A síntese e a caracterização de um novo tipo de eletrólito sólido polimérico são descritas neste trabalho. Os materiais preparados consistiram de filmes de hidroxietil celulose ou hidroxipropil celulose entrecruzadas com diisocianatos de poli(óxido de etileno) e poli(óxido de propileno) ou enxertadas com monoisocianato de poli(óxido de propileno). Todos estes isocianatos foram sintetizados a partir das respectivas aminas comerciais. Filmes de hidroxietil celulose entrecruzada com hexametileno diisocianato ou enxertados com fenil isocianato também foram estudados. Como técnicas de caracterização foram utilizadas espectroscopia no infravermelho, no ultravioleta e de ressonância magnética nuclear, análises térmicas e difração de raios-X. Os filmes dopados com LiClO4 foram caracterizados utilizando-se as mesmas técnicas e a condutividade foi determinada através do método de impedância complexa. Os resultados foram da ordem de 10-5 Scm-1 a 60oC. Este valor permitiu concluir que as cadeias de derivado de celulose parecem não influenciar no fenômeno de condução; aparentemente este encontra-se mais relacionado ao tipo de isocianato utilizado na formação do filme. Os resultados de condutividade e de mobilidade de cadeia polimérica indicam que os sistemas aqui estudados podem ser aplicados como eletrólitos sólidos poliméricos. Os filmes com isocianatos comerciais, no entanto não apresentaram resultado de condução interessante. / The synthesis and characterization of new types of solid polymer electrolytes based on hydroxyethyl and hydroxypropyl cellulose grafted with different polyethers were investigated. The synthesis is based on the reaction between the cellulose derivative and mono and difunctional isocyanates prepared from amines of polyethylene oxide and polypropylene oxide. It were also synthesized films of hydroxyethyl cellulose grafted with hexamethylene diisocyanate and phenylisocyanate. These materials were characterized through techniques of infrared, ultraviolet and nuclear magnetic ressonance spectroscopies, thermal analysis and X-ray diffraction. The films of polysaccharide and polyether that contained LiClO4 showed conductivity values of the order of 10-5 Scm-1 at 60oC. The value of this parameter seems to be independent of the cellulose derivative parameters and it is better related to the type of isocyanate grafted on the polysaccharide chain. The conductivity and chain mobility results show that the systems studied here can be applied as solid polymer electrolytes. The materials synthesized using commercial isocyanates as grafting reactant did not show interesting conductivity response.

Given the occurrence and diversity of nitrogen-containing molecules, the development of new amination methods is of significant importance. Indeed, a recent study shows that 60% of the FDA approved drugs contain a nitrogen heterocycle. Undoubtedly, novel methodologies arising for uncommon intermediates for the incorporation of nitrogen atoms are needed to access more complex molecules. The present document focus on the development of new methods for the formation of C-N and N-N bonds for the synthesis of acyclic and heterocyclic products. Isocyanates are useful synthons and reactive intermediates. To overcome their toxicity and instability, blocked (or masked) isocyanates have been developed: an equilibrium generates the isocyanate in-situ, allowing for safer precursors and better control over the concentration of the reactive isocyanate. This strategy enables the development of new reactivity, particularly for heteroatom-substituted isocyanates. However, reactions of oxygen-substituted isocyanates (O-isocyanates) remained severely underdeveloped. In Chapter 2, bench-stable N-oxy-carbamates and N-oxyureas are reacted under basecatalysis or thermal conditions to form the corresponding O-isocyanate intermediate in situ. In the first part of this chapter, a survey was performed and optimum experimental conditions for the controlled formation of O-isocyanate intermediates from the block precursors were found. Gratifyingly, the known side-reactions of O-isocyanates (trimerization and 1,2-shift) were avoided and different nucleophiles and substituents were studied for the controlled formation of N-oxyureas via substitution reaction of blocked O-isocyanates. Cascade reactions provided the opportunity to further develop this controlled reactivity of O-isocyanates. Herein, the first cascade-reaction of O-isocyanates is portrayed using - and -aminoester as the partners for the synthesis of hydantoin and dihydrouracil derivatives (>30 examples). Moreover, the conditions were modified to perform the reaction with -alcohol and - thioesters. Finally, evidence for the O-isocyanate intermediate is provided.

The aim of this thesis was the application of the functional prepolymer NCO-sP(EO-stat-PO) for the development of new biomaterials. First, the influence of the star-shaped polymers on the mechanical properties of biocements and bone adhesives was investigated. 3-armed star-shaped macromers were used as an additive for a mineral bone cement, and the influence on the mechanical properties was studied. Additionally, a previously developed bone adhesive was examined regarding cytocompatibility. The second topic was the examination of novel functionalization steps which were performed on the surface of electrospun fibers modified with NCO-sP(EO-stat-PO). This established method of functionalizing electrospun meshes was advanced regarding the modification with proteins which was then demonstrated in a biological application. Two different kinds of antibodies were immobilized on the fiber surface in a consecutive manner and the influence of these proteins on the cell behavior was investigated. The final topic involved the quantification of surface-bound peptide sequences. By functionalization of the peptides with the UV-reactive molecule 2-mercaptopyridine it was possible to quantify this compound via UV measurements by cleavage of disulfide bridges and indirectly draw conclusions about the number of immobilized peptides. In the field of mineral biocements and bone adhesives, NCO-sP(EO-stat-PO) was able to influence the setting behavior and mechanical performance of mineral bone cements based on calcium phosphate chemistry. The addition of NCO-sP(EO-stat-PO) resulted in a pseudo-ductile fracture behavior due to the formation of a hydrogel network in the cement, which was then mineralized by nanosized hydroxyapatite crystals following cement setting. Accordingly, a commercially available aluminum silicate cement from civil engineering could be modified. In addition, it could be shown that the use of NCO-sP(EO-stat-PO) is beneficial for adjusting specific material properties of bone adhesives. Here, the crosslinking behavior of the prepolymer in an aqueous medium was exploited to form an interpenetrating network (IPN) together with a photochemically curing poly(ethylene glycol) dimethacrylate (PEGDMA) matrix. This could be used for the development of a bone adhesive with an improved adhesion to bone in a wet environment. The developed bone adhesive was further investigated in terms of possible influences of the initiator systems. In addition, the material system was tested for cytocompatibility by using different cell lines. Moreover, the preparation of electrospun fiber meshes via solution electrospinning consisting of poly(lactide-co-glycolide) (PLGA) as a backbone polymer and NCO-sP(EO-stat-PO) as functional additive is an established method for the application of the meshes as a replacement of the native extracellular matrix (ECM). In general, these fibers reveal diameters in the nanometer range, are protein and cell repellent due to the hydrophilic properties of the prepolymer and show a specific biofunctionalization by immobilization of peptide sequences. Here, the isocyanate groups presented on the fiber surface after electrospinning were used to carry out various functionalization steps, while retaining the properties of protein and cell repellency. The modification of the electrospun fibers involved the immobilization of analogs or antagonists of tumor necrosis factor (TNF) and the indirect detection of these by interaction with a light-producing enzyme. Here, a multimodal modification of the fiber surface with RGD to mediate cell adhesion and two different antibodies could be achieved. After culturing the cell line HT1080, the pro- or anti-inflammatory response of cells could be detected by IL-8 specific ELISA measurements. Furthermore, the quantification of molecules on the surface of electrospun fibers was investigated. It was tested whether the detection by means of super-resolution microscopy would be possible. Therefore, experiments were performed with short amino acid sequences such as RGD for quantification by fluorescence microscopy. Based on earlier results, in which a UV-spectrometrically active molecule was used to detect the quantification of RGD, it was shown that short peptides can also be quantified in a small scale on flat functional substrates (2D) such as NCO-sP(EO-stat-PO) hydrogel coatings, and modified electrospun fibers produced from PLGA and NCO-sP(EO-stat-PO) (3D). In addition, a collagen sequence was used to prove that a successful quantification can be carried out as well for longer peptide chains. These studies have revealed that NCO-sP(EO-stat-PO) can serve as a functional additive for many applications and should be considered for further studies on the development of novel biomaterials. The rapid crosslinking reaction, the resulting hydrogel formation and the biocompatibility are to be mentioned as positive properties, which makes the prepolymer interesting for future applications. / Ziel der Arbeit war die Anwendung der funktionalen Präpolymere NCO-sP(EO-stat-PO) für die Entwicklung von neuen Biomaterialien. Als erstes wurde untersucht, welchen Einfluss die sternförmigen Polymere auf die mechanischen Eigenschaften von Biozementen und Knochenadhäsiven haben. Beispielsweise wurden 3-armige Macromere als Additive für einen mineralischen Knochenzement verwendet und dessen mechanische Eigenschaften untersucht. Außerdem wurde ein kürzlich entwickelter NCO-sP(EO-stat-PO) haltiger Knochenklebers auf Zytokompatibilität getestet. Ein zweites Kapitel beinhaltete die Modifikation von elektrogesponnenen Polymerfasern mit NCO-sP(EO-stat-PO) basierend auf einer etablierten Methode. Es wurde untersucht, welche weiteren Funktionalisierungen auf solchen Oberflächen vorgenommen werden können. Diese Modifizierungsschritte wurden in einer biologischen Anwendung demonstriert, indem verschiedene Antikörper aufeinanderfolgend auf der Faseroberfläche gebunden wurden. Der Einfluss dieser Proteine auf das Verhalten von Zellen auf diesen Oberflächen wurde untersucht. Als letztes wurde die Quantifizierung von oberflächengebundenen Peptidsequenzen demonstriert. Mittels Funktionalisierung der Peptide mit dem UV-reaktiven Molekül 2-Mercaptopyridin konnte durch Spaltung von Disulfidbrücken diese Verbindung UV-metrisch quantifiziert und indirekt Rückschlüsse auf die Anzahl der immobilisierten Peptide gezogen werden. Durch den Zusatz von NCO-sP(EO-stat-PO) konnten das Abbindeverhalten und die mechanischen Eigenschaften von mineralischen Calciumphosphat-Knochenzementen moduliert werden. Der Zusatz von 3-armigem, sternförmigem NCO-sP(EO-stat-PO) führte dabei zu einem pseudoduktilen Bruchverhalten durch Bildung eines Hydrogelnetzwerks im Zement, das anschließend durch die Zementreaktion mit nanoskaligem Hydroxylapatit mineralisiert wurde. Im Bereich mineralischer Knochenzemente und Adhäsive konnte gezeigt werden, dass NCO-sP(EO-stat-PO) zur Einstellung der Eigenschaften verwendet werden kann. Hierbei wurde dessen Quervernetzungsverhalten im wässrigen Medium ausgenutzt, um mit einer photochemisch härtenden Polyethylenglykoldimethakrylat (PEGDMA) Matrix interpenetrierende Netzwerke (IPNs) zu bilden. Diese konnten für die Entwicklung eines Knochenklebers mit verbesserter Haftung auf Knochen im feuchten Milieu genutzt werden. Das kürzlich entwickelte Knochenadhäsiv wurde im Hinblick auf den Einfluss des Initiatorsystems untersucht. Außerdem wurde die Zytokompatibilität des Materials anhand verschiedener Zelltypen getestet. Die Herstellung von elektrogesponnenen Faservliesen mittels Solution Electrospinning aus Polylactid-co-Glycolid (PLGA) als Gerüst-bildendem Polymer und NCO-sP(EO-stat-PO) als funktionalem Additiv ist eine etablierte Methode, um diese Vliese zur Nachbildung nativer Extrazellulär-Matrix anzuwenden. Die Fasern weisen einen Durchmesser im Nanometer-Bereich auf, sind proteinabweisend durch die hydrophilen Eigenschaften des Präpolymers und können durch Immobilisierung von Peptidsequenzen spezifisch biofunktionalisiert werden. Hierbei wurden die Isocyanate auf der Faseroberfläche genutzt, um verschiedenste Funktionalisierungsschritte unter Beibehaltung der protein- und zellabweisenden Eigenschaften auszuführen. Die Modifizierung der elektrogesponnenen Fasern beinhaltete die Immobilisierung von Analoga oder Antagonisten des Tumornekrosefaktors (TNF) sowie den indirekten Nachweis über eine Lichtreaktion. Hierbei konnte eine multimodale Modifizierung der Faseroberfläche mit RGD-Sequenzen zur Vermittlung der Zelladhäsion und zwei verschiedenen Antikörpern erreicht werden. Nach Kultivierung der Zelllinie HT1080 konnte die pro- oder antiinflammatorische Antwort der Zellen mittels IL-8 spezifischem ELISA nachgewiesen werden. Eine weitere Fragestellung war der Quantifizierung von Molekülen auf der Oberfläche von elektrogesponnen Fasern gewidmet. Es wurde getestet, ob ein Nachweis mittels hochauflösender Mikroskopie möglich ist. Hierzu wurden RGD-Sequenzen zur fluoreszenzmikroskopischen Quantifizierung verwendet. Basierend auf früheren Ergebnissen, bei denen für die Quantifizierung von RGD ein UV-aktives Molekül genutzt wurde, konnte gezeigt werden, dass sich kurze Peptide auch im kleinen Maßstab auf flachen Substraten (2D) wie Hydrogel-Beschichtungen aus NCO-sP(EO-stat-PO) als auch auf elektrogesponnenen Fasern aus PLGA und NCO-sP(EO-stat-PO) (3D) quantifizieren lassen. Außerdem wurde eine Kollagen-Sequenz als längere Peptidkette herangezogen, um auch hier eine erfolgreiche Quantifizierung zu beweisen. Es konnte gezeigt werden, dass NCO-sP(EO-stat-PO) als funktionales Additiv für viele Anwendungen dienen kann und für weitere Untersuchungen zur Entwicklung von Biomaterialien berücksichtigt werden sollte. Die schnelle Quervernetzungsreaktion, die resultierende Hydrogelbildung und die Biokompatibilität sind als positive Eigenschaften zu nennen, die das Präpolymer für zukünftige Anwendungen interessant macht.

Nitrenes are reactive intermediates for many organic reactions, such as Curtius rearrangement. The thermo- or photochemical- decomposition of azides or isocyanates was known to generate nitrenes. We investigated the thermal chemistry of nitrene adsorbed on Cu(111) using benzyl azide (Bz-N=N=N), benzyl isocyanate (Bz-N=C=O) and phenyl isocyanate (ph-N=C=O) as precursors under ultrahigh vacuum conditions using temperature-programmed reaction/desorption (TPR/D), reflectionabsorption infrared spectroscopy (RAIRS) and X-ray photoelectron spectroscopy (XPS). Our study shows that despite of the isoelectronic functionalities (-N=N=N vs. -N=C=O) these molecules undergo different reaction pathways. For benzyl azide (Bz-N=N=N), the azido group losses N2 ,and the phenyl group migrates from nitrogen to carbon, forming surface bound H2C=N-Ph at 210 K. Eventually, H2 elimination and a carbon-to-nitrogen phenyl shift give the thermally stable ph-CN final product. XPS reveals that benzyl isocyanate (Bz-N=C=O) rearranges to form amide intermediate on the surface, which breaks into CO2, HCN and toluene at 410 K. RAIRs suggests that phenyl isocyanate (ph-N=C=O) undergoes cyclodimerization, cyclotrimerization and condensation to remove CO2 at 170 K, and phenyl group shifts from nitrogen to carbon to produce a metal bound acyl nitrene species (Ph-(C=O)-N---Cu) at 410 K.

Techn. Universiẗat, Diss., 2007--Darmstadt.

A síntese e a caracterização de um novo tipo de eletrólito sólido polimérico são descritas neste trabalho. Os materiais preparados consistiram de filmes de hidroxietil celulose ou hidroxipropil celulose entrecruzadas com diisocianatos de poli(óxido de etileno) e poli(óxido de propileno) ou enxertadas com monoisocianato de poli(óxido de propileno). Todos estes isocianatos foram sintetizados a partir das respectivas aminas comerciais. Filmes de hidroxietil celulose entrecruzada com hexametileno diisocianato ou enxertados com fenil isocianato também foram estudados. Como técnicas de caracterização foram utilizadas espectroscopia no infravermelho, no ultravioleta e de ressonância magnética nuclear, análises térmicas e difração de raios-X. Os filmes dopados com LiClO4 foram caracterizados utilizando-se as mesmas técnicas e a condutividade foi determinada através do método de impedância complexa. Os resultados foram da ordem de 10-5 Scm-1 a 60oC. Este valor permitiu concluir que as cadeias de derivado de celulose parecem não influenciar no fenômeno de condução; aparentemente este encontra-se mais relacionado ao tipo de isocianato utilizado na formação do filme. Os resultados de condutividade e de mobilidade de cadeia polimérica indicam que os sistemas aqui estudados podem ser aplicados como eletrólitos sólidos poliméricos. Os filmes com isocianatos comerciais, no entanto não apresentaram resultado de condução interessante. / The synthesis and characterization of new types of solid polymer electrolytes based on hydroxyethyl and hydroxypropyl cellulose grafted with different polyethers were investigated. The synthesis is based on the reaction between the cellulose derivative and mono and difunctional isocyanates prepared from amines of polyethylene oxide and polypropylene oxide. It were also synthesized films of hydroxyethyl cellulose grafted with hexamethylene diisocyanate and phenylisocyanate. These materials were characterized through techniques of infrared, ultraviolet and nuclear magnetic ressonance spectroscopies, thermal analysis and X-ray diffraction. The films of polysaccharide and polyether that contained LiClO4 showed conductivity values of the order of 10-5 Scm-1 at 60oC. The value of this parameter seems to be independent of the cellulose derivative parameters and it is better related to the type of isocyanate grafted on the polysaccharide chain. The conductivity and chain mobility results show that the systems studied here can be applied as solid polymer electrolytes. The materials synthesized using commercial isocyanates as grafting reactant did not show interesting conductivity response.

No description available.

Cette thèse porte sur la conception de carbonates cycliques originaux et d’amines dérivés des huiles végétales dans le but de synthétiser des poly(hydroxyuréthane)s entièrement bio-sourcés. D’une part, deux voies d’accès à des amines dérivées d’acides gras utilisant des conditions douces ont été étudiées. La première consiste en l’oxydation sous air d’alcools aliphatiques en nitriles en présence de TEMPO supporté sur silice, suivi par une hydrogénation des dinitriles en diamines. Egalement, des diènes dérivés d’acides gras ont été couplés à la cystéamine via une chimie thiol-ène, permettant l’accès à des diamines aliphatiques bio-sourcées. D’autre part, des carbonates cycliques substitués à 5 chaînons ont été synthétisés à partir de dérivés d’acides gras et de glycérol, dans le but d’augmenter leur réactivité vis-à-vis de l’aminolyse. En insérant un groupement fonctionnel éther, thio-éther ou ester en position α ou β des carbonates cycliques, la réactivité de ces derniers vis-à-vis des amines a pu être ajustée. L’étude de la sélectivité, des réactions secondaires et de la catalyse de la voie carbonate/amine a été menée afin de mieux appréhender cette voie d’accès à des polyuréthanes sans isocyanates. Des poly(hydroxyuréthane)s entièrement oléo-sourcés ont été synthétisés avec succès, montrant des propriétés physico-chimiques contrôlables selon la structure des monomères. / In this thesis, vegetable oils were used as a platform to design original cyclic carbonates and amines with the goal to synthesize fully bio-based poly(hydroxyurethane)s. On the one hand, two routes to fatty acid-based amines were implemented in mild conditions. First, the oxidation of aliphatic alcohols into nitriles was performed under air in the presence of supported TEMPO on silica, followed by hydrogenation of nitrile compounds into corresponding amines. Second, thiol-ene chemistry was performed on unsaturated fatty acid substrates to design original aliphatic bio-based diamines. On the other hand, substituted 5-membered cyclic carbonates were designed from fatty acids and glycerol derivatives to enhance their reactivity towards aminolysis. By inserting ether, thio-ether or ester functionalities in α- or β-position of the cyclic carbonates, their reactivity towards amines could be tuned. Investigations on the selectivity, side reactions and catalysis of the carbonate-amine reaction were carried out to apprehend this route to non-isocyanate polyurethanes. Fully vegetable oil-based PHUs with tunable physico-chemical properties with respect to the monomer structures could be easily achieved.

De nos jours, parmi toutes les transformations chimiques dont disposent les chimistes organiciens, le réarrangement sigmatropique [3,3] constitue un outil puissant afin de créer une liaison C-C ou encore C-hétéroatome. Le réarrangement d’allyl cyanate en allyl isocyanate, jusqu’ici peu utilisé, est en train d’émerger, comme une nouvelle méthode efficace de préparation d’allylamines substituées. C’est dans ce contexte que s’inscrit mon travail de thèse qui a pour objectif d’étudier et d’utiliser le réarrangement sigmatropique [3,3] d’allyl cyanates diversement substitués pour la synthèse de molécules d’intérêt biologique. Dans une première partie, l’emploi d’allyl cyanates borylés nous a permis de synthétiser, de façon stéréocontrôlée, des ènecarbamates et des ènehydroxyurées cycliques à 7 chainons ainsi que des γ-butyrolactones. Cette méthodologie a été appliquée à la première synthèse totale de la (-)-Galbacin. Les ènecarbamates cycliques ont fait l’objet, en seconde partie, d’une étude structure-activité en tant qu’inhibiteur du protéasome humain. Dans une troisième partie, nous avons étudié le réarrangement d’allyl cyanates silylés ce qui nous a permis d’accéder à des α-amino allylsilanes énantioenrichis. En dernière partie, nous avons mis en évidence un oxo-réarrangement à partir d’allyl carbamates substitués par un groupement aryle. / Nowadays, among all chemical transformations in the organic chemist’s toolbox, [3,3] sigmatropic rearrangements represent a powerful method to create carbon-carbon or even carbon-heteroatom bonds. The allyl cyanate to allyl isocyanate rearrangement, underused so far, is becoming an attractive method to prepare substituted allylamines. In this context, I studied and applied in my thesis this [3,3] rearrangement on diversely substituted allyl cyanates for the synthesis of molecules of biological interest. First, we used borylated allyl cyanates to prepare, stereoselectively, cyclic seven membered enecarbamates and enehydroxyureas as well as γ-butyrolactones. This methodology was applied to the first total synthesis of (-)-Galbacin. Then, a library of cyclic enecarbamates was performed to study the structure-activity relationship on the human proteasome. Next, the study of silylated allyl cyanates allowed us to prepare some new enantioenriched α-amino allylsilanes. Finally, we brought to light an unexpected oxo-rearrangement from aryl substituted allyl carbamates.

Au cours de ces trente dernières années, les allylboranes, une classe particulière de composés organoborés, ont pris une place particulièrement importante en synthèse organique, principalement dans la synthèse stéréocontrôlée d'alcools homoallyliques par addition sur un aldéhyde. C'est dans ce contexte que s'inscrit mon travail de thèse qui a pour objectif la mise au point de voies d'accès originales à deux familles d'allylboronates alpha-hétérosubstitués et à l'étude de leur réactivité. Pour cela, nous nous sommes intéressés dans un premier temps au comportement de gamma-borylallylsilanes vis à vis de diverses espèces électrophiles, ce qui a permis d'accéder notamment à des alpha-fluoroallylboronates, précurseurs de (Z)-1-fluoro-1-alcènes et à des fluorures allyliques. D'autres électrophiles, hétéroatomiques ou carbonés, peuvent être utilisés pour conduire après refonctionnalisation par addition sur des aldéhydes à des alcools insaturés de structures variées. Dans une seconde partie, nous avons synthétisé des alpha-isocyanatoallylboronates par réarrangement sigmatropique [3,3] d'allylcyanates borylés. Ces intermédiaires réactionnels, particulièrement intéressants pour accéder en série optiquement active à des ènecarbamates cycliques à sept chaînons, sont également précurseurs de pyrrolidines tétrasubstituées selon un réarrangement jusqu'alors non décrit dans la littérature. / Over the last thirty years, allylboranes, a particular class of organoboron compounds, have found many valuable applications in organic synthesis, mainly in the stereoselective synthesis of homoallylic alcohols via addition to aldehydes. In this context, we have developed two novel families of alpha-heterosubstituted allylboronates. We first studied the behavior of gamma-borylallylsilanes towards various electrophilic species in order to access to alpha-fluoroallylboronates which are versatile precursors of various fluorinated molecules. Other heteroatom or carbon electrophiles could also be used to afford after refunctionalization with aldehydes structurally diverse unsaturated alcohols. In the second part of this thesis, we studied the reactivity of alpha-isocyanatoallylboronates prepared by [3,3] sigmatropic rearrangement of borylated allylcyanates. These intermediates have proven to be particularly useful to synthesize optically active cyclic seven membered enecarbamates and tetrasubstituted pyrrolidines.