Search

Dissertation, RWTH Aachen University, 2022; Aachen : RWTH Aachen University 1 Online-Ressource : Illustrationen, Diagramme (2023). = Dissertation, RWTH Aachen University, 2022, This thesis concerns itself with the synthesis of oxazolidinones and polyoxazolidinones from the corresponding epoxides and isocyanates. The oxazolidinone moiety is applied widely as constituent of antibiotics and auxiliaries in enantioselective organic synthesis. Because of the readily available raw materials, the oxazolidinone building block is likewise of interest for the synthesis of polyoxazolidinone-based high-performance thermoplastics. As will be shown in this thesis, the oxazolidinone moiety is obtained readily by conversion of epoxide and isocyanate, when a suitable catalyst is applied. For application in the polymerization reaction, the catalyst not only had to provide excellent activity, but also outstanding selectivity. The approach described in this thesis is divided into two parts. The first part (Chapter II) deals with the identification of a suitable catalyst. Catalysts were assessed in a model system comprising a monofunctional epoxide and isocyanate. The focus was placed on organic Lewis acid-base catalysts, as the catalyst needed to be metal-free. Literature-known tertiary ammonium salts were the starting point. Azaspiro and imidazolium salts proved to be selective catalysts, but their activity was not adequate for industrial application. Comparing tetrabutyl ammonium with tetrabutyl phosphonium bromide salts, we found that phosphonium catalysts not only were more active, but also provided similar or enhanced selectivity. The effect of the chemical groups attached to the phosphonium center were explored in detail. Substitution of alkyl by aryl groups led to drastic increase in activity, while the high selectivity was preserved. The activity was optimized further by amending the aryl group with adequate substituents. The catalysts developed this way were then applied to the polymerization reaction of difunctional epoxides with diisocyanates. As the polyoxazolidinone synthesis was subject to the formation of various side products, the selectivity of the catalyst was a central aspect. A suitable reactor system and appropriate reaction parameters had to be defined. Successfully, we synthesized polyoxazolidinones that performed as high-performance thermoplastics. The second part of this thesis (Chapter III) focuses on the chemical and thermophysical properties of the thermoplastics that were obtained. The polyoxazolidinones were thermally highly stable with glass transition temperatures of 170-180°C and decomposition temperatures up to 400°C. First tests showed that antioxidants have a beneficial effect on the thermal stability of polyoxazolidinones at elevated temperatures. Last but not least, the application aspects were explored by spinning polymer samples into fibers., Published by RWTH Aachen University, Aachen

Monolithische Phasen werden seit ca. 20 Jahren entwickelt und sind in den letzten Jahren eine attraktive Alternative zu etablierten mit Partikeln gefüllten Säulen geworden. Sie werden in anorganische Phasen und organische Polymermonolithe unterteilt. Monolithe bestehen aus einem einzigen, durchgehenden Stück. Charakteristisch ist das sie durchziehende Porennetzwerk, durch das der Eluent mit geringerem hydraulischen Widerstand fließen kann und das somit schnellere Flussraten ermöglicht. Polymermonolithe werden vorwiegend für die Separation großer Biomoleküle aufgrund eines durch Konvektion beschleunigten Massentransfers eingesetzt. Zudem sind sie über einen breiten pH-Wert-Bereich stabil und können direkt (in situ) im gewünschten Format polymerisiert werden. In der vorliegenden Arbeit gelang die Herstellung neuartiger epoxidbasierter Phasen nach einem von Weller et al. entwickelten Konzept, die im Affinitätsexperiment angewendet wurden. Die Herstellung erfolgte durch Autopolymerisation polyfunktioneller Glycidylether. Für die Funktionalisierung wurden nicht polymerisierte Epoxide genutzt. Als Monomere dienten TEPIC, GE 100 sowie GE 500. Die Arbeiten konzentrierten sich vor allem auf die bei Raumtemperatur durchführbaren Synthesen mit dem höher funktionellen GE 500. Die Polymerisationsbedingungen wurden hinsichtlich Porogenmischung und -anteil optimiert. Eine mit 75 Vol.-% Porogen (Dioxan/ MTBE (2:3)) hergestellte und mit rProtein A funktionalisierte Kapillarsäule (66 %, 12 µm, 7m2/g) ergab im Affinitätsexperiment eine Kapazität von 0,44 mg/mL aus Kaninchenserum isolierbarem IgG. Durch Beimischung von 60 % BDE konnte der Epoxidgehalt vervierfacht und die Porengröße auf 400 nm bei 59 % Porosität reduziert werden. Die spezifische Oberfläche wurde verdreifacht und die Kapazität präparierter Disks auf 0,90 mg/mL etwa verdoppelt. Die in dieser Arbeit entwickelten Disks können zur Isolierung von IgG aus einer komplexen Probe, wie beispielsweise Blutserum, eingesetzt werden. Monolithic supports have been developed since 20 years and have become an attractive alternative to well-established columns packed with particles over the past years. They are classified into inorganic media and organic polymer monoliths. Monoliths consist of a single, continuous piece with an integrated characteristic porous network through which the eluent can flow with lower hydraulic resistance and which consequently offers higher flow rates. Due to an accelerated mass transfer caused by convection polymer monoliths are mainly used for separation of large biomolecules. In addition, they are stable over a wide pH range and can be polymerized directly (in situ) in the desired format. In the present work the successful preparation of new epoxide-based supports according to a concept introduced by Weller et al. as well as their application in affinity chromatography are reported. Their preparation was carried out by self-polymerization of polyfunctional glycidyl ethers and for functionalization non-polymerized epoxide groups were used. As monomers TEPIC, GE 100 and GE 500 were utilized. The work has focused especially on the polymerization of the higher functional GE 500, which can be perfomed at room temperature and was optimized in terms of both composition and amount of porogen. The extraction of IgG from rabbit serum with a capillary column (66 %, 12 µm, 7m2/g) prepared by 75 vol.-% porogen (dioxane/ MTBE (2:3)) and functionalized with rprotein A resulted in a capacity of 0,44 mg/mL. By addition of 60 % BDE the epoxide content was quadrupled and the pore size reduced to 400 nm while maintaining consistently high porosity of 59 %. The specific surface area was tripled and the capacity of prepared disks approximately doubled to 0,90 mg/mL. The disks developed in this work can be applied for the isolation of IgG from complex samples such as serum.

This work deals with the synthesis of defined polymers with polyethylene oxide backbone. The basic monomer is glycidol and its protected derivatives. Protected glycidols such as allyl glycidyl ether, tert.butyl glycidyl ether and especially ethoxyethyl glycidyl ether give linear polymers which can me modified chemically in a second step. The first area of research with this kind of polymers was dying of keratine fibres and cotton with pigments. In industry, dye molecules are incorporated into a fibre, while the coloring is established by permanent linking of these. If covered to a surface, the dye may be rinsed too easily; to avoid this problem, a statistical copolymer made of allyl glycidyl ether and ethoxyethyl glycidyl ether is taken and modified to a cationic polymer by appropriate methods; the final polymer works as an adhesive between pigment and fibre. The general adhesion to human hair, wool and cotton is investigated, results show that adhesion decreases in the order cotton - wool - hair. The second area of research deals with synthesis and chemophycial behaviour of block copolymers. The used blockcopolymers are synthesized of ethoxyethyl glycidyl ether and phenyl glycidyl ether, with total chain lengths in a range of 10 to 20 repeat units. Short blockcopolymers are easy to dissolve and may be used as surfactants for stabilizing of emulsions. The solubility was increased by modification of free alcohol groups to carboxymethyl groups. Stabilization of carbon black in aqueous medium was shown on semi-industrial scale. Witzh longer blocks and increased concentrations, more and more interactions occur, and self-assembly is expected. This is used in the third area of research, to obtain a defined structure on surfaces. Therefor, block copolymers of ethoxyethyl glycidyl ether and aliphatic epoxides are synthesized (with subsequent hydrolysis). The aliphatic side chains constist of 10, 12, 14 and 16 carbon atoms. Thsi gives a sufficient difference in polarity of the blocks, and the longer side chains are able to crystallize. The found structures in this work are cylinders, which are orientated parallel to the substrate surface (silicium wafers). In the last area, it is investigated if an incorporation of aldehyd groups to a linear polyglycidol is possible. The aim is the linkage of polypeptides to polymers. With the used copolymers (block and random) made of allyl glycidol ether and ethoxyethyl glycidyl ether or tert.butyl glycidyl ether it was tried if as many aldehyd groups as possibel may be generated, to end up with high degree of crosslinking even at low conversions. Synthetically, allyl groups of the polymers were treated with ozon to obtain aldehyde groups, as well as etherification of free OH groups of polyglycidol wit 2-bromomethyl-1,3-dioxolane to yield a protected aldehyde group. It was found, that both reations are not very successful.

Dipeptid-Bibliotheken mit epoxidischer Ankerfunktion wurden zur Gewinnung von Strukturinformationen über die P’-Bindungstaschen papainähnlicher Cysteinproteasen erzeugt. Die Präferenzen von Cathepsin L, B und X, sowie µ-Calpain wurden ermittelt und auf diesem Weg Inhibitoren mit erhöhter Affinität für Cathepsin L und B erhalten. Im Fall von µ-Calpain war hingegen ein von einem aus dem endogenen Inhibitor Calpastatin erhaltenen Fragment ausgehender Ansatz erfolgreicher. Es wurde ein 20-meres Peptid mit submikromolarer Hemmwirkung gefunden. Die Beteiligung der entsprechenden N- und C- Termini an der selektiven Bindung wurde mit entsprechenden Fragmenten und nicht peptidisch verbrückten Konstrukten ermittelt. Schließlich wurde die potentielle Existenz einer Typ II β-Schleife mit zyklischen homodetischen Peptiden überprüft. Das 20-mere Peptid wurde mit Photoaffinitätsmarkern versehen und zur Bestimmung des Bindungsmodus dieses neuen Inhibitors eingesetzt. Dipeptide libraries with epoxidic anchor function were produced in order to acquire structural information on the primed side binding pockets of papain-like cysteine proteases. The preferences of cathepsin L, B and X, as well as µ-calpain were investigated and inhibitors with augmented affinity for cathepsin L und B were obtained. In the case of µ-calpain, an approach based on a peptide fragment obtained from the endogenous inhibitor calpastatin was more successful. A 20-mer peptide with submicromolar inhibition capacity was found, while the N- and C-terminal parts’ share of the selective binding was elucidated with truncated fragments and non-peptidically bridged constructs. Finally, the previously postulated existence of a type II β-turn was confirmed with cyclic homodetic peptides. The 20-mer peptide was also fitted with photo labeling groups in order to elucidate the binding mode of this novel inhibitor to µ-calpain.