End-group functionalization of poly(2-oxazoline)s using methyl bromoacetate as initiator followed by direct amidation

Poly(2-alkyl/aryl-2-oxazoline)s (PAOx) are an alluring class of polymers for many applications due to the broad chemical diversity that is accessible for these polymers by simply changing the initiator, terminating agent and the monomer(s) used in their synthesis. Additional functionalities (that are not compatible with the cationic ring-opening polymerization) can be introduced to the polymers via orthogonal post-polymerization modifications. In this work, we expand this chemical diversity and demonstrate an easy and straightforward way to introduce a wide variety of functional end-groups to the PAOx, by making use of methyl bromoacetate (MeBrAc) as a functional initiator. A kinetic study for the polymerization of 2-ethyl-2-oxazoline (EtOx) in acetonitrile (CH3CN) at 140 degrees C revealed relatively slow initiation and slower polymerization than the commonly used initiator, methyl tosylate (MeOTs). Nonetheless, well-defined polymers could be obtained with MeBrAc as initiator, yielding polymers with near-quantitative methyl ester end-group functionality. Next, the post-polymerization modification of the methyl ester end-group with different amines was explored by introducing a range of functionalities, i.e. hydroxyl, amino, allyl and propargyl end-groups. The lower critical solution temperature (LCST) behavior of the resulting poly(2-ethyl-2-oxazoline)s was found to vary substantially in function of the end-group introduced, whereby the hydroxyl group resulted in a large reduction of the cloud point transition temperature of poly(2-ethyl-2-oxazoline), ascribed to hydrogen bonding with the polymer amide groups. In conclusion, this paper describes an easy and fast modular approach for the preparation of end-group functionalized PAOx

Maleimide end-functionalized poly(2-oxazoline)s by the functional initiator route : synthesis and (bio) conjugation

The synthesis of poly(2-ethyl-2-oxazoline)s with a maleimide group at the a chain end was carried out from new sultanate ester initiators bearing a furan-protected maleimide group. The conditions of the polymerization were optimized for 50 degrees 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 (D < 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 H-1 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

Maleimide end-functionalized poly(2-oxazoline)s by the functional initiator route: synthesis and (bio)conjugation

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 < Mn < 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

Systematic investigation of alkyl sulfonate initiators for the cationic ring-opening polymerization of 2-oxazolines revealing optimal combinations of monomers and initiators

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Formation of nanoporous materials via mild retro-Diels-Alder chemistry

Poly(styrene)-block-poly(ethylene oxide) copolymers synthesized via the combination of reversible addition fragmentation chain transfer (RAFT) polymerization and hetero Diels–Alder (HDA) cycloaddition can be cleaved in the solid state by a retro-HDA reaction occurring at 90 °C. Nanoporous films can be prepared from these polymers using a simple heating and washing procedure

Diels-Alder reactions as an efficient route to high purity cyclic polymers

A simple and efficient route for the synthesis of cyclic polymer systems is presented. Linear furan protected α-maleimide-ω-cyclopentadienyl functionalized precursors (poly(methyl methacrylate) and poly(tert-butyl acrylate)) were synthesized via atom transfer radical polymerization (ATRP) and subsequent substitution of the bromine end-group with cyclopentadiene. Upon heating at high dilution, deprotection of the dieneophile occurs followed by an intramolecular Diels–Alder reaction yielding a high purity cyclic product

Ambient temperature synthesis of triblock copolymers via orthogonal photochemically and thermally induced modular conjugation

A strategy for the modular ambient temperature synthesis of ABA and ABC triblock copolymers via a combination of photoinduced Diels-Alder reactions with thermal Diels-Alder reactions and azide-alkyne click chemistry is reported. Polystyrene (PS) and PMMA (PMMA) with α-2,5-dimethylbenzophenone and ω-cyclopentadienyl or ω-azide end-functionality were prepared via atom transfer radical polymerization (ATRP) and subsequent transformation of the bromine end-group. The phototriggered conjugation reaction proceeds via an in situ formation of highly reactive o-quinodimethanes. Maleimide-capped poly(tert-butyl acrylate) obtained via ATRP was employed as dienophile. Alkyne and maleimide functionalized poly(ethylene glycol) (PEG) were synthesized by esterification of monomethoxy PEG. PtBA-b-PMMA-b-PtBA and PtBA-b-PS-b-PtBA were successfully prepared in a one-pot reaction at ambient temperature combining photoinduced and thermal Diels-Alder reactions. ABC triblock copolymers (PtBA-b-PS-b-PEG) with narrow polydispersities were obtained via the combination of photoinduced Diels-Alder reactions with thermal Diels-Alder reactions as well as CuAAc chemistry. The polymers were characterized by size exclusion chromatography and 1H NMR spectroscopy. © 2011 American Chemical Society