Mathias Glassner

Owing to their outstanding mechanical, thermal, and chemical properties, polyoxazolidinones, which are accessible from the reaction of diepoxides and diisocyanates, have recently gained interest as a new class of high‐performance thermoplastic materials. However, mainly bisphenol A diglycidyl ether (BADGE) has thus far served as benchmark for the diepoxide part. Herein, ten bisphenol‐free diepoxides that are either bio‐based or derived from chemical recycling are presented. All these epoxides selectively resulted in linear polyoxazolidinones using methylene diphenyl diisocyanate (MDI) and p ‐tert‐butyl phenyl glycidyl ether as chain regulators. The new polymers were characterized, and the thermal and mechanical properties were compared to the BADGE‐based reference polyoxazolidinone. With three of the new diepoxide monomers, polyoxazolidinones with properties matching or surpassing those of BADGE‐based polyoxazolidinone were obtained.

Wir stellen die Biokonjugation von Polymeren vor, die durch RAFT‐Polymerisation mittels Hetero‐Diels‐Alder‐Cycloaddition durch ihren inhärenten terminalen Thiocarbonylthiorest mit einem dienmodifizierten Modellprotein synthetisiert wurden und keine spezifische funktionelle Endgruppe tragen. Die quantitative Konjugation erfolgt im Verlauf einiger Stunden bei Raumtemperatur und nahezu neutralem pH‐Wert und in Abwesenheit jeglichen Katalysators. Unsere Technologieplattform liefert thermoresponsive Biokonjugate, deren Aggregation allein durch die Polymerketten gesteuert wird.

We introduce the bioconjugation of polymers synthesized by RAFT polymerization, bearing no specific functional end group, by means of hetero‐Diels–Alder cycloaddition through their inherent terminal thiocarbonylthio moiety with a diene‐modified model protein. Quantitative conjugation occurs over the course of a few hours, at ambient temperature and neutral pH, and in the absence of any catalyst. Our technology platform affords thermoresponsive bioconjugates, whose aggregation is solely controlled by the polymer chains.

The effect of cubane side chains on polymer properties is rarely explored. Here, the synthesis of a 2-oxazoline monomer having a cubane moiety in the 2-position is reported. Cationic ring-opening polymerization gives the corresponding poly(2-oxazoline). However, homopolymerization only yields oligomeric species that were found to be insoluble in a wide range of solvents. Soluble polymers are obtained by copolymerization of the cubane containing monomer with 2-ethyl-2-oxazoline. The resulting copolymers show thermoresponsive behaviour in aqueous solution with a cloud point temperature that varies with copolymer composition. The methyl ester functionality of the cubane containing monomer can be used for side-chain modifications via a direct amidation post-polymerization modification reaction.

The synthesis of poly(2-ethyl-2-oxazoline)s with a maleimide group at the α chain end was carried out from new sulfonate ester initiators bearing a furan-protected maleimide group. The conditions of the polymerization were optimized for 50 °C using conventional heating (in contrast to microwave irradiation) to counteract the thermal lability of the cycloadduct introduced to protect the maleimide double bond. At this temperature, a tosylate variant was found to be unable to initiate the polymerization after several days. The controlled polymerization of 2-ethyl-2-oxazoline with a nosylate derivative was, however, successful as shown by kinetic experiments monitored by gas chromatography (GC) and size-exclusion chromatography (SEC). Poly(2-ethyl-oxazoline)s of various molar masses (4500 < M_n < 12 000 g mol⁻¹) with narrow dispersity (Đ < 1.2) were obtained. The stability of the protected maleimide functionality during the polymerization, its deprotection, and the reactivity of the deprotected end group by coupling with a model thiol molecule were proven by ¹H NMR spectroscopy and electrospray ionization mass spectrometry (ESI-MS). Finally, the conjugation of maleimide-functionalized poly(2-oxazoline) to a model protein (bovine serum albumin) was demonstrated by gel electrophoresis and MALDI-ToF mass spectrometry.

Poly(2‐oxazoline)s (PAOx) are of increasing importance for a wide range of applications, mostly in the biomedical field. This review describes the synthesis of 2‐oxazoline monomers and their cationic ring‐opening polymerization, and gives a comprehensive overview of all reported PAOx homopolymers. In the second part of the review, the polymer properties of these PAOx homopolymers with varying side‐chain structures are discussed. Altogether, this review intends to serve as an encyclopedia for poly(2‐oxazoline)s enabling the straightforward selection of a polymer structure with the desired properties for a certain application. © 2017 Society of Chemical Industry

Poly(2-alkyl-2-oxazoline)s (PAOx) have received increasing interest for biomedical applications. Therefore, it is of fundamental importance to gain an in-depth understanding of the biodistribution profile of PAOx. We report the biodistribution of poly(2-ethyl-2-oxazoline) (PEtOx) with a molar mass of 5 kDa radiolabeled with PET isotopes ⁸⁹Zr and ¹⁸F. ¹⁸F-labeled PEtOx is prepared by the strain-promoted azide–alkyne cycloaddition (SPAAC) of [¹⁸F]fluoroethylazide to bicyclo[6.1.0]non-4-yne (BCN)-functionalized PEtOx as many common labeling strategies were found to be unsuccessful for PEtOx. ⁸⁹Zr-labeled PEtOx is prepared using desferrioxamine end-groups as a chelator. Five kDa PEtOx shows a significantly faster blood clearance compared to PEtOx of higher molar mass while uptake in the liver is lower, indicating a minor contribution of the liver in excretion of the 5 kDa PEtOx. While [¹⁸F]-PEtOx displays a rapid and efficient clearance from the kidneys, 5 kDa [⁸⁹Zr]-Df-PEtOx is not efficiently cleared over the time course of the study, which is most likely caused by trapping of ⁸⁹Zr-labeled metabolites in the renal tubules and not the polymer itself, demonstrating the importance of selecting the appropriate label for biodistribution studies.

The mechanochemical synthesis of a bicyclononyne tosylate (BCN-OTs) and its subsequent use for the CROP of 2-ethyl-2-oxazoline yielding bioorthogonal clickable poly(2-ethyl-2-oxazoline) is presented.