaires complexes et bien définies demeure un enjeu permanent. Les réactions de couplage dites " click " permettent de relever en parti ce défi et dans cette catégorie, les γ-thiolactones sont apparues comme un nouvel outil important. Dans ce contexte, nous avons développé un nouveau procédé de synthèse de mono- et bis(γ-thiolactones) fonctionnelles basé sur la chimie radicalaire des xanthates, permettant l'accès à une bibliothèque de thiolactones porteuses de groupements fonctionnels divers. La réactivité de ces molécules a été testée au travers de la réaction amine-thiol-ène avec la fonctionnalisation d'extrémités de chaînes polymères et la polymérisation par étapes. Un exemple d'utilisation de ces polymères est présenté avec la stabilisation de nanoparticule de gadolinium en milieu aqueux. Enfin, une série de thiolactones portant des groupements susceptibles de jouer le rôle d'amorceurs et d'agents de contrôle en polymérisation radicalaire par désactivation réversible ont permis l'obtention de polymères fonctionnalisés thiolactone en bout de chaîne. Ces polymères ont par la suite été utilisés dans des réactions de modifications post-polymérisation permettant l'incorporation de groupements possédant des propriétés de fluorescences par exemple. / The development of simple synthetic protocols allowing the construction of complex and well-defined macromolecular architectures remains an ongoing challenge. The so-called "click" coupling reactions make it partially possible. Among these reactions, the use of γ-thiolactones has emerged as a new important tool. In this context, we have developed a new procedure for the synthesis of functional mono- and bis(γ-thiolactones) based on the radical chemistry of xanthates, allowing access to a library of thiolactones bearing various groups. The reactivity of these molecules was tested with the amine-thiol-ene conjugation for the functionalization of polymer chain-ends and step-growth polymerization. An application of these functionalized polymers was presented with the stabilization of gadolinium nanoparticles in water. Finally, a series of thiolactone-functional initiators or control agents for reversible-deactivation radical polymerization techniques allowed us to obtain thiolactone-terminated polymers. These polymers were then used for post-polymerization modification reactions with the incorporation of a new fluorescent group for example.

Step-growth polymerization provided an effective method for the preparation of several high performance polymers. Step-growth polymerization was used for syntheses of poly(siloxane imides), polyesters, poly(triazole esters), poly(triazole ether esters), and epoxy networks. Each of these polymeric systems exhibited novel structures, and either photoreactive capabilities, or high performance properties. There is an increasing trend towards the development of photoactive adhesives. In particular these polymers are often used in flip bonding, lithography, stimuli responsive polymers, drug delivery, and reversible adhesives. The ability to tailor polymer properties carefully with exposure to light allows for very unique stimuli responsive properties for many applications. This dissertation primarily investigates photoreactive polymers for reversible adhesion for use in the fabrication of microelectronic devices. In particular cyclobutane diimide functionality within polyimides and poly(siloxane imides) and o-nitro benzyl ester functionality within polyesters acted effectively as chromophores to this end. Thermal solution imidization allowed for the effective synthesis of polyimides and poly(siloxane imides). 1,2,3,4-Cyclobutane tetracarboxylic dianhydride acted as the chromophore within the polymer backbone. The polyimides obtained exhibited dispersibility only in dipolar, aprotic, high boiling solvents such as DMAc or NMP. The obtained poly(siloxane imides) demonstrated enhanced dispersibility in lower boiling organic solvents such as THF and CHCl₃. Dynamic mechanical analysis and tensile testing effectively measure the mechanical properties of the photoactive poly(siloxane imides) and confirmed elastomeric properties. Atomic force microscopy confirmed microphase separation of the photoactive poly(siloxane imides). ¹H NMR spectroscopy confirmed formation of maleimide peaks upon exposure to narrow band UV light with a wavelength of 254 nm. This suggested photo-cleavage of the cyclobutane diimide units within the polymer backbone. Melt transesterification offered a facile method for the synthesis of o-nitro benzyl ester-containing polyesters. ¹H NMR spectroscopy confirmed the structures of the photoactive polyesters and size exclusion chromatography confirmed reasonable molecular weights and polydispersities of the obtained samples. ¹H NMR spectroscopy also demonstrated a decrease in the integration of the resonance corresponding to the o-nitro benzyl ester functionality relative to the photo-stable m-nitro benzyl ester functionality upon exposure to high-intensity UV light, suggesting photo-degradation of the adhesive. ASTM wedge testing verified a decrease in fracture energy of the adhesive upon UV exposure, comparable to the decrease in fracture energy of a commercial hot-melt adhesive upon an increase in temperature. Click chemistry was used to synthesize polyesters and segmented block copolyesters. Triazole-containing homopolyesters exhibited a marked increase (~40 °C) in Tg, relative to structurally analogous classical polyesters synthesized in the melt. However, the triazole-containing homopolyesters exhibited insignificant dispersibility in many organic solvents and melt-pressed films exhibited poor flexibility. Incorporation of azide-functionalized poly(propylene glycol) difunctional oligomers in the synthesis of triazole-containing polyesters resulted in segmented block copolyesters which exhibited enhanced dispersibility and film robustness relative to the triazole-containing homopolyesters. The segmented triazole-containing polyesters all demonstrated a soft segment Tg near -62 °C, indicating microphase separation. Dynamic mechanical analysis confirmed the presence of a rubbery plateau, with increasing plateau moduli as a function of hard segment content, as well as increasing flow temperatures as a function of hard segment content. Tensile testing revealed increasing tensile strength as a function of hard segment, approaching 10 MPa for the 50 wt % HS sample. Atomic force microscopy confirmed the presence of microphase separated domains, as well as semicrystalline domains. These results indicated the effectiveness of click chemistry towards the synthesis of polyesters and segmented block copolyesters. Click chemistry was also used for the synthesis of photoactive polyesters and segmented block polyesters. The preparation of 2-nitro-p-xylylene glycol bispropiolate allowed for the synthesis of triazole-containing polyesters, which exhibited poor dispersibility and flexibility of melt-pressed films. The synthesis of segmented photoactive polyesters afforded photoactive polyesters with improved dispersibility and film robustness. ¹H NMR spectroscopy confirmed the photodegradation of the o-nitro benzyl functional groups within the triazole-containing polyesters, which indicated the potential utility of these polyesters for reversible adhesion. Synthesis of the glycidyl ether of 2,2,4,4-tetramethyl-1,3-cyclobutane diol (CBDOGE) allowed for the subsequent preparation of epoxy networks which did not contain bisphenol-A or bisphenol-A derivatives. Preparation of analogous epoxy networks from the glycidyl ether of bisphenol-A (BPA-GE) provided a method for control experiments. Tensile testing demonstrated that, dependent on network Tg, the epoxy networks prepared from CBDOGE exhibited similar Young's moduli and tensile strain at break as epoxy networks prepared from BPAGE. Dynamic mechanical analysis demonstrated similar glassy moduli for the epoxy networks, regardless of the glycidyl ether utilized. Tg and rubbery plateau moduli varied as a function of diamine molecular weight. Melt rheology demonstrated a gel time of 150 minutes for the preparation of epoxy networks from CBDO-GE and 78 minutes for the preparation of epoxy networks from BPA-GE, with the difference attributed to increased sterics surrounding CBDO-GE. These results indicated the suitability of CBDO-GE as a replacement for BPA-GE in many applications. / Ph. D.

Lors de la production industrielle du biocarburant éthyl tert-butyl éther (ETBE), cet éther forme un azéotrope contenant 20 % d'éthanol. Comparé à la distillation ternaire utilisée pour la purification de l'ETBE, le procédé membranaire de pervaporation pourrait offrir une alternative intéressante et d'importantes économies d'énergie. Des membranes cellulosiques ont principalement été décrites pour cette application. En particulier, la sélectivité de l'acétate de cellulose (CA) était extrêmement élevée mais son flux trop faible. Dans cette thèse, différentes stratégies de greffage ont été explorées pour améliorer ses propriétés membranaires. La première a mis en œuvre la chimie "click" pour le greffage d'oligomères polylactide, conduisant à des membranes bio-sourcés originales pour cette application. Le greffage de liquides ioniques (LIs) a ensuite été étudié, initialement par chimie "click" (échec dû à des réactions secondaires) puis par une autre stratégie en 2 étapes impliquant une simple substitution nucléophile. Une seconde série de matériaux cellulosiques a été obtenue avec des LIs contenant un même anion bromure et différents cations (imidazolium, pyridinium ou ammonium) de polarité croissante. Une troisième série de nouveaux matériaux membranaires a ensuite été développée en échangeant l'anion bromure par différents anions Tf2N-, BF4-, and AcO-. Les propriétés membranaires de tous les matériaux greffés ont finalement été évaluées sur la base du modèle de sorption-diffusion, révélant que la sorption et la pervaporation étaient conjointement améliorées par les différentes stratégies de greffage développées. / During the industrial production of ethyl tert-butyl ether (ETBE) biofuel, this ether forms an azeotropic mixture containing 20 wt% of ethanol. Compared to the ternary distillation currently used for ETBE purification, the pervaporation membrane process could offer an interesting alternative and important energy savings. Cellulosic membranes have been mainly reported for this application. In particular, the selectivity of cellulose acetate (CA) was outstanding but its flux was too low. In this work, different grafting strategies were developed for improving the CA membrane properties for ETBE purification. The first strategy used "click" chemistry to graft CA with polylactide oligomers leading to original bio-based membranes for the targeted application. The grafting of ionic liquids onto CA was then investigated first by "click" chemistry (unsuccessful due to side reactions) and then by another two-step strategy implying simple nucleophilic substitution. A second series of cellulosic materials was obtained by grafting different ionic liquids containing the same bromide anion and different cations (imidazolium, pyridinium or ammonium) with increasing polar feature. A third series of new membrane materials was finally developed by exchanging the bromide anion with different anions Tf2N-, BF4-, and AcO-. The membrane properties of all grafted CA membranes were finally assessed on the basis of the sorption-diffusion model, which revealed that both sorption and pervaporation properties were improved by the different grafting strategies

<p>U ovoj doktorskoj disertaciji ispitane su 1,3-dipolarne<br />cikloadicione reakcije steroidnih azido-nitrila, nitrona i<br />nitril-oksida, pri čemu su sintetizovana različita<br />heterociklična steroidna jedinjenja androstanske i estranske<br />serije. Utvrdjene su strukture novosintetizovanih<br />jedinjenja. Ispitana je biolo&scaron;ka aktivnost odabranih<br />jedinjenja.</p> / <p>In this PhD thesis 1,3-dipolar cycloadditions of<br />steroidal azido-nitriles, nitrones and nitrile-oxide were<br />examined. Various steroidal heterocyclic compounds in<br />the androstane and estrane series were synthesised. The<br />structural characterisation of newly synthesised<br />compounds was done. Biological activity of selected<br />compounds was examined.</p>