L'objectif de ces travaux était de mettre au point une nouvelle voie de modification de la silice comme renfort d'élastomères silicones. La polymérisation par ouverture de cyclosiloxanes anionique (POCA) amorcée directement à partir de la silice dispersée en phase aqueuse a été réalisée. Les caractéristiques des silices utilisées dans cette étude ainsi que leur comportement en dispersion aqueuse ont tout d'abord été étudiés. La silice affiche des groupements silanolates à la surface de la silice pour des pH supérieurs au point de charge nulle. A pH 7, ces groupements silanolates en surface sont capables d'amorcer une polymérisation des cyclosiloxanes, et pas en suspension aqueuse. L'influence du contre-ion et de sa concentration sur le greffage obtenu s'est avérée primordiale, en complément des propriétés adsorbantes de la silice via les liaisons siloxanes. Les silices obtenues par ce nouveau procédé ont fait l'objet d'analyses poussées par thermogravimétrie, fragmentation-CPG, 29Si RMN simple impulsion et pyrolyse CPG-SM dans le but de décrire précisément la conformation du greffage. Le procédé a été transféré à plus grande échelle pour permettre la production d'importantes quantités de silice qui ont ensuite été incorporées dans une matrice silicone. Des limites de densités de greffage au-delà et en deçà desquelles la silice est mal dispersée dans le matériau ont été mises en évidence par traitement d'image. Les propriétés des élastomères ont été évaluées à partir de tests de dureté, de traction uniaxiale, de traction cyclique et de résistance à la déchirure dans le but d'étudier l'influence du greffage (conformation et groupements vinylés) sur le renforcement. / This work deals with a new way of modifying silica surface in a view to reinforce silicone elastomers. The surface-initiated ring-opening-polymerization (Si-ROP) of cyclosiloxanes was performed directly from the surface of silica dispersed in water. The characteristics of silica used in this study and their behavior in aqueous dispersion were first studied. For pH higher than the Point of Zero Charge, silica presents silanolate groups at its surface that are able to initiate the ROP of cyclosiloxanes from the surface, and not in aqueous suspension. The influence of the counter-cation and its concentration proved to be essential, in addition to silica's adsorbing properties. Modified silicas obtained by this new process were deeply analyzed by thermogravimetric analyses (TGA), fragmentation-GC, simple impulsion 29Si RMN and pyrolysis GC-MS in order to describe precisely the grafting conformation. The polymerization process was then scaled up to produce higher quantities of modified silica, which were incorporated in a model silicone formulation. Highest and lowest grafting densities tended to poor silica dispersions, as shown by image treatment. Hardness tests, uniaxial tensile and cyclic tests and tear resistance tests were performed in order to evaluate the influence of the grafting (conformation and vinylated groups) on silicone elastomers properties.

Dans un premier chapitre, nous avons présenté un historique succinct de la chimiothérapie antivirale et l'utilisation d'analogues nucléos(t)idiques. Nous nous sommes focalisés en particulier sur les nucléosides phosphonates acycliques (ANP) en tant qu'antiviraux potentiels. Dans un second chapitre, nous avons décrit la synthèse de β-céto, β-hydroxylamino et β-O-(benzyl)hydroxylamino ANP dérivés de l'adénine et de la cytosine. Les isomèrs (R) et (S)-β-hydroxy-ANP ont été préparés par dédoublement du racémique correspondant avec le (S)-MPA et l'attribution des configurations absolues a été effectuée par RMN et calculs de modélisation moléculaire. Nous avons aussi développé une méthodologie de synthèse de β-azido-ANP, ces derniers étant utilisés pour la préparation de β-amino-ANP par hydrogénation catalytique. Dans un troisième chapitre, nous avons présenté la synthèse des 2H-azirine et cis-aziridne-ANP et examiné lʹ ouverture de cycle comme voie d'accès à des ANP α,β-fonctionnalisés. Les propriétés biologiques de ces nouveaux ANP ont été évaluées en culture cellulaire sur un certain nombre de virus à ADN et ARN. / In the first chapter, we presented a brief history of antiviral chemotherapy and use of nucleos(t)ide analogues, especially acyclic nucleoside phosphonates as potential antiviral agents. In the chapter-II we have successfully synthesized ¦Â-keto, ¦Â-hydroxylamino and ¦Â-O-(benzyl)hydroxylamino ANPs of adenine and cytosine derivatives. Then (R) and (S)-¦Â-hydroxy-ANPs were prepared via chiral resolution of racemic ¦Â-hydroxy-ANPs with (S)-MPA and assignment of absolute configuration was achieved using NMR and molecular modeling studies. We also developed a methodology for the synthesis of ¦Â-azido-ANPs and those were used for the preparation of ¦Â-amino-ANPs by catalytic hydrogenation. In third chapter, we synthesized 2H-azirine and cis-aziridine-ANPs and explored their ring opening to functionalized ¦Á,¦Â-ANPs. The novel ANPs obtained during this study were evaluated for their inhibitory effect on a number of DNA and RNA viruses in cell culture experiments.

D’après l’Organisation Mondiale de la Santé (OMS), les maladies cardiovasculaires (CVDs) sont la cause majeure de morbidité et de mortalité dans le monde. Dans un contexte où les thérapies non chirurgicales impliquent une administration de molécules actives à hautes doses, limiter les effets secondaires et augmenter l’efficacité thérapeutique est un enjeu majeur. Une possible réponse à cette problématique est l’utilisation de nanoparticules polymères encapsulant des molécules actives. Pour des applications de délivrance de principe actif et/ou de génie tissulaire, les polymères utilisés doivent suivre certains critères : (i) la biodégradabilité ; (ii) la biocompatibilité ; (iii) l’uniformité des chaînes polymères et (iv) une fonctionnalisation aisée par les molécules d’intérêt. Dans ce contexte, des copolymères dégradables obtenus par polymérisation radicalaire par ouverture de cycle (rROP) entre les acétals de cétène cyclique (CKAs) et des monomères vinyliques semblent satisfaire à ces critères. En effet, les CKAs sont des monomères cycliques qui s’ouvrent par voie radicalaire et permettent la formation de fonctions esters dans le squelette polymère au cours de la polymérisation. Hormis les CKAs bien connus (e.g., 2-methylene-1,3-dioxepane (MDO), et 2-methylene-4-phenyl-1,3-dioxolane (MPDL)), un besoin de nouveaux CKAs plus hydrophiles et/ou avec de nouvelles fonctionnalités est récemment apparu. Par conséquent la synthèse de nouveaux CKAs a été étudiée.Par ailleurs, les calculs par la théorie de la fonctionnelle de la densité (DFT) ont démontré que la copolymérisation radicalaire du MDO avec des dérivés d’éther de vinyle (VE) était quasi idéale, ce qui fut par la suite confirmé expérimentalement. Ainsi, ce système a permis l’obtention via un mécanisme radicalaire de copolymères similaires à des polyesters, en particulier à la polycaprolactone (PCL), hautement fonctionnels via l’utilisation de divers VE. La dégradation hydrolytique des P(MDO-co-VE) ainsi obtenus a été étudiée en conditions accélérées et physiologiques. Les copolymères ont montré une vitesse de dégradation dépendant du taux de MDO et de la nature du VE. L’hydrolyse en conditions physiologiques des P(MDO-co-VE) a donné des taux de dégradation comparables à ceux obtenus pour l’acide polylactique (PLA) et la PCL, tous deux approuvés par l’agence américaine des produits alimentaires et médicamenteux (FDA). La dégradation enzymatique assistée par les lipases Candida antartica a également été étudiée, donnant une dégradation quasi complète des copolymères en 48 h. En plus d’être biodégradables, l’avantage des P(MDO-co-VE) est que les fonctions portées par les VE ont permis une fonctionnalisation aisée des copolymères via le greffage de petites molécules ou des macromolécules telles que des chaînes de poly(éthylène glycol) (PEG) ; soit après polymérisation (approche “grafting to”) soit avant polymérisation (approche “grafting through”). Les propriétés physico-chimiques ont pu être finement ajustées, permettant ainsi la formulation de nanoparticules stables convenant à des applications de délivrance de principes actifs. / According to the World Health Organization (WHO), cardiovascular diseases (CVDs) are the major cause of morbidity and mortality in the world. In a context where non-surgical therapy involves active molecules administration at high doses, circumventing possible toxic side effects and increasing the therapeutic effect is a major challenge. Thus, the use of drug-loaded polymeric nanoparticles may represent a potential solution to this problem. For drug delivery and/or tissue engineering applications, polymers should follow some criteria: (i) biodegradability; (ii) biocompatibility; (iii) uniformity of the polymer chain and (iv) possibility of functionalization with molecules of interest. As such, degradable copolymers were obtained by radical ring-opening copolymerization (rROP) between cyclic ketene acetals (CKAs) and vinylic monomers and fulfilled all those criteria. Indeed, CKAs are cyclic monomers which open through a radical mechanism and give degradable ester functions in the polymer backbone upon polymerization. Besides well-known CKAs (e.g., 2-methylene-1,3-dioxepane (MDO), and 2-methylene-4-phenyl-1,3-dioxolane (MPDL)), a crucial need for new CKAs that would be more hydrophilic and/or with new functionalities has recently emerged. Therefore, synthesis of new CKAs was investigated.In addition, the rROP of MDO and vinyl ether (VE) derivatives was predicted to be quasi-ideal by Density Functional Theory (DFT) calculations and subsequently confirmed experimentally. Thus, this system gave the opportunity to obtain polyester-like copolymers, especially polycaprolactone-like polymers, highly functional from the use of functional VE derivatives. Hydrolytic degradation of the resulting P(MDO-co-VE) was investigated under accelerated and physiological conditions. Copolymers showed tunable degradation rate as a function of the MDO content and of the nature of the VE. Hydrolysis in physiological conditions of P(MDO-co-VE) copolymers led to a degradation rate comprised between those obtained for polylactide (PLA) and PCL, both approved by the Food and Drug Administration (FDA). Enzymatic degradation by lipases Candida antartica was also studied, leading to nearly complete degradation in 48 h. In addition to be hydrolytically and enzymatically degradable, a strong advantage of P(MDO-co-VE) copolymers rely in their easiness of functionalization via the use of various VE moieties, leading to efficient grafting by small molecules or macromolecules such as poly(ethylene glycol) (PEG) chains; either after polymerization (“grafting to” approach) or before polymerization (“grafting through” approach). Physicochemical properties were finely tuned enabling the formulation of stable nanoparticles suitable for drug delivery purpose.

The global oil refining industry with its present shift inproduct distribution towards fuels such as gasoline and dieselwill most likely hold the fort for many years to come. However,times will change and survival will very much depend onprocessing flexibility and being at the frontiers of refiningtechnology, a technology where catalysts play leading roles.Today oil refiners are faced with the challenge to producefuels that meet increasingly tight environmentalspecifications, in particular with respect to maximum sulphurcontent. At the same time, the quality of crude oil is becomingworse with higher amounts of polyaromatics, heteroatoms(sulphur and nitrogen) and heavy metals. In order to staycompetitive, it is desirable to upgrade dense streams withinthe refinery to value-added products. For example, upgradingthe fluid catalytic cracking (FCC) by-product light cycle oil(LCO) into a high quality diesel blending component is a veryattractive route and might involve a two-step catalyticprocess. In the first step the LCO is hydrotreated andheteroatoms are removed and polyaromatics are saturated, in thesecond step naphthenic rings are selectively opened to improvethe cetane number of the final product. The present research is devoted to the second catalytic stepof LCO upgrading and was carried out within the framework of aEuropean Union project entitled RESCATS. From the patent literature it is evident that iridium-basedcatalysts seem to be good candidates for ring-opening purposes.A literature survey covering ring opening of naphthenicmolecules shows the need for extending investigations toheavier model substances, more representative of the dieselfraction than model compounds such as alkylated mono C5 and C6-naphthenic rings frequently employed in academic studies. Ring-opening catalysts, mainly Pt-Ir based, were synthesisedat KTH by two different methods: the microemulsion and theincipient wetness methods. Characterization of the catalystswas performed using a number of techniques including TPR,TEM-EDX, AFM and XPS etc. Catalytic screening at atmosphericpressure using pure indan as model substance was utilized todetect ring-opening activity and the magnitude of selectivityto desired cetane-boosting products. The development of suchring-opening catalysts is the topic of Paper I. When designing a catalytic system aimed at refiningpetroleum, it is crucial to monitor the evolution of thesulphur distribution throughout the different stages of theprocess so that catalyst properties and reaction parameters canbe optimised. The final section of this thesis and Paper II arethus devoted to high-resolution sulphur distribution analysisby means of a sulphur chemiluminescence detector (SCD). Keywords:ring opening, naphthenes, cetane numberimprovement, indan, light cycle oil (LCO), Pt-Ir catalyst,catalyst characterization, aromatic sulphur compounds, GC-SCD,distribution, analysis.

No description available.

The use of synthetic materials for tissue and organ reconstruction, i. e. tissue engineering, has become a promising alternative to current surgical therapies and may overcome the shortcomings of the methods in use today. The challenge is in the design and reproducible fabrication of biocompatible and bioresorbable polymers, with suitable surface chemistry, desirable mechanical properties, and the wanted degradation profile. These material properties can be achieved in various manners, including the synthesis of homo- and copolymers along with linear and star-shaped architectures. In many applications the materials’ three-dimensional structure is almost as important as its composition and porous scaffolds with high porosity and interconnected pores that facilitate the in-growth of cells and transportation of nutrients and metabolic waste is desired. In this work linear and star-shaped polymers have been synthesized by ring-opening polymerization using a stannous-based catalyst and a spirocyclic tin initiator. A series of linear copolymers with various combinations of 1,5-dioxepane-2-one (DXO), Llactide (LLA) and ε-caprolactone (CL) have been polymerized using stannous octoate as catalyst. It is shown that the composition of the polymers can be chosen in such a manner that the materials’ mechanical and thermal properties can be predetermined. A solvent-casting and particulate leaching scaffold preparation technique has been developed and used to create three-dimensional structures with interconnected pores. The achieved physical properties of these materials’ should facilitate their use in both soft and hard tissue regeneration. Well defined star-shaped polyesters have been synthesized using a spirocyclic tin initiator where L-lactide was chosen as a model system for the investigation of the polymerization kinetics. Neither the temperature nor the solvent affects the molecular weight or the molecular weight distribution of the star-shaped polymers, which all show a molecular weight distribution below 1.19 and a molecular weight determined by the initial monomer-to-initiator concentration. / QC 20101217

Cross-linked films of ε-caprolactone (CL) and 1,5-dioxepan-2-one (DXO) having various mole fractions of monomers and different cross-link densities were prepared using 2,2’-bis-(-caprolactone-4-yl) propane (BCP) as cross-linking agent and Sn(Oct)2 as catalyst. Reaction parameters were examined to optimize the film-forming conditions. Networks obtained were elastomeric materials, easy to cast and remove from the mould. Effect of CL content and cross-link density on the final properties of the polymer network was evaluated. Thermal, mechanical and surface properties of the films were controlled by monomer feed composition and cross-link density. The films have potential to be used for tissue engineering applications as shown by preliminary cell growth studies. To avoid organometallic catalysts in the synthesis of poly(1,5-dioxepan-2-one) (PDXO), the enzyme-catalyzed ring-opening polymerization (ROP) of DXO was performed with lipase-CA (derived from Candida antarctica) as a biocatalyst. A linear relationship between number-average molecular weight (Mn) and monomer conversion was observed, which suggested that the product molecular weight can be controlled by the stoichiometry of the reactants. The monomer consumption followed a first-order rate law with respect to monomer and no chain termination occurred. Effect of reaction water content, enzyme concentration and polymerization temperature on monomer conversion and polymer properties was studied. An initial activation by heating the enzyme was sufficient to start the polymerization as monomer conversion occurred at room temperature afterwards. Terminal-functionalized polyesters and tri-block polyesters were synthesized by lipase-CA catalyzed ROP of DXO and CL in the presence of an appropriate alcohol as initiator. Alcohol bearing unsaturation introduced a double bond at the chain end of the polyester, which is a useful pathway to synthesize comb polymers. Dihydroxyl compounds were used as macro-initiators to form tri-block polyesters. The enzyme-catalyzed polymerization of lactones has been shown to be a useful method to synthesize metal-free polyesters. / QC 20101221

No description available.

This thesis describes the synthesis and application of a new series of amphiphilic graft copolymers with a hydrophobic polyolefin backbone and pendent hydrophilic poly(ethylene glycol) (PEG) grafts. These copolymers are synthesized by ruthenium benzylidene-catalyzed ring-opening metathesis polymerization (ROMP) of PEG-functionalized cyclic olefin macromonomers to afford polycyclooctene- graft -PEG (PCOE- g -PEG) copolymers with a number of tunable features, such as PEG graft density and length, crystallinity, and amphiphilicity. Macromonomers of this type were prepared first by coupling chemistry using commercially available PEG monomethyl ether derivatives and a carboxylic acid-functionalized cycloctene. In a second approach, macromonomers possessing a variety of PEG lengths were prepared by anionic polymerization of ethylene oxide initiated by cyclooctene alkoxide. This methodology affords a number of benefits compared to coupling chemistry including an expanded PEG molecular weight range, improved hydrolytic stability of the PEG-polycyclooctene linkage, and a reactive hydroxyl end-group functionality for optional attachment of biomolecules and probes. The amphiphilic nature of these graft copolymers was exploited in oil-water interfacial assembly, and the unsaturation present in the polycyclooctene backbone was utilized in covalent cross-linking reactions to afford hollow polymer capsules. In one approach, a bis -cyclooctene PEG derivative was synthesized and co-assembled with PCOE-g-PEG at the oil-water interface. Upon addition of a ruthenium benzylidene catalyst, a cross-linked polymer shell is formed through ring-opening cross-metathesis between the bis -cyclooctene cross-linker and the residual olefins in the graft copolymer. By incorporating a fluorescent-labeled cyclooctene into the graft copolymer, both oil-water interfacial segregation and effective cross-linking were confirmed using confocal laser scanning microscopy (CLSM). In a second approach, reactive functionality capable of chemical cross-linking was incorporated directly into the polymer backbone by synthesis and copolymerization of phenyl azide and acyl hydrazine-functional cyclooctene derivatives. Upon assembly, these reactive polymers were cross-linked by photolysis (in the phenyl azide case) or by addition of glutaraldehyde (in the acyl hydrazine case) to form mechanically robust polymer capsules with tunable degradability ( i.e. non-degradable or pH-dependent degradability). This process permits the preparation of both oil-in-water and water-in-oil capsules, thus enabling the encapsulation of hydrophobic or hydrophilic reagents in the capsule core. Furthermore, the assemblies can be sized from tens of microns to the 150 nm - 1 µm size range by either membrane extrusion or ultrasonication techniques. These novel capsules may be well-suited for a number of controlled release applications, where the transport of encapsulated compounds can be regulated by factors such as cross-link density, hydrolytic stability, and environmental triggers such as changes in pH.

Utilizing the diverse functionality of amino acids, a new class of amphiphilic graft copolymers has been synthesized, characterized, and explored for applications in biomaterials and nucleic acid delivery. This thesis research focused on the syntheses of oligopeptide-functionalized polyesters and polyolefins. Polyester functionalization was geared towards applications in biomaterials, tissue engineering, and drug delivery by incorporating sequences that promote cell-adhesion. These polyester- graft -oligopeptide materials were prepared by a 1,3-Huisgen cycloaddition reaction, "click" chemistry, of an azide-terminated oligopeptide (prepared by Fmoc-based solid phase peptide synthesis (SPPS)) and alkyne-containing polyester (synthesized by ring-opening polymerization). Following the syntheses of these materials, they were analyzed by nuclear magnetic resonance (NMR) and organic gel permeation chromatography (GPC). The oligopeptide-functionalized polyolefins were designed for nucleic acid complexation, and therefore the oligopeptide sequences were intended to incorporate positively-charged moieties ( e.g. , oligolysine) for DNA and short interfering RNA (siRNA) complexation. These graft copolymers, prepared by SPPS followed by ring-opening metathesis polymerization, have highly tunable structures that enable control over charge density and polymer backbone rigidity. Moreover, non-ionic hydrophilic grafts such as polyethylene glycol were integrated into these polyelectrolytes such that the charges along the polymer backbone are spaced accordingly while maintaining the hydrophilicity of the polymer. While numerous applications for such charged, "bio-tailored" materials can be envisioned, this work is geared towards positively-charged polyelectrolytes for their potential application in nucleic acid therapy, specifically the delivery of plasmid DNA and siRNA. These graft copolymers were characterized ( 1 H, 13 C NMR, organic and aqueous GPC), studied for their solution properties (static and dynamic light scattering), and investigated as polyplexes with plasmid DNA.