Recently, a particular interest has been devoted to “smart”/stimuli-responsive amphiphilic polymeric materials. Strictly speaking, such structures do not present an amphiphilic character but can be transformed as such by external stimuli within their close environment, e.g., pH, temperature, light, ionic strength, ... and are then able to produce reversible self-assemblies greatly attractive in the biomedical field as drug delivery systems. The originality of this thesis relies upon the synthesis of “intelligent” hydrophilic triblock copolymers containing acrylamide and acrylate-based monomers presenting both thermo- and pH-responsiveness. The applied synthetic strategy aimed at performing the controlled copolymerization reactions entirely in aqueous conditions and in a “one-pot process” via Atom Transfer Radical Polymerization (ATRP). This synthetic approach represents a real challenge knowing that ATRP of (meth)acrylamide comonomers is difficult to control in aqueous medium. However, by the help of kinetic studies and related theoretical modeling, a fine control over the copolymerization process has been made available allowing the synthesis of polyacrylamide-based triblock copolymers with different charge states. Ultimately, all series of triblock copolymers have been investigated for forming polyelectrolyte complexes potentially useful as drug delivery (nano)systems. The first part of the thesis aims at reporting the control and the understanding of the aqueous ATRP of N-isopropylacrylamide (NIPAAm) initiated by a model low molecular weight initiator. The NIPAAm polymerization has been kinetically studied varying different parameters. Correlated with a theoretical modeling, the reactions involved in the ATRP process have been identified highlighting the importance of molecular diffusion limitations. This step was crucial in view to extrapolate to the synthesis of poly(N-isopropylacrylamide)-based copolymers. The second part focuses on the controlled synthesis of poly(ethylene oxide)-b-poly(N- isopropylacrylamide) diblock copolymers using the macroinitiator method. Different conditions such as solvent mixture, nature of the catalyst and of macroinitiator, i.e., poly(ethylene oxide), have been studied ultimately yielding well-tailored polyacrylamide-based triblock copolymers based on NIPAAm, N,N-dimethylaminoethyl acrylate and 2-acrylamido-2-methyl-1-propane sodium sulfonate comonomers The “smart” character of the resulting triblock copolymers has been investigated affording in specific conditions micellar self-assemblies. Last but not least, polyelectrolyte complexes have been prepared by coulombic interactions between the resulting triblock copolymers, e.g., poly(ethylene oxide)-b-poly(N- isopropylacrylamide)-b-poly(N,N-dimethylaminoethyl acrylate) and poly(ethylene oxide)-b- poly(N-isopropylacrylamide)-b-poly(2-acrylamido-2-methyl-1-propane sodium sulfonate) whose the thermo-responsiveness could be highlighted. The so-formed polyelectrolyte complex nanoparticles constitute promising nanovectors of the third generation able to kinetically tune the drug release in function of local temperature variation.

Reported in this thesis are the studies of micellar aggregates of four triblock copolymers and the unimolecular micelles of a triblock copolymer. The micelles were prepared from BCF and ACF copolymers. Here A, B, C, and F denote poly(acrylic acid), poly(tert-butyl acrylate), poly(2-cinnamoyloxylethyl methacrylate), and the liquid crystalline poly(perfluorooctylethyl methacrylate) block, respectively. At room temperature (21 oC) in solvents that were selective for the A or B blocks, three of the four copolymers formed exclusively cylindrical micelles regardless of their block ratios. Cylindrical micelles were formed because their geometries best accommodated the mesogen-ordering requirement of the core-forming F block, as supported by the results from wide angle X-ray scattering and differential scanning calorimetric studies. Mesogen-driven cylinder formation was further supported by the observation of ridges formed by collapsed coronal chains on the surfaces of dried cylinders. We also observed a morphological transformation from other micellar morphologies to cylindrical micelles at 70 oC, which is near the isotropic-to-smectic A phase transition temperature for the F blocks. This inter-conversion between the vesicular and cylindrical micelles of an ACF sample could be reversed repeatly by temperature cycling. These results provided additional evidence for the mesogen-driven micellization hypothesis. Unimolecular micelles were prepared from CDC triblock copolymers, where D and C denote poly(dimethylaminoethyl methacrylate) and poly(2-cinnamoyloxylethyl methacrylate), respectively. In selective solvents for the D block at high dilutions, the D chain formed a loop, and the terminal C blocks of the isolated unimer chain associated together as a globule, thus closing the loop and rendering a cyclic structure. Alternatively, the terminal C blocks formed individual globules, thus yielding a pompom-coil-pompom structure. To lock in these structures, the globules were photo-crosslinked. The D block chain was subsequently enlarged for AFM observation through a quaternization step, which increased the chain’s diameter and introduced cations to the chain. The semi-flexible thickened polymer chains and the globules were observed by AFM, confirming unambiguously the hypothesized architectures of the unimolecular micelles. The AFM images also allowed the quantification of the macrocyclic structures, and a correlation between the direct AFM results and determined from a traditional size exclusion chromatography technique. / Thesis (Ph.D, Chemistry) -- Queen's University, 2011-09-26 12:08:28.263

Crosslinkable and pH-sensitive amphiphilic block copolymers are promising candidates to establish pH-stable and permeable vesicles for synthetic biology. Here, we report the fabrication of crosslinked and pH-stable polymersomes as swellable vesicles for the pH-dependent loading and release of small dye molecules. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

This work presents the synthesis and the self-assembly of symmetrical amphiphilic ABA and BAB triblock copolymers in dilute, semi-concentrated and highly concentrated aqueous solution. A series of new bifunctional bistrithiocarbonates as RAFT agents was used to synthesise these triblock copolymers, which are characterised by a long hydrophilic middle block and relatively small, but strongly hydrophobic end blocks. As hydrophilic A blocks, poly(N-isopropylacrylamide) (PNIPAM) and poly(methoxy diethylene glycol acrylate) (PMDEGA) were employed, while as hydrophobic B blocks, poly(4-tert-butyl styrene), polystyrene, poly(3,5-dibromo benzyl acrylate), poly(2-ethylhexyl acrylate), and poly(octadecyl acrylate) were explored as building blocks with different hydrophobicities and glass transition temperatures. The five bifunctional trithiocarbonates synthesised belong to two classes: the first are RAFT agents, which position the active group of the growing polymer chain at the outer ends of the polymer (Z-C(=S)-S-R-S-C(=S)-Z, type I). The second class places the active groups in the middle of the growing polymer chain (R-S-C(=S)-Z-C(=S)-S-R, type II). These RAFT agents enable the straightforward synthesis of amphiphilic triblock copolymers in only two steps, allowing to vary the nature of the hydrophobic blocks as well as the length of the hydrophobic and hydrophilic blocks broadly with good molar mass control and narrow polydispersities. Specific side reactions were observed among some RAFT agents including the elimination of ethylenetrithiocarbonate in the early stage of the polymerisation of styrene mediated by certain agents of the type II, while the use of the RAFT agents of type I resulted in retardation of the chain extension of PNIPAM with styrene. These results underline the need of a careful choice of RAFT agents for a given task. The various copolymers self-assemble in dilute and semi-concentrated aqueous solution into small flower-like micelles. No indication for the formation of micellar clusters was found, while only at high concentration, physical hydrogels are formed. The reversible thermoresponsive behaviour of the ABA and BAB type copolymer solutions in water with A made of PNIPAM was examined by turbidimetry and dynamic light scattering (DLS). The cloud point of the copolymers was nearly identical to the cloud point of the homopolymer and varied between 28-32 °C with concentrations from 0.01 to 50 wt%. This is attributed to the formation of micelles where the hydrophobic blocks are shielded from a direct contact with water, so that the hydrophobic interactions of the copolymers are nearly the same as for pure PNIPAM. Dynamic light scattering measurements showed the presence of small micelles at ambient temperature. The aggregate size dramatically increased above the cloud point, indicating a change of aggregate morphology into clusters due to the thermosensitivity of the PNIPAM block. The rheological behaviour of the amphiphilic BAB triblock copolymers demonstrated the formation of hydrogels at high concentrations, typically above 30-35 wt%. The minimum concentration to induce hydrogels decreased with the increasing glass transition temperatures and increasing length of the end blocks. The weak tendency to form hydrogels was attributed to a small share of bridged micelles only, due to the strong segregation regime occurring. In order to learn about the role of the nature of the thermoresponsive block for the aggregation, a new BAB triblock copolymer consisting of short polystyrene end blocks and PMDEGA as stimuli-responsive middle block was prepared and investigated. Contrary to PNIPAM, dilute aqueous solutions of PMDEGA and of its block copolymers showed reversible phase transition temperatures characterised by a strong dependence on the polymer composition. Moreover, the PMDEGA block copolymer allowed the formation of physical hydrogels at lower concentration, i.e. from 20 wt%. This result suggests that PMDEGA has a higher degree of water-swellability than PNIPAM. / Die Arbeit behandelt die Synthese und das Selbstorganisationsverhalten von neuen funktionellen symmetrischen "stimuli-responsiven" Triblockcopolymeren ABA und BAB in wässrigen verdünnten und höher konzentrierten Lösungen. Neue symmetrische, bifunktionelle Bistrithiocarbonate wurden als RAFT-Agentien benutzt, um Triblockcopolymere mit langen hydrophilen (A) Innen- und kurzen hydrophoben (B) Außenblöcken zu synthetisieren. Als hydrophile A Blöcke wurden Poly(N-isopropylacrylamid) PNIPAM und Poly(methoxy diethylene glykol acrylat) PMDEGA benutzt, während als hydrophobe Blöcke B Poly(4-tert-butyl styrol), Polystyrol, Poly(3,5-dibromo benzyl acrylat), Poly(2-ethylhexyl acrylat), und Poly(octadecyl acrylat) als Bausteine mit unterschiedlicher Glasübergangstemperatur untersucht wurden. Die Selbstorganisation von ABA und BAB Copolymeren in Wasser mit A Blöcken aus PNIPAM wurde anhand von Trübungsphotometrie, dynamischer Lichtstreuung (DLS) und Rheologie untersucht. Die amphiphilen Blockcopolymere sind direkt wasserlöslich. Bei Konzentrationen von 0.01 bis 50 wt% zeigen Trübungsmessungen bei den Blockcopolymeren wie bei den Homopolymeren eine Übergangstemperatur bei 28-32 °C. Zurückzuführen ist dies auf die Bildung von Mizellen, bei der die hydrophoben Blöcke von einem direkten Kontakt mit Wasser abgeschirmt werden. DLS zeigt kleine Mizellen bei niedrigen Temperaturen und Aggregate mit großem hydrodynamischem Durchmesser bei Temperaturen oberhalb der Übergangstemperatur. Die rheologische Untersuchung von BAB Polymeren zeigt die Bildung von Hydrogelen bei höheren Konzentrationen (über 30-35 wt%). Die minimal benötigte Konzentration, bei der die von Hydrogelen auftreten, nimmt mit wachsender Glasübergangstemperatur ab, und nimmt mit der Länge der hydrophoben Blöcke B zu. Im Unterschied zu PNIPAM zeigen wässrige Lösungen von PMDEGA und seinen Blockcopolymeren reversible Übergangstemperaturen abhängig von der chemischen Struktur. Außerdem bilden PMDEGA Blockcopolymere Hydrogele bei niedriger Konzentration (ab 20 wt%). Dieses Ergebnis deutet darauf hin, dass PMDEGA stärker Wasser bindet als PNIPAM.

The goal of this research is to cover a broad set of scientific investigations of elastomeric materials based on polydimethylsiloxane (PDMS) and poly((3,3,3-trifluoroethoxymethyl)methyloxetane) diol. The scope of study covers five areas, well correlated with each other. The first study investigates the near surface morphology of condensation cured PDMS as a function of increasing the amount of siliceous phase. The appearance, disappearance and reappearance of untreated fumed silica nanoparticles at the PDMS near surface and their correlation with the volume fraction of siliceous phase have been studied. This research with PDMS nanocomposites has led to the development of an alternative route for improving mechanical strength of PDMS elastomers, conventionally known to have weak mechanical properties. The second study involves synthesis of a triblock copolymer comprising of four mutually immiscible phases, namely, soft segments comprising of fluorous and silicone domains, a diisocyanate hard segment and a glassy siliceous phase. Structure-property relationship has been established with an investigation of the interesting surface and bulk morphology. The highly improved mechanical strength of these soft materials is noteworthy. The dominance of silicone soft block at the triblock near surface has led to the third study which investigates their potential non-adhesive or abhesive characteristic in both a laboratory scale and in a marine environment. The peak removal stress and the removal energy associated with the detachment of a rigid object from the surface of these triblock copolymers have been measured. Results obtained from laboratory scale experiments have been verified by static immersion tests performed in the marine environment, involving the removal of adhered soft and hard fouling organisms. Gaining insights on the characteristics of an easy release surface, namely low surface energy and a low near surface modulus, a new way for controlling the near surface composition for elastomeric coatings have been developed. This technique involves an elastomer end-capped with a siliceous crosslinking agent and a tough, linear polyurethane. The basic concept behind the hybrid compositions is to develop a coating suitable for foul release applications, having a low energy surface, low surface modulus but good bulk mechanical strength. Henceforth, the fourth study deals with synthesis and characterization of the hybrid polymers over a wide range of composition and investigates their foul release characteristic in laborartory scale experiments. In our final study, attempts have been made in generating a silicone coating with antimicrobial property. A quaternary alkylammonium in different weight percents have been incorporated into a conventional, condensation cured polydimethylsiloxane (PDMS) elastomer. Antimicrobial assay has been performed on these modified silicone coatings to assess their biocidal activity against strains of Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa. Surface accessibility of quaternary charges has been quantified by measuring the streaming potential of a modified coating. An effort has been made in improving the mechanical strength of the weak PDMS elastomers by adding treated fumed silica nanoparticles as reinforcements. The effect of adding fillers on the mechanical property (tensile), surface concentration of quaternary charge and on the biocidal activity of a representative sample has been investigated.

Sixteen millions of people are diabetics in the United States. Finding an oral way to deliver the insulin they need would improve the quality of their life. For this purpose biodegradable and biocompatible nanovesicles encapsulating some insulin have been synthesized. Those nanovesicles are made by self-assembly of a triblock copolymer poly(ethylene glycol)-bpoly( lactic acid)-b-poly(glutamic acid) (PEG-b-PLA-b-PGlu). The triblock copolymer has been prepared in several steps by multi-step anionic ringopening polymerization. The first step consisted in the preparation of the diblock copolymer PEG-b-PLA. This diblock copolymer was synthesized by ring opening of racemic lactide, using a zinc alkoxide as an initiator. The second step was the synthesis of the poly(glutamic acid). The polybenzyl(glutamic acid) was obtained by ring opening polymerization of the N-Carboxyanhydride of the corresponding amino acid. Finally, the benzyl group was deprotected via protonolysis, to generate the homopolymer. This triblock was successfully obtained by coupling a diblock copolymer PEG-bxv PLA and a homopolymer poly(glutamic acid). In the presence of an aqueous solution of insulin where the pH is between 7 and 9, the triblock copolymer self-assembles in nanovesicles containing a part of the free insulin. In the intestine, the vesicles are highly solvated due to the deprotonnated poly(glutamic acid) hair which are expected to be located on the outside. Moreover, to resist from the gastric acidity, the nanovesicles are protected with gastro resistant polymer, Eudragit, which stay solid at acidic pH but get dissolved in the intestine (where the pH is slightly basic), releasing the vesicles. All the polymers have been characterized using 1H NMR and GPC. The percentage of encapsulation of insulin has been measured by HPLC some in-vivo experiments have been done on Sprague-Dawley rats.

Styrenic block copolymer thermoplastic elastomers are one of the most widely used thermoplastic elastomers (TPEs) today. The focus of this research is to fundamentally understand the structure-processs-property relationships in these materials. Deformation behavior of the block copolymers with cylindrical and lamellar morphologies has been investigated in detail using unique techniques like deformation calorimetry, transmission electron microscopy (TEM), combined in-situ small angle x-ray and wide angle x-ray scattering (SAXS/WAXS). The research involves the study of structural changes that occur at different length scales along with the energetics involved upon deformation. The structural changes in the morphology of these systems on deformation have been investigated using combined SAXS/WAXS setup. Small angle x-ray scattering probed the changes at the nano-scale of polystyrene (PS) cylinders, while wide angle x-ray scattering probed the changes at molecular length scales of the amorphous/crystalline domains of the elastomeric mid-block in these systems. TEM analysis of the crosslinked elastomers (by UV curing) further confirms the interpretation of structural details as obtained from SAXS upon deformation. New structural features at both these length scales have been observed and incorporated into the overall deformation mechanisms of the material. Characteristic structural parameters have been correlated to differences in their mechanical response in the commercially relevant cylindrical block copolymers. Effect of various process conditions and thermal treatments has been investigated. The process conditions affect the structure at both micro-scopic (grain size) and nano-scopic (domain size) length scales. A correlation has been obtained between a mechanical property (elastic modulus) and an easily measurable structural parameter (d-spacing). Effect of various phase transitions such as order-to-order transition has been studied. Selective solvents can preferentially swell one phase of the block copolymer relative to other and thus bring a change in morphology. Such kinetically trapped structures when annealed at higher temperature try to achieve their thermodynamic equilibrium state. Such changes in morphology significantly affect their tensile and hysteretic response. In another work it has been shown that by carefully compounding these styrenic block copolymers having different morphologies, it is possible to completely disrupt the local scale order and remove the grain boundaries present in these materials. Finally, a new test technique has been developed, by modifying an existing Charpy device to test polymeric films at a high strain rate. A custom designed load-cell is used for force measurements which imposes harmonic oscillations on a monotonic loading signal. The data obtained from this device can be used to analyze visco-elastic response of polymeric films at frequencies much higher than the conventional dynamic mechanical analyzer (DMA).

Microemulsions have important applications in various industries, including enhanced oil recovery, reactions, separations, drug delivery, cosmetics and foods. We investigated two different kinds of water-in-oil microemulsion systems, AOT (bis(2-ethylhexyl) sulfosuccinate) microemulsions with various counterions and perfluorocarbon-based microemulsion gels with triblock copolymers. In the AOT systems, we investigated the viscosity and interdroplet interactions in Ca(AOT)2, Mg(AOT)2 and KAOT microemulsions, and compared our results with the commonly-studied NaAOT/water/decane system. We attribute the differences in behavior to different hydration characteristics of the counterions, and we believe that the results are consistent with a previously proposed charge fluctuation model. Perfluorocarbons (PFCs) are of interest in a variety of biomedical applications as oxygen carriers. We have used triblock copolymer Pluronic® F127 to modify the rheology of PFC-based microemulsions, we have been able to form thermoreversible PFOB (perfluorooctyl bromide)-based gels, and have investigated the phase stability, rheology, microstructure, interactions, and gelation mechanism using scattering, rheometry, and microscopy. Finally, we attempted to use these data to understand the relationship between rheology and structure in soft attractive colloids.

For the first time, triblock copolymers of novel styrenic-based macromolecules were investigated in detail and examined for structure-morphology-performance relationships. We were able to design novel imidazolium- and phosphonium-containing styrenic macromolecules using controlled radical polymerization and conventional free radical polymerization strategies, for a variety of potential applications including electromechanical devices, ionic liquids, adhesives, and lithium-ion batteries. Block copolymers have a unique architecture providing physical crosslinking to behave as thermoplastic elastomers. We preferred ABA triblock copolymers as compared to random and diblock copolymers for improved mechanical performance. ABA triblock copolymers synthesized using nitroxide-mediated polymerization (NMP) of polystyrene external blocks and a charged imidazolium-containing central block, exhibited sufficient modulus and ionic conductivity for electromechanical transducers. We successfully reported the actuation behavior of triblock copolymers in the presence of added ionic liquid for the first time. We proposed that diluting the ion concentration of the ion-rich phase with neutral polymer comonomers that reduces Tg, increases ion dissociation, and potentially maximizes ionic conductivity. Tendency of ethylene-oxide units to coordinate cations, forming stable crown ether-like, multi-nuclear coordination complexes, promotes solvation and dissociation of ionic aggregates. In situ Fourier transform infrared spectroscopy (FTIR) was used to monitor the thermal polymerization in various acrylate and methacrylate monomers. It was found that acrylates have lower activation energy than methacrylates. The copolymerizations of poly(ethylene glycol)methyl ether acrylate (EG9MEA) and imidazole-containing monomer (VBIm) resulted in controlled polymerization kinetics with narrow molecular weight distributions. The control behavior of the copolymerizations is likely attributed to the observed decrease in calculated apparent rate constants for the copolymerizations with addition of VBIm as comonomer. Reversible addition fragmentation transfer (RAFT) successfully synthesized well-defined A-BC-A triblock copolymers containing a synergy of pendant ether and imidazolium sites. We demonstrated that electromechanical transducers derived from these triblock copolymer membranes with added ionic liquid showed superior actuation performance compared to a benchmark Nafion® membrane, suggesting potential for ionic polymer device applications. This was attributed to optimum modulus, improved ionic conductivity, and microphase-separated morphology of triblock copolymers. Conventional free radical polymerization and anion metathesis of 4-(diphenylphosphino)styrene (DPPS) successfully generated high molecular weight triaryl phosphine-containing copolymers. These macromolecules have no -CH2 group at the benzylic position increasing the thermal stability of the DPPS-containing polymers. Counterion exchange to fluorinated, bulkier anions broadened the library of polyelectrolytes, led to improved thermal stabilities, lower glass transition temperatures, and tunable wetting behavior. We also reported the synthesis of salt-responsive copolymers using conventional free radical polymerization. Adhesive performance measurements such as peel tests and probe tack enforced the application of these polymers as pressure sensitive adhesives. We also demonstrated the synthesis and subsequent neutralization of novel, well-defined A-BC-A triblock copolymers containing a soft central 'BC' block consisting of Sty-Tf2N and DEGMEMA with polystyrene external blocks. Sty-Tf2N monomer enables an important delocalization of the negative charge. Li+ has weak interactions with this anionic structure, consequently enabling a high dissociation level. Li+ ions are associated to the polymer chain to produce high transport numbers. Furthermore, incorporating DEGMEMA lowers the Tg of the charged block copolymers, thereby increasing the segmental mobility and thus ionic conductivity. Finally, the structure-property-morphology study of these triblock copolymers will be helpful for their use in potential applications such as ion-containing membranes, lithium-ion batteries. / Ph. D.

Crosslinkable and pH-sensitive amphiphilic block copolymers are promising candidates to establish pH-stable and permeable vesicles for synthetic biology. Here, we report the fabrication of crosslinked and pH-stable polymersomes as swellable vesicles for the pH-dependent loading and release of small dye molecules. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.