End Capping Ring-Opening Olefin Metathesis Polymerization Polymers with Vinyl Lactones

The selective placement of a functional group at the chain end of a ring-opening metathesis polymer using ruthenium carbene initiators has been a significant limitation. Here we demonstrate a highly effective and facile end-capping technique for ROMP with living ruthenium carbene chain ends using single-turnover olefin metathesis substrates. Vinylene carbonate and 3H-furanone are introduced as functionalization and termination agents for the ruthenium-initiated ring-opening metathesis polymerization. This leads directly to the formation of functional polymer end groups without further chemical transformation steps. Aldehyde and carboxylic acid end groups can be introduced by this new method which involves the decomposition of acyl carbenes to ruthenium carbides. The high degrees of chain-end functionality obtained are supported by ^1H NMR spectroscopy, MALDI-ToF mass spectrometry, and end-group derivatization

Sacrificial Synthesis of Hydroxy-Functionalized ROMP Polymers: An Efficiency Study

We present here a ^1H NMR spectroscopy study of the kinetics of the ROMP macroinitiation of poly(exo-N-phenyl-2,3-norbornene dicarboximide) with various dioxepine derivatives and Grubbs first generation ruthenium initiators. We have recently demonstrated that this so-called “sacrificial block copolymer” approach yields hydroxy-functionalized ROMP polymers with high end-group functionality. This study shows that the substituents on the dioxepine are important for functionalization efficiency, in the order phenyl > isopropyl > methyl. Addition of triphenylphosphine to the ruthenium carbene initiator resulted in lower k_i/k_p (rate of initiation/rate of propagation) values for the macroinitiation than in the absence of triphenylphosphine. We demonstrate that the value of k_i/k_p for macroinitiations can be estimated for new sacrificial monomers by analyzing one or two functionalization reactions. This provides an easy tool for the rapid screening and evaluation of new sacrificial monomers

Sacrificial Synthesis of Hydroxy-Functionalized ROMP Polymers: An Efficiency Study

We present here a ^1H NMR spectroscopy study of the kinetics of the ROMP macroinitiation of poly(exo-N-phenyl-2,3-norbornene dicarboximide) with various dioxepine derivatives and Grubbs first generation ruthenium initiators. We have recently demonstrated that this so-called “sacrificial block copolymer” approach yields hydroxy-functionalized ROMP polymers with high end-group functionality. This study shows that the substituents on the dioxepine are important for functionalization efficiency, in the order phenyl > isopropyl > methyl. Addition of triphenylphosphine to the ruthenium carbene initiator resulted in lower k_i/k_p (rate of initiation/rate of propagation) values for the macroinitiation than in the absence of triphenylphosphine. We demonstrate that the value of k_i/k_p for macroinitiations can be estimated for new sacrificial monomers by analyzing one or two functionalization reactions. This provides an easy tool for the rapid screening and evaluation of new sacrificial monomers

Harnessing entropy to direct the bonding/debonding of polymer systems based on reversible chemistry

The widely accepted approach for controlling polymer debonding/rebonding properties in responsive materials has been to purposefully engineer the functional end-groups responsible for monomer dynamic bonding. Here, however, we evidence that the debondin

Exploiting the glioblastoma peptidome to discover novel tumour-associated antigens for immunotherapy

Peptides presented at the cell surface reflect the protein content of the cell; those on HLA class I molecules comprise the critical peptidome elements interacting with CD8 T lymphocytes. We hypothesize that peptidomes from ex vivo tumour samples encompass immunogenic tumour antigens. Here, we uncover >6000 HLA-bound peptides from HLA-A*02+ glioblastoma, of which over 3000 were restricted by HLA-A*02. We prioritized in-depth investigation of 10 glioblastoma-associated antigens based on high expression in tumours, very low or absent expression in healthy tissues, implication in gliomagenesis and immunogenicity. Patients with glioblastoma showed no T cell tolerance to these peptides. Moreover, we demonstrated specific lysis of tumour cells by patients' CD8+ T cells in vitro. In vivo, glioblastoma-specific CD8+ T cells were present at the tumour site. Overall, our data show the physiological relevance of the peptidome approach and provide a critical advance for designing a rational glioblastoma immunotherapy. The peptides identified in our study are currently being tested as a multipeptide vaccine (IMA950) in patients with glioblastom

New methods for the functionalization of metathesis polymers

Two general strategies for the functionalization of metathesis polymers are presented in this dissertation. Introducing Sacrificial Synthesis, many of the limitations of ruthenium-catalyzed ROMP have been overcome. Here, the living ROMP polymer to be functionalized was turned into a diblock copolymer by polymerizing dioxepine monomers onto the desired first polymer block. The second block was then later removed to leave “half-a-dioxepin”, i.e. exactly one hydroxyl group, at the chain-end. The efficiency of Sacrificial Synthesis is also studied. Thiol groups were also placed by a sacrificial strategy based on cyclic thioacetals. 2-Phenyl-1,3-dithiepin could be polymerized and subsequently cleaved by hydrogenation with Raney-Nickel. The presence of thiol groups on the chain end has been proven by chemical means (derivatization) and by coating gold-nanoparticles. The second strategy, vinyl lactone quenchingv is a termination reaction based on vinyl esters. After a metathesis step, an inactive Fischer-type carbene is formed. Such acyl carbenes are unstable and self-decompose to set an inactive ruthenium complex and the functional group free without changing the reaction conditions. The two compounds vinylene carbonate and 3H-furanone gave rise to the placement of aldehydes and carboxylic acids at the polymer chain ends without the necessity to perform any deprotection steps after the functionalization. The development of those two functionalization methods led to several applications. By reacting hydroxyl-functionalized ROMP-polymers with norbornene acid, macromonomers were formed which were subsequently polymerized to the respective graft-copolymers. Also, the derivatization of the same functionalized polymers with propargylic acid gave rise to alkyne-functionalized polymers which were conjugated with azides. Furthermore, “ugly stars”, i.e. long-chain branched structures were synthesized by polycondensation of ABn-type macromonomers and telechelic polymers were accessed combining the described functionalization techniques.Zwei generelle Synthesewege für endfunktionalisierte Metathesepolymere werden in dieser Dissertation vorgestellt. Durch die Einführung der „Sacrificial Synthesis“ konnten viele Limitationen der modernen Ruthenium-basierten ROMP überwunden werden. Hierbei wird dem lebenden Polymer das funktionalisiert werden soll ein weiteres, spaltbares Monomer zugesetzt, das bereits die funktionelle Gruppe versteckt trägt. Dieses zweite Monomer, ein cyclisches Acetal, wird dann in der Folge gespalten und hinterlässt quasi ein halbes Acetal, also eine Hydroxyl-Gruppe am Kettenende. Die Effizienz dieser Funktionalisierungsmethode wurde in einer Studie bestimmt. Thiole wurden ebenfalls über eine zerstörbare Monomereinheit, hier Thioacetalen, platziert. 2-Phenyl-1,3-dithiepin konnte polymerisiert und wiederum durch eine Hydrierung mit Raney Nickel gespalten werden. Die Anwesenheit einer Thiolgruppe am Kettenende konnte durch chemische Derivatisierung und durch die Beschichtung von Gold-Nanopartikeln gezeigt warden. Die zweite Strategie stellt eine klassische Terminierung, hier mit Viyllactonen, dar. Nach einem Metatheseschritt wird ein inaktives Fischer-Carben gebildet. Solche Acyl-Carbene sind instabil und zerfallen selbständig wobei eine weitere inaktive Ruthenium-Spezies und eine Funktionelle Gruppe freigesetzt werden ohne dass die Reaktionsbedingungen verändert werden müssen. Die beiden Terminierungsreagenzien Vinylencarbonat und 3H- Furanon ergeben ohne Entschützungsreaktionen Aldehyd- bzw. Carbonsäureendgruppen. Die Entwicklung dieser beiden Funktionalisierungsmethoden ermöglichte weiterhin die Anwendung in einigen Projekten. Durch die Veresterung der Hydroxylgruppen mit Norbornensäure konnten Makromonomere erhalten werden, die erfolgreich zu Kammpolymeren per ROMP polymerisiert wurden. Ebenso führte die Derivatisierung mit Propargylsäure zu Alkin-funktionalisierten Polymeren, die mit Aziden konjugiert wurden. Als weitere Projekte konnten statistisch langkettenverzweigte Polymere über ABn-Makromonomere erhalten, sowie Wege zur Bildung von Telechelen Polymeren durch Kombination der Methoden aufgezeigt werden

Current trends in the field of self-healing materials

The evolution of material design has mirrored advancements in the understanding of materials, nature, and the requirements of target applications. Originally, materials were only intended to play a passive role, but with a deepened understanding of material properties and design has come an improved ability to harness these properties to create materials with predetermined response mechanisms. This article has three aims: i) to briefly discuss the origin of and motivation for having materials that are capable of undergoing healing either extrinsically or intrinsically; ii) to present the most recent and promising advancements in the field of self-healing materials; and iii) to discuss important material design and property specifications that should be considered in order to promote the development of optimized self-healing materials. The development of self-healing materials has become of increasing interest to material scientists in the last 20 years, given the extraordinary advantages that such systems offer in a wide range of applications. The design of an optimal self-healing material depends on many factors, including material application, stability, and production cost. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim