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Polymeric materials with inherent stimulus response represent an ever-growing area of research. In particular, block copolymers demonstrate exciting properties owing to their enhanced mechanical strength and microphase separation. Incorporating functionality into block copolymers proves useful in enhancing their utility. Presently, synthesis and subsequent post-polymerization modification achieved this for a range of block copolymers. In particular, neutralization of acid-containing polymers readily imparted ionic functionality and yielded microphase-separated block copolymer domains, enhancing polymer thermomechanical properties and ion transport. An ABA triblock copolymer composed of mechanically reinforcing polystyrene outer blocks and ionic central poly(1-methylimidazolium acrylate) block acted as a host for ionic liquid that caused an evolution in bulk morphology, resulting in enhanced ionic conductivity. The resulting membrane also exhibited a strong electromechanical actuation response under applied potential. Adding ionic liquid doped with a corresponding lithium salt enabled evaluation of sulfonated block copolymers as components of ternary polymer electrolytes, relevant for battery applications. Modification of a sulfonic acid-containing pentablock copolymer presented photocurable functional groups to the ionic domains which enabled their UV irradiation-induced curing. This novel route of modifying ion-containing block copolymers resulted in enhanced thermomechanical properties and enabled healing of physical defects in the film, unprecedented for ion-containing block copolymers. Covalent networks represent a relevant area of research for a wide variety of applications such as coatings, adhesives, and scaffolds. Careful design of degradable crosslinkers enables stimulus response in these networks by eliminating covalent crosslinks and affording a soluble product. Extension of poly(ethylene glycol) methacrylate-based network formation into three dimensions using microstereolithography resulted in novel acid-degradable 3D-printed parts. An additional study investigated mixtures of acrylamide-modified poly(vinyl alcohol) and poly(ethylene glycol) diacrylate as water-soluble resins for the direct formation of hydrogels from solution. Photorheology and photocalorimetry investigated the thermal and mechanical changes inherent in the curing process and evaluated the mixtures as a platform for microstereolithography. / Ph. D.

Yes / The synthesis of nucleobase-containing polymers was successfully performed by RAFT dispersion polymerization in both chloroform and 1,4-dioxane and self-assembly was induced by the polymerizations. A combination of scattering and microscopy techniques were used to characterize the morphologies. It is found that the morphologies of self-assembled nucleobase-containing polymers are solvent dependent. By varying the DP of the core-forming block, only spherical micelles with internal structures were obtained in chloroform when using only adenine-containing methacrylate or a mixture of adenine-containing methacrylate and thymine-containing methacrylate as monomers. However, higher order structures and morphology transitions were observed in 1,4-dioxane. A sphere-rod-lamella-twisted bilayer transition was observed in this study. Moreover, the kinetics of the dispersion polymerizations were studied in both solvents, suggesting a different formation mechanism in these systems. / University of Warwick, Swiss National Science Foundation, EPSRC, Birmingham Science City, Advanatfe West Midlands (AWM), European Regional Development Fund (ERDF), Science City Research Alliance, Higher Education Funding Council for England (HEFCE)

Abdominal aortic aneurysm (AAA) is a devastating disease that exhibits permanent lumen expansion typically in the infrarenal aorta. AAA is prevalent among aged population, especially in males. Despite the incidence in women is lower, studies indicate the tortuosity is more severe and aortic rupture risk is higher in women. In most patients, AAA remains asymptomatic until it ruptures leading to sudden and fatal hemorrhage. To date, there is no proven medical therapy that can prevent the expansion or rupture. Human observational studies implicate the presence of AAA is associated with both high plasma low-density lipoprotein-cholesterol (HDL-C) and low plasma high-density lipoprotein-cholesterol (HDL-C) concentrations. To examine the role of specific lipoproteins in development of AAA, angiotensin (Ang) II-induced AAA was firstly determined in apolipoprotein AI deficient (apoAI -/-) mice in both C57BL/6 and LDL receptor deficient (LDL receptor -/-) backgrounds. The deletion of apoAI led to a significant decrease of HDL-C concentrations. However, we were unable to define any exacerbation of AngII-induced AAA in either normo- or hyperlipidemic mice with apoAI deficiency. Next we compared AngII-induced AAA formation using multiple mouse strains with dietary manipulation to generate different severities of hypercholesterolemia. We demonstrated the apolipoprotein B (apoB)-containing lipoproteins promoted the development of AngII-induced AAA. Moreover, ezetimibe administration significantly reduced both apoB-containing lipoproteins and AAA formation. Together, our studies demonstrate that elevated apoB-containing lipoproteins, contribute to the development of AngII-induced AAA. To investigate the role of apoB-containing lipoproteins on established AAA, male LDL receptors -/- mice fed a Western diet were infused with AngII for 4 weeks to induced AAA. Then mice with AAA were stratified into either a group maintained on western diet or switched to a normal diet. AngII infusion was continued for an additional 8 weeks. The diet switch resulted in significantly reduced plasma cholesterol concentrations, which was attributable to the decrease of apoB-containing lipoproteins. We found a profound inhibition of aneurysm progression in diet switched mice associated with attenuated macrophage accumulation and medial thickening. Collectively, our data demonstrate that apoB-containing lipoproteins promote the progression of established AAA.

The diffusion behavior of guest molecules introduced in porous materials has been studied. Diffusion studies in such porous materials may help for elucidating the structural properties, transport mechanism and/or surface barriers of the zeolite structure. The focus of this work is on diffusion in nanoporous materials with complex pore spaces. First a short introduction in the basics of diffusion and the PFG NMR technique (Pulsed Field Gradient Nuclear Magnetic Resonance) is described. In the following two chapters the diffusion in hierarchical pore spaces or, to be more precise, zeolites with generated mesopores, which traverse the microporous bulk phase, are investigated. The hierarchical pore spaces consists in the first case of micro- and mesopores and in the second case of micro-, meso- and macropores. The diffusion behavior in these materials has been investigated revealing diffusion acceleration in the mesoporous samples, as compared to the purely microporous material. In the next chapter the diffusion behavior in glass samples with different porosity and their complementary pore space is investigated. Diffusion with full loaded pore spaces and surface diffusion, where the molecules were only able to diffuse along the pore walls, has been explored. The aim was to find out to what extent the diffusion in two complementary pore spaces is correlated. In the last chapter, the effect of an inorganic binder on the transport in zeolite pellets has been studied. First the diffusion behavior in binderless zeolite beads in comparison with the zeolite powder employed for their production has been explored. The particular interest was to find out up to which extent the diffusion patterns observed with the powder samples could again be recognized in the beads. In a second study the transport characteristics within binderless molecular sieves have been investigated, with the purpose to reveal differences in the diffusion behavior in comparison with their binder-containing counterparts.

Conducting polymers that contain metals are remarkable materials, because they have the properties of both organic backbones and metals. Depending on the position of the metal relative to the conjugated backbone, i.e. attached to or directly in the backbone, these two can couple resulting in advancement of the functionality and therefore potential applications of these types of materials. Complexes of tridentate ligands with donor atoms such as phosphorus, nitrogen, and sulfur also have a wide variety of applications. In addition, complexes of tridentate ligands have advantages of stability and control of electron density by variation of donor atoms. Therefore, conjugated polymers with tridentate ligand units will have promise for various applications and advantages in their designs. Complexes of PNP ligand with molybdenum and carbonyl ancillary ligands were synthesized and characterized. Isomerization and conversion reactions between them were investigated as well as the coordination modes. Many types of PNP ligands have been studied in the literature because the hemilabile property of the nitrogen atom promotes some catalytic reactions and gives different coordination geometries. Conducting polymers can be used as redox-active ligands and they can be used to control electron density on the metal attached to them. Synthesis and characterization of a novel polymerizable ligand 3,5-bis-EDOT-N,N-bis[2-diphenylphosphinoethyl]aniline was achieved. Related molybdenum complexes with ancillary ligands as carbonyls were also synthesized and characterized. Monomer complexes and the free ligand were electropolymerized and studied. Tris(bipyridine)ruthenium(II) chloride and analogous complexes have been studied extensively in the literature due to their luminescent and photochemical properties, and excited state lifetimes. Conducting polymers with similar ruthenium groups have been investigated for various applications. Synthesis of four ruthenium complexes with the polymerizable ligand 2,6-Bis[4-[2-(3,4-diethylenedioxy)thiophene]pyrazol-1-yl]pyridine and four different bidentate ligands were reproduced; electropolymerizations of the complexes were achieved; electrochemical, UV-Vis and luminescence studies were performed and discussed. Various complexes of copper, silver, platinum, and palladium with nitrogen and phosphorus donors have been reported for their luminescence behavior as well as their interesting structures. Model complexes of these metals with N,N-bis[2-(diphenylphosphino)ethyl]phenyl-amine (a PNP ligand) have been synthesized and characterized. Absorption and luminescence behaviors as well as the coordination modes were investigated. / text

Les subtélomères forment la transition entre les séquences spécifiques des chromosomes et les répétitions télomériques terminales. Ils semblent capables d’influencer les fonctions télomériques mais les connaissances sur les mécanismes mis en jeu sont encore limitées. Les subtélomères sont pourtant associés à de nombreuses pathologies comme la myopathie facio-scapulo-humérale (FSHD), une dystrophie musculaire secondaire à la contraction de répétitions macrosatellites D4Z4 dans la région subtélomérique 4q35. Afin d’étudier les propriétés de la séquence subtélomérique D4Z4, nous avons créé des constructions reproduisant l’organisation génomique au locus 4q35. Nous avons montré que D4Z4 est capable d’adresser un télomère à la périphérie du noyau. Cette activité est couplée à une activité insulatrice au niveau d’une séquence proximale de 80 pb et est dépendante de CTCF et des Lamines A. De plus, la relocalisation périphérique d’un télomère par D4Z4 s’accompagne d’une réplication plus tardive de celui-ci. Par ailleurs, la recherche de séquences capables de s’opposer à l’effet de position télomérique (TPE) a identifié un élément de 30 pb contenant un site CTCF dans la séquence insulatrice proximale de D4Z4. De même,   l’introduction d’un signal de poly-adénylation entre un gène rapporteur et les répétitions télomériques interfère avec le TPE et est accompagnée d’une diminution d’un transcrit hybride contenant le gène rapporteur et des répétitions télomériques, suggérant un rôle des transcrits télomériques TERRAs dans la régulation du TPE. En conclusion, ce travail a permis de caractériser l’implication de séquences subtélomériques, et notamment D4Z4, dans la régulation des télomères, leur compartimentalisation nucléaire, la réplication ou l’effet de position télomérique. De plus, il apporte un éclairage nouveau sur la physiopathologie de la FSHD et ouvre des perspectives dans la compréhension d’autres pathologies liées aux subtélomères. / Subtelomeres form the transition between chromosome specific sequences and terminal telomeric repeats. They might influence telomeric functions but underlying mechanisms are still unclear. Nevertheless, subtelomeres are associated with a number of human pathologies such as facioscapulohumeral muscular dystrophy (FSHD), an autosomal dominant disease secondary to the contraction of an array of D4Z4 macrosatellite repeats in the subtelomeric region 4q35. In order to study the biological function of the D4Z4 sequence, we created contructs that mimic the genomic organization of the 4q35 locus. We showed that D4Z4 is able to localize a telomere at the nuclear periphery. This perinuclear activity was dependant on interactions with CTCF and A type lamins and lied within a 80 bp proximal sequence that harbors an insulator activity. Moreover, the peripheral positionning of a telomere by D4Z4 is accompanied by a late replication timing of the telomere. We also searched for sequences able to counteract telomeric position effect (TPE) and identified a 30 bp element containing a CTCF binding site in the proximal region of D4Z4. In another construct, the introduction of a poly-adenylation signal between a reporter gene and telomeric repeats counteracted TPE. This effect is accompanied by the production of a hybrid transcript encompassing the reporter gene and telomeric repeats, suggesting a role for the TERRAs telomeric transcripts in TPE regulation. This work contibuted to characterize the role of subtelomeric sequences, especially the D4Z4 macrosatellite, in telomere regulation, their nuclear compartimentalization, their replication or the telomeric position effect. We will discuss the implications in the understanding of the pathophysiology of FSHD and other subtelomeric diseases.

Heme-based gas sensing proteins belong to a group of proteins that are present in signalling pathways of bacteria. A precise regulation of physiological functions, such as intercellular communication or biofilm production, is essential for the survival of these bacteria and their adaptation to the changing surrounding conditions. Heme-based gas sensors are able to detect the concentration of gas molecules in the local environment via their sensory domain (which contains a heme molecule as the intrinsic detection site) and transmit the signal to the functional domain helping to regulate the adaptation of many processes. These, often pathogenic, processes contribute to extended resistance of bacteria against antibiotics. Heme-based sensors are thus potentially a new therapeutic object of interest in antimicrobial treatment. In order to provide this type of treatment, it is crucial to understand the exact mechanism of intramolecular signal transduction facilitated by heme-based sensors. One of the approaches to unravel these mechanisms is further study of model sensory proteins. This thesis focuses on the analysis of a signal transduction performed by two model globin-coupled heme-based oxygen sensors.