Polímeros heterocíclicos são macromoléculas de elevado desempenho que incluem uma grande variedade de materiais, desde simples polímeros lineares preparados a partir de monômeros do tipo heterocíclicos vinílicos, até polímeros funcionalizados e reticulados. Neste trabalho realizou-se a modificação química da poliacrilonitrila com a incorporação de grupos 2-vinil-2-oxazolina em diferentes teores (10% e 20%). Os copolímeros de acrilonitrila e 2-vinil-2-oxazolina obtidos foram caracterizados por espectroscopia na região do infravermelho e o seu comportamento térmico analisado por calorimetria diferencial de varredura e análise termogravimétrica. Os copolímeros heterocíclicos foram avaliados como inibidores de corrosão para aço-carbono em solução aquosa de HCl 10%, alcançando, em alguns casos, uma eficiência de inibição superior a 75%, com diferença estatisticamente significativa (P < 0,05, ANOVA) para a poliacrilonitrila não modificada. / Heterocyclic polymers are high-performance macromolecules that include a variety of materials, from simple linear polymers which are prepared from heterocyclic monomers like vinyl, to functionalized polymers or lattices. In this work polyacrylonitrile was chemically modified with incorporation of 2-vinyl-2-oxazoline groups at different contents (10% and 20%). Copolymers of acrylonitrile and 2-vinyl-2-oxazoline were characterized by spectroscopy in the infrared region, differential scanning calorimetry and thermogravimetric analysis. The synthesized heterocyclic copolymers were evaluated as corrosion inhibitor on carbon steel against aqueous solution of HCl 10%, and in some cases inhibition efficiencies more than 75% were determined, with statistically significant difference (P < 0.05, ANOVA) to the unmodified polyacrylonitrile.

Polímeros heterocíclicos são macromoléculas de elevado desempenho que incluem uma grande variedade de materiais, desde simples polímeros lineares preparados a partir de monômeros do tipo heterocíclicos vinílicos, até polímeros funcionalizados e reticulados. Neste trabalho realizou-se a modificação química da poliacrilonitrila com a incorporação de grupos 2-vinil-2-oxazolina em diferentes teores (10% e 20%). Os copolímeros de acrilonitrila e 2-vinil-2-oxazolina obtidos foram caracterizados por espectroscopia na região do infravermelho e o seu comportamento térmico analisado por calorimetria diferencial de varredura e análise termogravimétrica. Os copolímeros heterocíclicos foram avaliados como inibidores de corrosão para aço-carbono em solução aquosa de HCl 10%, alcançando, em alguns casos, uma eficiência de inibição superior a 75%, com diferença estatisticamente significativa (P < 0,05, ANOVA) para a poliacrilonitrila não modificada. / Heterocyclic polymers are high-performance macromolecules that include a variety of materials, from simple linear polymers which are prepared from heterocyclic monomers like vinyl, to functionalized polymers or lattices. In this work polyacrylonitrile was chemically modified with incorporation of 2-vinyl-2-oxazoline groups at different contents (10% and 20%). Copolymers of acrylonitrile and 2-vinyl-2-oxazoline were characterized by spectroscopy in the infrared region, differential scanning calorimetry and thermogravimetric analysis. The synthesized heterocyclic copolymers were evaluated as corrosion inhibitor on carbon steel against aqueous solution of HCl 10%, and in some cases inhibition efficiencies more than 75% were determined, with statistically significant difference (P < 0.05, ANOVA) to the unmodified polyacrylonitrile.

Poly (2-ethyl-2-oxazoline)-based amphiphilic diblock copolymer has the potential to form promising membrane materials for water purification due to the thermal stability and good solubility in aqueous solution and also for gas separation because of the presence of polar amide group along the polymer backbone. Moreover, their self-assembly into micelles renders them candidate materials as nanocarriers for drug delivery applications. In this study, a novel well-defined linear PEtOx-based amphiphilic diblock copolymer with a hydrophobic fluoropolymer, i.e., PVDF, have been successfully synthesized by implementing a synthesis methodology that involves the following four steps. In the first step, poly (2-ethyl-2-oxazoline) (PEtOx) was synthesized via living cationic ring-opening polymerization (LCROP) of 2-ethyl-2-oxazoline (EtOx) monomer. The “living” nature of LCROP allows the desirable termination to occur by using the proper termination agent, namely, water, to achieve the polymer with a terminal hydroxyl group, i.e., PEtOx-OH. The hydroxyl end group in PEtOx-OH was converted to PEtOx-Br using 2-bromopropionyl bromide via an esterification reaction. In the third step, the PEtOx-Br macro-CTA was subsequently reacted with potassium ethyl xanthate to insert the necessary RAFT agent via nucleophilic substitution reaction to obtain PEtOx-Xanthate. It s worth mentioning that this step is vital for the sequential addition of the second block via the RAFT polymerization reaction of fluorinated monomer, i.e., VDF, to finally obtain the well-defined amphiphilic diblock copolymer with variable controlled chain lengths. Proton Nuclear Magnetic Resonance Spectroscopy (1H-NMR) and Fourier Transform Infrared Spectroscopy (FT-IR) confirmed the structure of the macroinitiator and final copolymer, respectively. Size Exclusion Chromatography (SEC) determined the number-average molecular weight (Mn) and the polydispersity index (PDI) of the obtained copolymer. Furthermore, the polymorphism of the diblock copolymer characterized by X-Ray Diffraction (XRD) indicated that the copolymer displays the electroactive α-phase. The resultant amphiphilic diblock copolymer exhibits spherical micelles morphology, as confirmed by Dynamic Light Scattering (DLS) and Atomic Force Microscopy (AFM). Moreover, Thermogravimetric Analysis (TGA) and Differential Scanning Calorimetry (DSC) investigated the thermal decomposition behavior of the copolymer and determined the glass transition temperature (Tg ≈ 70 °C), melting temperature (Tm ≈ 160-170 °C), and crystallization temperature (Tc ≈ 135-143 °C) of the diblock copolymer, respectively.

The research presented in this thesis focuses on the synthesis of three amphiphilic block copolymer systems containing poly(ethylene oxide) (PEO) blocks. The polymer systems were developed for use in biomedical applications. The first of these is a series of poly(ethylene oxide-b-oxazoline) (PEO-b-POX) diblock copolymers for use in the progress towards novel non-viral gene transfer vectors. Poly(ethylene oxide-b-2-ethyl-2-oxazoline) (PEO-b-PEOX) and poly(ethylene oxide-b-2-methyl-2-oxazoline) (PEO-b-PMOX) were investigated. The PEOX block was hydrolyzed with acid to form linear polyethylenimine (L-PEI). The polycation L-PEI is well known for its DNA binding efficiency but the water solubility of the resulting DNA/polymer complex is limited. Addition of a PEO block is directed towards the formation of a water dispersible DNA/copolymer complex. Dynamic light scattering of the PEO-b-PEOX and PEO-b-PEI block copolymers indicated that both systems existed as single chains in aqueous solution at pH 7. PEO copolymers also play a significant role in the formation of magnetic magnetite nanoparticles, which are dispersible in water at biological pH (pH =7). There is significant interest in the design of magnetic nanoparticle fluids for biomedical applications including magnetic field-directed drug delivery, magnetic cell separations, and blood purification. For use in vivo, the magnetite nanoparticles must be coated with biocompatible materials. Such polymers render the nanoparticles dispersible in water. Harris1 et al. synthesized PEO based, polyurethane triblocks with pendant carboxylic acid groups for use in formation of stable aqueous magnetic fluids. Building from this work, two polyurethane and polyurethaneurea systems were synthesized with 1300 g/mol PEOX and 2500 g/mol and PEOX2070 g/mol poly(ethylene oxide-co-propylene oxide) tailblocks, respectively. The PEO/PPO random copolymer contained about 25 weight percent PPO, and this disrupted the capacity of the PEO to crystallize. The PEOX based urethane triblocks were synthesized through reacting the tailblocks with the monomers for the center block whereas the PEO/PPO based polyurethaneurea was synthesized through forming the central urethane block with pendant acid groups first and then terminating the copolymer with the monofunctional copolymer. Terminal amine groups on the PEO/PPO tailblock afforded a triblock linked with two urea groups. The new polyurethanes with the PEOX tailblocks and the new polyurethaneurea with the PEO/PPO tailblocks could be utilized to efficiently stabilize magnetite nanoparticles in water. / Master of Science

Ce travail de thèse décrit l'élaboration de copolymères amphiphiles obtenus par couplage de deux homopolymères. La synthèse des copolymères s'est effectuée en deux étapes. Dans un premier temps, des homopolymères de type poly(2-méthyl-2-oxazoline) (P(MOx)) et poly(acrylate de tert-butyle) (P(At-Bu)) ont été préparés par polymérisation par ouverture de cycle cationique (CROP) et par polymérisation radicalaire contrôlée de type RAFT ou ATRP, respectivement. Puis les copolymères amphiphiles diblocs ont finalement été obtenus par une réaction de couplage polymère-polymère de type cycloaddition de Huisgen. Une étude physico-chimique de ces copolymères dans l'eau a mis en évidence la présence d'agrégats qui présentent une morphologie sphérique, des tailles inférieures à 100 nm et des concentrations d'agrégation critique de l'ordre de 10-6 mol.L-1.Les connaissances acquises sur la synthèse et l'étude des copolymères à blocs amphiphiles ont également permis le développement de copolymères greffés amphiphiles poly(-caprolactone)-g-poly(2-méthyl-2-oxazoline) (PCL-g-P(MOx)), constitués d'un bloc hydrophobe PCL sur lequel des chaînes hydrophiles P(MOx) ont été greffées. L'étude du comportement de ces copolymères dans l'eau montre la formation d'agrégats avec des caractéristiques proches de celles obtenues pour les copolymères diblocs amphiphiles. Un autre point intéressant est que la P(MOx) permet de solubiliser la PCL dans l'eau.Ces deux études illustrent l'apport de la chimie macromoléculaire pour la préparation de structures amphiphiles parfaitement définies qui s'organisent en phase aqueuse en agrégats. Ces derniers pourraient notamment être utilisés dans le domaine biomédical. / This manuscript deals with the synthesis of amphiphilic diblock copolymers obtained by the coupling of both hydrophobic and hydrophilic homopolymers. The copolymers were achieved in two steps. On the one hand, homopolymers poly(2-methyl-2-oxazoline) P(MOx)s and poly(tert-butyl acrylate)s (P(At-Bu) were synthesized by cationic ring opening polymerization (CROP) and by Reversible Addition-Fragmentation Transfer (RAFT) polymerization and atom transfer radical polymerization (ATRP), respectively. Finally, amphiphilic diblock copolymers were achieved by Huisgen's cycloaddition. Physical chemistry studies in water proved the formation of aggregates. The latter had a spherical morphology, sizes below 100 nm and critical aggregation concentration around 10-6 mol.L-1.Knowledge acquired on the synthesis and the study of amphiphilic block copolymers led to the development of poly(-caprolactone)-g-poly(2-methyl-2-oxazoline) (PCL-g-P(MOx)) amphiphilic graft copolymers, made of a hydrophobic PCL grafted with hydrophilic P(MOx) moieties. The study of aqueous solution of such copolymers showed the formation of aggregates with characteristics close from those obtained for the diblock copolymers. Another interesting point is that P(MOx) permitted the solubilization of PCL in water.The reported work illustrated the importance of macromolecular chemistry for the obtaining of amphiphilic copolymers with controlled molecular weight and narrow molar mass distributions which self-assemble in water. Such kind of materials could be used in the biomedical field.

This work aims towards the development of a modular system for fabrication of monodisperse microgels made of poly(2-oxazoline)s for use in the field of regenerative therapy.

Poly(ethylene oxide) (PEO) and poly(2-ethyl-2-oxazoline) (PEOX) are biocompatible polymers that act as hydrophilic "stealth" drug carriers. As block copolymers, the PEOX group offers a wider variety of functionalization. The goal of this project was to synthesize a poly(ethylene oxide)-b-poly(2-ethyl-2-oxazoline) (PEO-b-PEOX) block copolymer and functionalize pendent groups of PEOX with phosphonic acid. This was achieved through cationic ring opening polymerization (CROP) of 2-ethyl-2-oxazoline monomer onto PEO. These polymerizations used tosylsulfonyl chloride as initiator. Size-exclusion chromatography (SEC) was used to determine the molecular weights of the block copolymers. Two samples of 1:2 and one sample of 1:3 of PEO-to-PEOX block copolymers were made. These samples underwent partial hydrolysis of the PEOX pendent groups to form the random block copolymer, poly(ethylene oxide)-b-poly(2-ethyl-2-oxazoline)-co-poly(ethyleneimine) (PEO-b-PEOX-co-PEI). These reactions showed that there was a degree of control based on the moles of acid. Diethyl vinyl phosphonate was attached to the nitrogen of PEI units via Michael addition where the phosphorylation left <1% of PEI units unattached. The ethyl groups on the phosphonates were further hydrolyzed off phosphonate with HCl acid leaving phosphonic acid. After each step of synthesis, structures and composition were confirmed using ¹H NMR. Due to the nature of the phosphonic acid, the polymer can be utilized in the incorporation and release of cationic drugs. / Master of Science

This dissertation focuses on the synthesis and characterization of functional poly(2-ethyl-2-oxazoline) (PEtOx) containing homo- and block copolymers that are potential materials for membrane-based water purification and gas separation, drug delivery, magnetic resonance imaging and tissue engineering applications. The polymerization of 2-ethyl-2-oxazoline (EtOx) was investigated with regard to the effects of initiator structures and reaction parameters such as polymerization time and temperature on molecular weight control and molecular weight distribution, endgroup functionality, living characteristics, and mechanism and kinetics. The structure of initiators was shown to significantly affect the molecular weight control and molecular weight distribution of PEtOx oligomers. Methyl triflate initiated polymerizations were found to result in oligomers with low polydispersity (PDI) values around 1.10-1.15 and symmetrical chromatograms were obtained via size exclusion chromatography (SEC) studies with the use of refractive index, light scattering and viscosity detectors. However, EtOx polymerizations initiated by halide containing initiators such as benzyl chloride, dibromo- and diiodo-p-xylene, and vinylsilylpropyl iodides yielded PEtOx oligomers with higher PDI values ~ 1.30-1.40. Higher molecular weight distributions can be attributed to the presence of covalent species during polymerization and slower initiation rate as evidenced by kinetic studies when compared to PEtOx prepared from methyl triflate initiators. In all cases, termination reactions with aliphatic cyclic amines were quantitative. Mono- and diamine functional PEtOx oligomers with controlled molecular weight and excellent end-group functionality may be used as prepolymers for incorporation into multiblock and graft copolymer and crosslinked structures for a variety of applications such as membranes and hydrogels for tissue engineering matrices. Poly(2-ethyl-2-oxazoline) containing block copolymers were prepared using the macroinitiator method. First, amphiphilic triblock copolymers with hydrophobic poly(arylene ether sulfone) (PSF) central block and hydrophilic PEtOx side blocks were synthesized via polymerization of EtOx sequences from tosylate functional telechelic PSF macroinitiators. PSFs are well-known engineering thermoplastics with excellent resistance to hydrolysis and oxidation, as well as displaying good mechanical properties, thermal stability and toughness. Phenol functional PSFs were prepared via step-growth polymerization of dichlorodiphenylsulfone and bisphenol-A (slight excess) monomers. Phenolic chain ends were then converted to aliphatic hydroxyethyl endgroups by reaction with ethylene carbonate. Upon treatment with p-toluenesulfonyl chloride, tosylate functional PSF macroinitiators were prepared. PEtOx-b-PSF-b-PEtOx triblock copolymers (pendent acyl groups of PEtOx side blocks) were partially hydrolyzed in an acidic medium to introduce random charged poly(ethylene imine) units to prepare ionomer structures that may show good salt rejection, water flux and antibacterial properties for membrane-based water purification applications. Phosphonic acid modified poly(ethylene oxide)-b-poly(2-ethyl-2-oxazoline) (PEO-b-PEtOx) diblock copolymers were prepared via cationic ring opening polymerization of EtOx monomers from tosylate functional PEO macroinitiators and subsequent functionalization reactions on the polyoxazoline block. Post-modification reactions included controlled partial pendent acyl group hydrolysis under an acidic medium to form the random block copolymers of PEtOx and poly(ethyleneimine) (PEI), Michael addition of diethylvinyl phosphonate groups to PEI units and hydrolysis of the ethyl groups on the phosphonates to yield pendent phosphonic acid groups on the polyoxazoline block. After each step of functionalization reactions, structures and compositions were confirmed utilizing 1H NMR and the degree of phosphorylation was found to be > 95%. Both PEO and PEtOx are biocompatible polymers and the anionic quality of the phosphonic acid has the potential to be pH controllable and provide an environment where cationic drugs and contrast agents can be attached. Thus, these polymers have potential as drug carriers and contrast enhancement agents for magnetic resonance imaging applications. / Ph. D.

Im Rahmen dieser Arbeit wurden für die Herstellung neuartiger funktioneller Oberflächenbeschichtungen Polymerbürstensysteme basierend auf linearen, thermoresponsiven Poly-2-oxazolinen (POX) entwickelt und ausführlich charakterisiert. Als Grundbaustein für die Herstellung von POX-Bürsten wurden drei endfunktionalisierte thermoresponsive POX mittels kationisch ringöffnender Polymerisation synthetisiert, wobei jeweils 2-Cyclopropyl-2-oxazolin (cPrOX) als thermoresponsive Wiederholungseinheit und 2-Methyl-2-oxazolin (MeOX) als hydrophiles Comonomer zu verschiedenen Anteilen verwendet wurden. Mittels VIS-spektroskopischen Trübungsmessungen wurde für alle POX in Wasser ein LCST-Entmischungsverhalten mit einem reversiblen und scharfen Phasenübergang nachgewiesen, wobei die Trübungstemperaturen stark von der Polymerhydrophilie sowie der Molmasse und der Polymerkonzentration in Lösung abhingen. Die Herstellung der POX-Polymerbürsten auf der Basis der synthetisierten POX erfolgte über einen „grafting to“-Ansatz, bei welchem die Polymere in einem thermisch initiierten Prozess über ein funktionalisiertes Kettenende kovalent an ein Substrat angebunden wurden. Als Hauptmethode zur Charakterisierung der physikochemischen Eigenschaften der hergestellten Schichten, insbesondere deren temperaturabhängiges Schaltverhalten in Wasser, wurde spektroskopische Ellipsometrie verwendet. Zusätzlich kamen Rasterkraftmikroskopie, Kontaktwinkel und Quarzkristallmikrowaage mit Dissipationsaufzeichnung zum Einsatz. Im Gegensatz zum sehr scharfen, diskontinuierlichen Phasenübergang der POX in Lösung konnte für alle POX-Bürsten ein kontinuierlicher Übergang von einem gestreckten Bürstenzustand bei niedrigen Temperaturen in einen kollabierten Zustand bei hohen Temperaturen bestimmt werden, wobei das Quellvermögen und die temperaturabhängigen Quellkurvenverläufe durch die Polymereigenschaften und die Bürstenparameter beeinflussbar waren. Durch die Kombination eines POX mit Polyacrylsäure (PAA) als zweite Komponente konnten zudem neuartige binäre Polymerbürstensysteme hergestellt werden, welche ein komplexes pH- und temperaturabhängiges Schaltverhalten sowie ein steuerbares Proteinadsorptionsvermögen in Abhängigkeit von der Bürstenpräparationsmethodik, der POX-PAA-Zusammensetzung sowie der Temperatur und dem pH-Wert der umgebenden Pufferlösung aufwiesen. Zur ausführlichen Charakterisierung der Schichteigenschaften wurde neben den bereits benannten Methoden der spektroskopischen Ellipsometrie, Rasterkraftmikroskopie und der Kontaktwinkelmessung auch Röntgenphotoelektronenspektroskopie genutzt. Abschließende Zelladhäsionsexperimente mit humanen mesenchymalen Stammzellen auf den bürstenmodifizierte Oberflächen unter physiologischen Bedingungen offenbarten deutliche Unterschiede in der Affinität der Zellen zur Adhäsion auf POX-Homopolymerbürsten in Abhängigkeit der Bürstenhydrophilie. Darüber hinaus konnte die Zelladhäsion auch auf POX-PAA-Mischbürstensystemen gesteuert werden.

Funktionalisierte Poly(2-oxazoline) als neue Materialien stellen sowohl unter strukturellen Gesichtspunkten als auch im Hinblick auf potentielle Anwendungen eine interessante Polymerklasse dar. Die Ausbildung von hierarchischen Strukturen mit Poly(2-oxazolinen) über intermolekulare Wasserstoffbrückenbindungen ist hierbei ein bisher nicht beachteter Aspekt. Über einen bioinspirierten Ansatz sollten gezielt funktionelle Gruppen, die für einen hierarchischen Aufbau, z.B. in Proteinen, verantwortlich sind, in vereinfachter Weise auf die synthetische Substanzklasse der Poly(2-oxazoline) übertragen werden. Die vorliegende Arbeit beschäftigt sich mit der modularen Synthese neuer, funktionalisierter Poly(2-oxazolin) Homo- und Copolymere. Ausgehend von der Synthese von 2-(3-Butenyl)-2-oxazolin wurden definierte Präpolymere in einer kationischen Isomerisierungspolymerisation unter kontrolliert/„lebenden“ Bedingungen hergestellt. In einer anschließenden „Thio-Click“ (Thiol-En-Reaktion) Modifizierungsreaktion wurden die gewünschten funktionellen Gruppen quantitativ eingeführt. Hydroxylierte Poly(2-oxazoline) wurden hinsichtlich ihres Aggregationsverhaltens in Wasser untersucht. Bereits die jeweiligen Homopolymere bildeten aufgrund von intermolekularen Wasserstoffbrückenbindungen supramolekulare tubuläre Nanofasern aus. Durch Einsatz verschiedener analytischer Methoden konnte die innere Struktur der Nanoröhren beschrieben und ein entsprechendes Modell aufgestellt werden. Die dargestellten funktionellen Poly(2-oxazoline) wurden hinsichtlich ihrer Anwendung als potentielle, synthetische „antifreeze additives“ untersucht. Alle Polymere besitzen eine ausgeprägte Tendenz zur Nukleierung von Wasser und führen daher zu signifikanten Änderungen der Eismorphologie. Des weiteren wurde ein carboxyliertes Derivat zur biomimetischen Mineralisation von Kalziumcarbonat eingesetzt und nach phänomenologischen Gesichtspunkten untersucht. / Functionalized poly(2-oxazoline)s are a promising class of materials concerning their self-assembly behavior as well as for future applications. Hierarchical structure formation based on hydrogen bonding interactions has not been investigated yet. Applying a bioinspired approach, functional groups promoting hierarchical structure formation are introduced to poly(2-oxazoline)s. This work is focused on the modular synthesis of new functionalized poly(2-oxazoline) homo and copolymers. Starting from the synthesis of the new monomer 2-(3-butenyl)-2-oxazolin, well-defined precursor materials were prepared via cationic isomerization polymerization. Next, the polymers were quantitatively modified with the aimed functional groups using a “thio-click” (thiol-ene) reaction. The aggregation behaviour of hydroxylated poly(2-oxazolines) in water was investigated. Homo- as well as block copolymers can form supramolecular hollow nanofibers via intermolecular hydrogen bonding. Using a variety of different analytical methods, the structure of the nanotubes was determined and a formation model was proposed. Furthermore, the functionalized poly(2-oxazoline)s were investigated as synthetic mimics of natural anti-freeze additives. It was found, that these polymers show the tendency to nucleate water, thus influencing the morphology of ice. Finally, a carboxylated derivative was applied as an additive for the mineralization of calcium carbonate.