Fluoropolymers are a versatile and attractive group of compounds having an interesting mix of properties that make them highly useful for various applications. Because of strong bonding between the carbon and fluorine atom, they exhibit unique physical and chemical properties such as high thermal stability, increased chemical resistance, low refractive index, enhanced inertness towards many solvents and hydro-compounds. These characteristics have led them to be widely used in aerospace, aeronautics, optics, microelectronics, paints and coatings, and engineering structures and as biomaterials. Amphiphilic copolymers possess unique solution and solid-state properties due to their well-defined molecular architecture. These properties arise as the result of covalently combining two thermodynamically different polymer blocks that phase separate on the nanoscale. Amphiphilic copolymers based on a fluoro-monomer will combine the favourable physiochemical properties of the desired fluorine segment in combination with complementary hydrophilic segments. Such fluorinated amphiphilic copolymers are potentially useful for drug delivery vehicles and membrane applications. This project is aimed at making fluorinated amphiphilic block copolymers of hydrophobic 2, 3, 4, 5, 6 –pentafluorostyrene (PFS) and hydrophilic methacrylic acid (MAA). A controlled radical polymerization mechanism, nitroxide mediated polymerization (NMP) using NHS-BlocBuilder as the initiator was employed. The advantage of using NMP is that it facilitates the synthesis of copolymers with well-controlled narrow molecular weight distribution. However, methacrylate homopolymerization by NMP is challenging due to the high dissociation equilibrium constant therefore, the use of PFS as a controlling comonomer was explored. We established that to obtain a controlled copolymerization, a minimum of 70 mol% PFS was required, which is significantly greater than other copolymerization systems such as using as little as 4.5-8 mol% styrene to control the copolymerization of MAA. We surmise that this lack of control is due to the unfavourable reactivity ratios (Appendix I) which favour the addition of MAA rather than PFS (rPFS = 0.012, rMAA = 8.12). However, these unique reactivity ratios suggest that a semi-batch approach can be utilized to synthesize almost pure block copolymers in one pot. Therefore, poly(PFS)–b-(PFS-ran-MAA) block copolymers were synthesized and characterized by a semi batch addition of MAA. While successful, the concentration of irreversibly terminated chains was evident and greater care in reducing these unwanted reactions needs to be addressed.

Amphiphilic block copolymers based on poly(ethylene glycol) (PEG) and poly(vinylidene fluoride) (PVDF) were synthesized by RAFT polymerization. The commercial poly(ethylene glycol) methyl ether (Me-PEG-OH, 20 Kg/mol) and difunctional polyethylene glycol (OH-PEG-OH, 20 Kg/mol) were used to synthesize diblock copolymers (Me-PEG-b-PVDF), and triblock copolymers (PVDF-b-PEG-b-PVDF) respectively. For the synthesis, the esterification reaction followed by the SN2 reaction was employed to make macro CTA (Me-PEG-XA, XA-PEG-XA, XA refers to the xanthate group). The macro CTAs were used further for VDF polymerization in dimethyl carbonate (DMC) inside the autoclave. Different molecular weights of the PVDF block (whether in the diblocks or the tribolcks) were obtained based on changes in the reaction time. The resulting block copolymers were molecularly characterized by FT-IR, 1H,19F-NMR, and SEC. The thermal properties were studied by DSC and TGA. Furthermore, the crystalline phase characterization was investigated by XRD and FT-IR. Being the obtained block copolymers are amphiphilic, their self-assembly was achieved by nanoprecipitation in DMF/water, and they were analyzed by DLS and TEM.

The synthesis of a variety of novel functionalized polymers using living polymerization techniques to achieve functional and stimuli responsive coatings on silica surfaces are described. Since microscopic features on a surface influence the overall wetting properties of the surface, a systematic investigation of the influence of polymer architecture on the microscopic characteristics of the modified surfaces was studied using silane-functionalized linear and novel star-branched polystyrene (PS). Star-branched modifiers provide functional and relatively well-defined model systems for probing surface properties compared to ill-defined highly branched systems and synthetically challenging dendrimers. Using these simple star-shaped macromolecules it was shown that the topographies of the polymer-modified surfaces were indeed influenced by the polymer architecture. A model explaining the observed surface features was proposed. A living polymerization strategy was also used to synthesize centrally functionalized amphiphilic triblock copolymers. The amphiphilic copolymers exhibited stimuli responsive changes in surface hydrophobicity. In spite of multiple solvent exposures, the copolymer films remained stable on the surface indicating that the observed changes in surface properties were due to selective solvent induced reversible rearrangement of the copolymer blocks. The chemical composition of the copolymers was tailored in order to tune the response time of the surface anchored polymer chains. Thus, the polymer coatings were used to reversibly change the surface polarities in an on-demand fashion and could find possible applications as smart adhesives, sensors and reusable membrane devices. In contrast to the afore-mentioned covalent modification approach, which often leads to permanent modification of surfaces, renewable surfaces exhibiting "universal" adhesion properties were also obtained through non-covalent modification. By employing hydrogen bonding interactions between DNA bases, surfaces functionalized with adenine groups were found to reversibly associate with thymine-functionalized polymers. This study describing the solvato-reversible polymer coating was the first demonstration on silica surfaces. A systematic investigation of the influence of surface concentration of the multiple hydrogen bonding groups and their structure on the extent of polymer recognition by the modified surfaces is also discussed. / Ph. D.

Ce travail de thèse concerne l’étude de dispersions de nanotubes de carbone (NTC) dans une matrice polymère afin d’obtenir des matériaux nanocomposites avec des propriétés améliorées. Dans la première partie, nous nous sommes intéressés à l’enrobage des NTC par des copolymères à blocs amphiphiles afin de faciliter la dispersion en solution aqueuse. L’influence de la structure chimique, de la composition et de la masse molaire des copolymères sur les propriétés a été étudiée. Dans une deuxième partie, l’incorporation des NTC dans une matrice polymère a été développée. Des procédés par voie aqueuse et par voie fondue ont été choisis afin de contrôler la répartition des NTC dans une matrice modèle de polyoxyde d’éthylène ainsi que dans des de polyéthylène ou de polyméthacrylate de méthyle. L’étude des propriétés physiques, notamment rhéologiques et électriques des nanocomposites à renfort de nanotubes a été réalisée. Ainsi les relations entre l’état des dispersions, la nature de l’enrobage et le mode d’élaboration des composites ont été établies. / This work is concerned with the study of carbon nanotubes (CNT) dispersions in a polymer matrix in order to obtain nanocomposite with unique properties. In the first part, we investigated the CNT wrapping by amphiphilic block copolymers to facilitate their suspension in aqueous solution. Based on the results, we could assess the effect on CNT dispersion quality of the molar mass of copolymers, the nature of the hydrophobic block and the length of hydrophilic block. In the second part, the incorporation of CNTs in polymer matrix was developed. Water or melt processing were chosen to control the distribution of CNTs in various polymer matrices (Polyethylene oxide, polyethylene and polymethyl methacrylate) through a prior wrapping of CNT. The studies of physical properties, including rheological and electrical properties, of nanocomposites were undertaken. Relationships between the state of dispersion, the nature of the coating and the method of preparation of composites were established.

The present work is dealing with the first synthesis and characterisation of amphiphilic diblock copolymers bearing b-dicarbonyl (acetoacetoxy) chelating residues. Polymers were obtained by Group Transfer Polymerisation (GTP)/acetoacetylation and controlled radical polymerisation techniques (RAFT).<br><br>Different micellar morphologies of poly(n-butyl methacrylate)-block-poly[2-(acetoacetoxy)ethyl methacrylate] (pBuMA-b-pAEMA) were observed in cyclohexane as a selective solvent. Depending on the block length ratio, either spherical, elliptical, or cylindrical micelles were formed. The density of the polymer chains at the core/corona interface is considerably higher as compared to any other strongly segregating system reported in the literature. It is demonstrated that there are H-bond interactions existing between acetoacetoxy groups, which increase the incompatibility between block segments. In addition, such interactions lead to the formation of secondary structures (such as b-sheets or globular structures) and larger superstructures in the micrometer length scale.<br><br>Block copolymers were also used to solubilise metal ion salts of different geometries and oxidation states in organic media, in which are otherwise insoluble. Sterically stabilised colloidal hybrid materials are formed, i.e. monodisperse micelles having the metal ion salt incorporated in their core upon complexation with the ligating pAEMA block, whereas pBuMA forms the solvating corona responsible for stabilisation in solution. Systematic studies show that the aggregation behaviour is dependent on different factors, such as the tautomeric form of the beta-dicarbonyl ligand (keto/enol) as well as the nature and amount of added metal ion salt.

L'objectif de cette thèse, la production et la caractérisation de nanovéhicules de morphologies différentes propres au traitement et au diagnostic par radio-isotopes, a conduit à une meilleure compréhension de la façon dont ces véhicules se forment. Les résultats ont permis de concevoir des méthodes de préparation novatrices qui permettent d'obtenir des échantillons de qualité supérieure à ce qui est actuellement l'état de l'art. Un nouveau procédé pour la préparation d'échantillons pour les essais de flexion de microscopie à force atomique a été développé. Cela a permis de mesurer le module d'élasticité de nanofils préparés avec des mélanges copolymère séquencé/homopolymère de composition variable. Enfin, les nanoparticules de morphologies sphérique et allongée ont été comparées dans des études in vivo réalisées avec des souris saines. Les résultats montrent que leur temps de circulation et leur biodistribution peuvent être modulés par leur taille et leur morphologie. / This thesis provides an overview of the formation, characterization and testing of micelles of different morphology for biological applications. One major aspect of this thesis is the understanding of the processes which lead to the formation of block copolymer micelles through the emulsion evaporation method. The results obtained made it possible to develop an innovative micelle formation technique which provides samples which are of superior quality to what the current state of the art. A new method has been developed for the preparation of samples for three point bending tests experiments performed by atomic force microscopy. This has made it possible to determine the elastic modulus of elongated micelles formed with various blends of homopolymers and copolymers. Finally, the behavior of spherical and elongated micelles was compared in vivo in healthy mice. The results have shown that the micelle size and morphology influences their biodistribution and circulation time.

This doctoral thesis is dedicated to the synthesis and characterization of novel functionalized hybrid structures for biomedical purposes. Systems reported in this work can be subdivided into the two main groups: natural-based materials and synthetic amphiphilic block copolymers. Both groups were studied as perspective theranostic agents for medical applications. In the first group, natural polysaccharides glycogen and mannan were selected as starting materials for preparation of novel nanoconjugates that possess ability for multimodal detection in vivo. Because grafting of natural macromolecules with synthetic polymers generally slows down the biodegradation rate, both polysaccharides were modified in two different ways to form nanoprobes with or without poly(2-methyl-2-oxazoline)s chains. The prepared nanoconjugates were functionalized with N-hydroxysuccinimide-activated fluorescence and magnetic resonance imaging labels. The resulting materials were tested both in vitro and in vivo and were shown to be completely biocompatible, biodegradable and exhibit some extra benefits in terms of their practical usage in biomedicine. Glycogen was functionalized with allyl and propargyl groups with following freeze-drying from aqueous solutions to form nano- and microfibrous materials. The presence of both...

Amphiphilic block copolymers are unique macro-molecules capable of self-assembling into bilayers analogous to naturally occurring lipid membranes. When combined with lipids, these copolymers form hybrid membranes with unique and sometimes unpredictable properties, including increased chemical and mechanical stability. These synthetically enhanced biological structures represent a versatile platform suitable for a wide range of applications, from advanced biosensing devices to drug delivery systems. The realization of these advancements necessitates a deep understanding of material properties, including the ability to predict and control interfacial behaviors. It has been shown that in the case of pure lipid membranes, interfacial behaviors are dominated by electrostatic forces. The following work will demonstrate that, electrostatic forces also represent a major driving force behind hybrid vesicle adhesion events, such as the formation of supported bilayers or interactions with biological tissues. These electrostatic forces can be manipulated to a limited degree by adjusting suspension buffer pH which primarily modulates the substrate zeta potential. Protonation of silanol groups, in the case of silicate surfaces at low pH, results in slightly positive surface zeta potential. Unfortunately, hybrid vesicles containing BdxEOy polymers exhibit a slight negative zeta potential independent of buffer pH conditions. Therefore, pH mediation can only result in supported bilayer formation in limited cases and may be insufficiently robust for many demands of application. Furthermore, the zeta potential of hybrid vesicles is surprisingly difficult to predict and control, likely due to screening and steric effects of the PEO block. This investigation provides a model to tune and control the zeta potential of such vesicles, independent of other tunable properties. This technique, in combination with pH mediation, proves to be especially effective in controlling vesicle-substrate interaction. Furthermore, translating this understanding to interactions with tissues, could facilitate more targeted drug delivery, potentially avoiding sensitive tissues, thus reducing off-target effects. In summary, this work deepens our understanding of the complex relationship between surface-potential, pH conditions, and vesicle behavior, paving the way for novel applications in bio-sensing, drug delivery, and nanotechnology.

Die vorliegende Arbeit beschreibt das Verhalten von Polypeptid-Blockcopolymeren in der festen Phase und in selektiven Lösungsmitteln. Blockcopolymere auf Basis von Poly(L-glutaminsäure-5-benzylester) (PBLGlu) oder Poly(N&#949;-benzoyloxycarbonyl-L-lysin) (PZLLys), die in dieser Arbeit eingesetzt wurden, besitzen wegen ihrer helikalen Sekundärstruktur eine sog. Stäbchen-Knäuel-Geometrie, wobei die Knäuelkomponente Polystyrol oder Polybutadien ist. Die Phasenbildung dieser Blockcopolymere ist durch die Packungseigenschaften des rigiden Blocks beeinflusst. Es wurden bevorzugt lamellare Strukturen gebildet, in denen die Stäbchen parallel angeordnet sind. Das Vorhandensein eines permanenten Dipolmomentes führt zur Wechselwirkung zwischen den Helices und zur Erhöhung des Ordnungsgrades in der Phase. Ein zusätzlicher Parameter, der die Morphologie der Phase beeinflußt, ist die Chiralität der Peptidhelix, durch die chirale Überstrukturen induziert werden. In dünnen Filmen (40 nm), wo die Geometrie begrenzt ist, führt es zu Frustrationen in der Phase. Die dadurch entstandene Spannung wurde durch einen zick-zack-artigen Lamellenverlauf abgebaut. In selektiven Lösungsmitteln für die synthetische Komponente (PS) bilden die Polypeptid-Blockcopolymere vesikuläre Strukturen, deren kugel- oder wurmförmige Geometrie von der Elastizität der Membran abhängig ist. Durch Entfernung der Z-Schutzgruppe kann PZLLys in eine wasserlösliche Form überführt werden, so dass die PB-PLLys Blockcopolymere unter Bildung von Vesikeln in Wasser löslich sind. Dabei ist die Konformation des Peptids vom pH-Wert des Mediums abhängig und kann von einem Knäuel zu einer Helix reversibel geschaltet werden. Beim Modifizieren der Sekundärstruktur wurde eine Änderung der Aggregationszahl beobachtet. Somit können diese Blockcopolymere für die Herstellung von schaltbaren Aggregaten eingesetzt werden. / The presented work describes the behaviour of polypeptide-blockcopolymers in the solid-state and well as in selective solvents. Blockcopolymers consisting of PBLGlu or PZLLys / which have been utilized in this work, possess, because of their helical structure, a so-called Rod-Coil Geometry, where the coil component consists of polystyrene or polybutadiene. The phase morphology of these block copolymers is dominated by the packing properties of the rigid blocks. Most commonly, lamellar structures were formed, where the rods were ordered in a parallel fashion. The presence of a permanent dipole moment leads to an interaction between the helices and to an increase in the degree of order within the phase. An additional parameter that influences the phase morphology is the chirality of the peptide helix, which induces the formation of chiral superstructures. In thin films (40 nm), where the geometry is limited, a disordering within the phase is observed. The resulting tension leads to the formation of a zig-zag lamellar pattern. In selective solvents of the synthetic component (PS) of the blockcopolymer, formation of vesicular structures are observed, with spherical or worm-like geometry, depending on the elasticity of the membrane. Through removal of the z-protective groups, PZLLys becomes soluble in water, through the formation of PB-PLLys blockcopolymer vesicles. The conformation of the peptide is dependent on the pH value of the medium and can be reversibly changed from a coil to a helix structure. Through modification of the secondary structure, a change in the aggregation number is observed. Thereby, these blockcopolymers may find application in the fabrication of switchable aggregates.

Ces travaux décrivent la synthèse de nanoparticules stabilisées par des polyélectrolytes d’originesynthétique (poly(acide (méth)acrylique)) ou naturelle (alginate) par polymérisation radicalairecontrôlée (PRC) de type RAFT en émulsion. Ce procédé est basé sur l’utilisation d’un polymèrehydrophile obtenu par RAFT (macroRAFT) qui est réactivé dans l’eau pour la polymérisation d’unmonomère hydrophobe. Des copolymères à blocs amphiphiles sont ainsi générés et s’auto-assemblent in situ pour former des nanoparticules. Dans un premier temps, nous avons cherché à conduire l’ensemble du procédé en milieu aqueux. Des études ont ainsi été menées sur la polymérisation RAFTdans l’eau de l’acide acrylique et de l’acide méthacrylique. Des homopolymères bien définis ont été obtenus sur une large gamme de conditions, puis ont été utilisés comme macroRAFTs pour la polymérisation en émulsion de monomères hydrophobes. Des nanoparticules stables constituées de copolymères à blocs amphiphiles bien définis ont été produites. Il a été montré que le contrôle de la polymérisation et la nucléation dépendaient fortement du pH, mais qu’une bonne stabilité colloïdale était néanmoins observée dans tous les cas. Ce procédé "one-pot " a ensuite été extrapolé à la synthèse de particules stabilisées par des copolymères hydrophiles de N-acryloylmorpholine (NAM) et de macromonomères d’alginate. Des nano-objets aux morphologies variées ont été obtenus. Afin de mieux appréhender la formation de ces morphologies, un système modèle employant un copolymère hydrophile de NAM et de macromonomère de polyNAM obtenu par polymérisation RAFT a été étudiépour la polymérisation en émulsion du styrène. / This work describes the synthesis of nanoparticles stabilized by polyelectrolytes from synthetic(poly((meth)acrylic acid)) or natural (alginate) source by controlled free radical polymerization (CRP),namely RAFT, in emulsion. This process is based on the use of a hydrophilic polymer prepared by RAFT (i.e. macroRAFT) which is reactivated in water for the polymerization of a hydrophobic monomer. The formation of amphiphilic block copolymers which self-assemble in situ leads to the formation of nanoparticles. Firstly, we tried to perform the whole process in water. The RAFT polymerization of acrylic acid and methacrylic acid was studied in this context. Well-defined homopolymers were obtained under a large range of conditions, and further used as macroRAFTs in emulsion polymerization of hydrophobic monomers. Stable nanoparticles composed of well-defined amphiphilic block copolymers were produced. It was shown that the control of the polymerization and the nucleation were strongly dependent on the pH. Nevertheless, a good colloidal stability wasobserved in all cases. This “one-pot” process was then extrapolated to the synthesis of particles stabilized by hydrophilic copolymers of N-acryloylmorpholine (NAM) and alginate macromonomer. Nano-objects with various morphologies were obtained. In order to better understand the formation of these morphologies, a model system using a hydrophilic copolymer of NAM and a polyNAM macromonomer obtained by RAFT polymerization was studied in styrene emulsion polymerization.