Mathias Glassner | Ghent University (original) (raw)

Papers by Mathias Glassner

Poly(2-propyl-oxazoline)s can be prepared by living cationic ring-opening polymerization of 2-oxa... more Poly(2-propyl-oxazoline)s can be prepared by living cationic ring-opening polymerization of 2-oxazolines and represent an emerging class of biocompatible polymers exhibiting a lower critical solution temperature in aqueous solution close to body temperature. However, their usability is limited by the irre-versibility of the transition due to isothermal crystallization in case of poly(2-isopropyl-2-oxazoline) and the rather low glass transition temperatures (T g < 45 C) of poly(2-n-propyl-2-oxazoline)-based polymers. The copolymerization of 2-cyclopropyl-2-oxazoline and 2-ethyl-2-oxazoline presented herein yields gradient copolymers whose cloud point temperatures can be accurately tuned over a broad temperature range by simple variation of the composition. Surprisingly, all copolymers reveal lower T g s than the corresponding homopolymers ascribed to suppression of interchain interactions. However, it is noteworthy that the copolymers still have T g s > 45 C, enabling convenient storage in the fridge for future biomedical formulations.

A systematic kinetic investigation of the living cationic ring-opening polymerization (CROP) invo... more A systematic kinetic investigation of the living cationic ring-opening polymerization (CROP) involving 2-ethyl-2-oxazoline, 2-methyl-2-oxazoline, and 2-phenyl-2-oxazoline employing a series of alkyl sulfonate initiators with variation of the alkyl initiating fragment (methyl, ethyl, iso-propyl) and the leaving group/counterion (tosylate, nosylate, triflate) is reported. The study reveals that the initiation and propagation reactivity increases in the order tosylate < nosylate < triflate. Slow initiation is observed for EtOTs, while EtONs is a sufficiently fast initiator even for 2-phenyl-2-oxazoline. It is thus recommended to avoid the use of alkyl tosylates, except MeOTs, as initiators for the CROP of 2-alkyl-2-oxazolines. Although triflates are generally the best initiators, the use of the more stable and easier synthesizable nosylates provides a suitable alternative for the design of functional initiators for the CROP of 2-alkyl-2-oxazolines.

The surprising difference in the cationic ring-opening polymer-ization rate of 2-cyclopropyl-2-ox... more The surprising difference in the cationic ring-opening polymer-ization rate of 2-cyclopropyl-2-oxazoline versus 2-n-propyl-2-oxazoline and 2-isopropyl-2-oxazoline was investigated both experimentally and theoretically. The polymerization kinetics of all three oxazolines were experimentally measured in acetonitrile at 140 °C, and the polymerization rate constant (k p) was found to decrease in the order c-PropOx > n-PropOx > i-PropOx. Theoretical free energy calculations confirmed the trend for k p , and a set of DFT-based reactivity descriptors, electrostatics, and frontier molecular orbitals were studied to detect the factors controlling this peculiar behavior. Our results show that the observed reactivity is dictated by electrostatic effects. More in particular, the charge on the nitrogen atom of the monomer, used to measure its nucleophilicity, was the most negative for c-PropOx. Furthermore, the electrophilicity of the cations does not change substantially, and thus, the nucleophilicity of the monomers is the driving factor for k p .

Poly(2-oxazoline)s are a promising class of polymers for biomedical applications and a versatile ... more Poly(2-oxazoline)s are a promising class of polymers for biomedical applications and a versatile alternative to poly(ethylene glycol)s (PEG). In this work, the pharmacokinetic behavior of well defined 89 Zr-labeled poly(2-ethyl-2-oxazoline)s (PEtOx) was evaluated and compared to that of 89 Zr-labeled PEG, both with varying molar mass. Amine-terminated PEtOx of low dispersity in a molar mass range of 20 to 110 kDa and PEG of 20 and 40 kDa were functionalized with a desferrioxamine chelator and radiolabeled with 89 Zr. The tissue distribution of both radiolabeled PEtOx and PEG polymers was studied by means of micro Positron Emission Tomography (μPET) molecular imaging in mice longitudinally up to 1 week post injection, followed by ex vivo biodistribution. As previously described for other classes of non-ionic polymers, the blood clearance of PEtOx decreased with molar mass. The cut off for glomerular filtration of PEtOx is likely to be around 40 kDa. The head to head comparison of PEG and PEtOx revealed that the biodistribution is mostly dominated by polymer chain length and not polymer molar mass. This study constitutes an important addition to further establishing PEtOx as a promising polymer in biomedical applications.

The mechanochemical synthesis of a bicyclononyne tosylate (BCN-OTs) is presented. BCN-OTs is demo... more The mechanochemical synthesis of a bicyclononyne tosylate (BCN-OTs) is presented. BCN-OTs is demonstrated to be a good initiator for the cationic ring-opening polymerization of 2-ethyl-2-oxazoline directly yielding BCN functional poly(2-ethyl-2-oxazoline) (PEtOx-BCN) with high chain end fidelity. Subsequent strain-promoted cycloadditions of the resulting PEtOx-BCN enable efficient additive-free conjugation reactions as demonstrated for the formation of a block copolymer and a PEtOx-protein conjugate.

Poly(2-alkyl-2-oxazoline)s (PAOx) have received increasing interest for biomedical applications. ... more 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 biodis-tribution of poly(2-ethyl-2-oxazoline) (PEtOx) with a molar mass of 5 kDa radiolabeled with PET isotopes 89 Zr and 18 F. 18 F-labeled PEtOx is prepared by the strain-promoted azide−alkyne cycloaddition (SPAAC) of [ 18 F]fluoroethylazide to bicyclo[6.1.0]non-4-yne (BCN)-functionalized PEtOx as many common labeling strategies were found to be unsuccessful for PEtOx. 89 Zr-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 [ 18 F]-PEtOx displays a rapid and efficient clearance from the kidneys, 5 kDa [ 89 Zr]-Df-PEtOx is not efficiently cleared over the time course of the study, which is most likely caused by trapping of 89 Zr-labeled metabolites in the renal tubules and not the polymer itself, demonstrating the importance of selecting the appropriate label for biodistribution studies.

Journal of controlled release : official journal of the Controlled Release Society, Jan 10, 2016

Poly(2-oxazoline)s are a promising class of polymers for biomedical applications and a versatile ... more Poly(2-oxazoline)s are a promising class of polymers for biomedical applications and a versatile alternative to poly(ethylene glycol)s (PEG). In this work, the pharmacokinetic behavior of well defined (89)Zr-labeled poly(2-ethyl-2-oxazoline)s (PEtOx) was evaluated and compared to that of (89)Zr-labeled PEG, both with varying molar mass. Amine-terminated PEtOx of low dispersity in a molar mass range of 20 to 110kDa and PEG of 20 and 40kDa were functionalized with a desferrioxamine chelator and radiolabeled with (89)Zr. The tissue distribution of both radiolabeled PEtOx and PEG polymers was studied by means of micro Positron Emission Tomography (μPET) molecular imaging in mice longitudinally up to 1week post injection, followed by ex vivo biodistribution. As previously described for other classes of non-ionic polymers, the blood clearance of PEtOx decreased with molar mass. The cut off for glomerular filtration of PEtOx is likely to be around 40kDa. The head to head comparison of PEG ...

Macromolecules, Jun 28, 2011

A strategy for the modular ambient temperature synthesis of ABA and ABC triblock copolymers via a... more A strategy for the modular ambient temperature synthesis of ABA and ABC triblock copolymers via a combination of photoinduced DielsÀAlder reactions with thermal DielsÀAlder reactions and azideÀalkyne click chemistry is reported. Polystyrene (PS) and PMMA (PMMA) with R-2,5dimethylbenzophenone 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 DielsÀAlder reactions. ABC triblock copolymers (PtBA-b-PS-b-PEG) with narrow polydispersities were obtained via the combination of photoinduced DielsÀAlder reactions with thermal DielsÀAlder reactions as well as CuAAc chemistry. The polymers were characterized by size exclusion chromatography and 1 H NMR spectroscopy.

Journal of Polymer Science Part A: Polymer Chemistry, 2014

Angewandte Chemie, 2015

Das effiziente Abfangen photogenerierter Thioaldehyde durch funktionelle stabile Nitriloxide in e... more Das effiziente Abfangen photogenerierter Thioaldehyde durch funktionelle stabile Nitriloxide in einer 1,3dipolaren Cycloaddition ist eine neue und vielseitige photochemische Strategie zur Funktionalisierung von Polymeren und zur Oberflächenmodifikation unter milden und äquimolaren Bedingungen. Die modulare Ligation in Lçsung wird im Detail durch ESI-MS verfolgt. XPS wird zur Analyse der funktionalisierten Oberflächen verwendet, während ToF-SIMS die durch Anwendung einer Schattenmaske erreichte räumliche Kontrolle der Oberflächenfunktionalisierung belegt. Polymerbürsten wurden in einem räumlich begrenzten Bereich durch SI-ATRP von der Oberfläche aus wachsen gelassen, was mithilfe von ToF-SIMS, XPS sowie Ellipsometrie belegt wird.

Angewandte Chemie International Edition, 2015

The efficient trapping of photogenerated thioaldehydes with functional shelf-stable nitrile oxide... more The efficient trapping of photogenerated thioaldehydes with functional shelf-stable nitrile oxides in a 1,3-dipolar cycloaddition is a novel and versatile photochemical strategy for polymer end-group functionalization and surface modification under mild and equimolar conditions. The modular ligation in solution was followed in detail by electrospray ionization mass spectrometry (ESI-MS). X-ray photoelectron spectroscopy (XPS) was employed to analyze the functionalized surfaces, whereas time-of-flight secondary-ion mass spectrometry (ToF-SIMS) confirmed the spatial control of the surface functionalization using a micropatterned shadow mask. Polymer brushes were grown from the surface in a spatially confined regime by surface-initiated atom transfer radical polymerization (SI-ATRP) as confirmed by TOF-SIMS, XPS as well as ellipsometry.

ACS Macro Letters, 2013

The surprising difference in the cationic ring-opening polymerization rate of 2-cyclopropyl-2-oxa... more The surprising difference in the cationic ring-opening polymerization rate of 2-cyclopropyl-2-oxazoline versus 2-n-propyl-2-oxazoline and 2isopropyl-2-oxazoline was investigated both experimentally and theoretically. The polymerization kinetics of all three oxazolines were experimentally measured in acetonitrile at 140°C, and the polymerization rate constant (k p ) was found to decrease in the order c-PropOx > n-PropOx > i-PropOx. Theoretical free energy calculations confirmed the trend for k p , and a set of DFT-based reactivity descriptors, electrostatics, and frontier molecular orbitals were studied to detect the factors controlling this peculiar behavior. Our results show that the observed reactivity is dictated by electrostatic effects. More in particular, the charge on the nitrogen atom of the monomer, used to measure its nucleophilicity, was the most negative for c-PropOx. Furthermore, the electrophilicity of the cations does not change substantially, and thus, the nucleophilicity of the monomers is the driving factor for k p . P oly(2-oxazoline)s are synthetic polyamides that are regaining interest in the past decade because of their synthetic versatility in combination with an excellent biocompatibility. 1 The synthetic versatility results from their preparation via living cationic ring-opening polymerization (CROP), providing direct access to well-defined (co)polymers. 2 In addition, a wide range of monomers can be prepared and utilized in CROP to tune the polymer properties. 3 Poly(2-propyl-2-oxazoline) (poly(PropOx)) (co)polymers are of special interest due to their thermoresponsive phase transitions, i.e., lower critical solution temperature behavior, in aqueous solution. 4 We recently introduced poly(2-cyclopropyl-2-oxazoline) (poly(c-PropOx)) as an alternative for poly(2-isopropyl-2-oxazoline) (poly(i-PropOx)) and poly(2-n-propyl-2-oxazoline) (poly(n-PropOx)) (see Scheme 1 for monomer structures). It was demonstrated that poly(c-PropOx) has a higher glass transition temperature than poly(n-PropOx). Moreover, it is amorphous, preventing the irreversible crystallization upon thermal annealing as found for poly (i-PropOx). 5 This study surprisingly revealed that the CROP of c-PropOx was twice as fast as that of n-PropOx. Furthermore, Kataoka reported that n-PropOx is incorporated faster than i-PropOx during statistical copolymerizations, 4b although a direct comparison of homopolymerization rates has not been reported. Hence, it might be speculated that the reactivity for the CROP of PropOx decreases in the order c-PropOx > n-PropOx > i-PropOx.

European Polymer Journal, 2015

ABSTRACT A systematic kinetic investigation of the living cationic ring-opening polymerization (C... more ABSTRACT A systematic kinetic investigation of the living cationic ring-opening polymerization (CROP) involving 2-ethyl-2-oxazoline, 2-methyl-2-oxazoline, and 2-phenyl-2-oxazoline employing a series of alkyl sulfonate initiators with variation of the alkyl initiating fragment (methyl, ethyl, iso-propyl) and the leaving group/counterion (tosylate, nosylate, triflate) is reported. The study reveals that the initiation and propagation reactivity increases in the order tosylate &amp;lt; nosylate &amp;lt; triflate. Slow initiation is observed for EtOTs, while EtONs is a sufficiently fast initiator even for 2-phenyl-2-oxazoline. It is thus recommended to avoid the use of alkyl tosylates, except MeOTs, as initiators for the CROP of 2-alkyl-2-oxazolines. Although triflates are generally the best initiators, the use of the more stable and easier synthesizable nosylates provides a suitable alternative for the design of functional initiators for the CROP of 2-alkyl-2-oxazolines.

Macromolecules, 2011

A strategy for the modular ambient temperature synthesis of ABA and ABC triblock copolymers via a... more A strategy for the modular ambient temperature synthesis of ABA and ABC triblock copolymers via a combination of photoinduced DielsÀAlder reactions with thermal DielsÀAlder reactions and azideÀalkyne click chemistry is reported. Polystyrene (PS) and PMMA (PMMA) with R-2,5dimethylbenzophenone 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 DielsÀAlder reactions. ABC triblock copolymers (PtBA-b-PS-b-PEG) with narrow polydispersities were obtained via the combination of photoinduced DielsÀAlder reactions with thermal DielsÀAlder reactions as well as CuAAc chemistry. The polymers were characterized by size exclusion chromatography and 1 H NMR spectroscopy.

Macromolecular Rapid Communications, 2011

In the current contribution it is demonstrated -for the first time -that poly(ethylene) (M n ¼ 1 ... more In the current contribution it is demonstrated -for the first time -that poly(ethylene) (M n ¼ 1 400 as well as 2 800 g Á mol À1 , PDI ¼ 1.2) can be readily equipped with highly reactive cyclopentadienyl (Cp) end groups. The Cp terminal poly(ethylene) can subsequently be reacted in an efficient hetero Diels-Alder (HDA) reaction with macromolecules (poly(isobornyl acrylate) (M n ¼ 4 600 g Á mol À1 , PDI ¼ 1.10) and poly(styrene) (M n ¼ 6 300 g Á mol À1 , PDI ¼ 1.13) featuring strongly electron withdrawing thiocarbonyl thio end groups, prepared via reversible addition fragmentation chain transfer (RAFT) polymerization employing benzylpyridin-2-yldithioformate (BPDF) as transfer agent. The resulting block copolymers have been analyzed via high-temperature size exclusion chromatography (SEC) as well as nuclear magnetic resonance (NMR) spectroscopy. The current system allows for the removal of the excess of the nonpoly(ethylene) containing segment via filtration of the poly(ethylene)-containing block copolymer. However, the reaction temperatures need to be judiciously selected. Characterization of the generated block copolymers at elevated temperatures can lead -depending on the block copolymer type -to the occurrence of retro Diels-Alder processes. The present study thus demonstrates that RAFT-HDA ligation can be effectively employed for the generation of block copolymers containing poly(ethylene) segments.

Macromolecular Rapid Communications, 2011

Macromolecular Rapid Communications, 2011

Poly(2-propyl-oxazoline)s can be prepared by living cationic ring-opening polymerization of 2-oxa... more Poly(2-propyl-oxazoline)s can be prepared by living cationic ring-opening polymerization of 2-oxazolines and represent an emerging class of biocompatible polymers exhibiting a lower critical solution temperature in aqueous solution close to body temperature. However, their usability is limited by the irre-versibility of the transition due to isothermal crystallization in case of poly(2-isopropyl-2-oxazoline) and the rather low glass transition temperatures (T g < 45 C) of poly(2-n-propyl-2-oxazoline)-based polymers. The copolymerization of 2-cyclopropyl-2-oxazoline and 2-ethyl-2-oxazoline presented herein yields gradient copolymers whose cloud point temperatures can be accurately tuned over a broad temperature range by simple variation of the composition. Surprisingly, all copolymers reveal lower T g s than the corresponding homopolymers ascribed to suppression of interchain interactions. However, it is noteworthy that the copolymers still have T g s > 45 C, enabling convenient storage in the fridge for future biomedical formulations.

A systematic kinetic investigation of the living cationic ring-opening polymerization (CROP) invo... more A systematic kinetic investigation of the living cationic ring-opening polymerization (CROP) involving 2-ethyl-2-oxazoline, 2-methyl-2-oxazoline, and 2-phenyl-2-oxazoline employing a series of alkyl sulfonate initiators with variation of the alkyl initiating fragment (methyl, ethyl, iso-propyl) and the leaving group/counterion (tosylate, nosylate, triflate) is reported. The study reveals that the initiation and propagation reactivity increases in the order tosylate < nosylate < triflate. Slow initiation is observed for EtOTs, while EtONs is a sufficiently fast initiator even for 2-phenyl-2-oxazoline. It is thus recommended to avoid the use of alkyl tosylates, except MeOTs, as initiators for the CROP of 2-alkyl-2-oxazolines. Although triflates are generally the best initiators, the use of the more stable and easier synthesizable nosylates provides a suitable alternative for the design of functional initiators for the CROP of 2-alkyl-2-oxazolines.

The surprising difference in the cationic ring-opening polymer-ization rate of 2-cyclopropyl-2-ox... more The surprising difference in the cationic ring-opening polymer-ization rate of 2-cyclopropyl-2-oxazoline versus 2-n-propyl-2-oxazoline and 2-isopropyl-2-oxazoline was investigated both experimentally and theoretically. The polymerization kinetics of all three oxazolines were experimentally measured in acetonitrile at 140 °C, and the polymerization rate constant (k p) was found to decrease in the order c-PropOx > n-PropOx > i-PropOx. Theoretical free energy calculations confirmed the trend for k p , and a set of DFT-based reactivity descriptors, electrostatics, and frontier molecular orbitals were studied to detect the factors controlling this peculiar behavior. Our results show that the observed reactivity is dictated by electrostatic effects. More in particular, the charge on the nitrogen atom of the monomer, used to measure its nucleophilicity, was the most negative for c-PropOx. Furthermore, the electrophilicity of the cations does not change substantially, and thus, the nucleophilicity of the monomers is the driving factor for k p .

Poly(2-oxazoline)s are a promising class of polymers for biomedical applications and a versatile ... more Poly(2-oxazoline)s are a promising class of polymers for biomedical applications and a versatile alternative to poly(ethylene glycol)s (PEG). In this work, the pharmacokinetic behavior of well defined 89 Zr-labeled poly(2-ethyl-2-oxazoline)s (PEtOx) was evaluated and compared to that of 89 Zr-labeled PEG, both with varying molar mass. Amine-terminated PEtOx of low dispersity in a molar mass range of 20 to 110 kDa and PEG of 20 and 40 kDa were functionalized with a desferrioxamine chelator and radiolabeled with 89 Zr. The tissue distribution of both radiolabeled PEtOx and PEG polymers was studied by means of micro Positron Emission Tomography (μPET) molecular imaging in mice longitudinally up to 1 week post injection, followed by ex vivo biodistribution. As previously described for other classes of non-ionic polymers, the blood clearance of PEtOx decreased with molar mass. The cut off for glomerular filtration of PEtOx is likely to be around 40 kDa. The head to head comparison of PEG and PEtOx revealed that the biodistribution is mostly dominated by polymer chain length and not polymer molar mass. This study constitutes an important addition to further establishing PEtOx as a promising polymer in biomedical applications.

The mechanochemical synthesis of a bicyclononyne tosylate (BCN-OTs) is presented. BCN-OTs is demo... more The mechanochemical synthesis of a bicyclononyne tosylate (BCN-OTs) is presented. BCN-OTs is demonstrated to be a good initiator for the cationic ring-opening polymerization of 2-ethyl-2-oxazoline directly yielding BCN functional poly(2-ethyl-2-oxazoline) (PEtOx-BCN) with high chain end fidelity. Subsequent strain-promoted cycloadditions of the resulting PEtOx-BCN enable efficient additive-free conjugation reactions as demonstrated for the formation of a block copolymer and a PEtOx-protein conjugate.

Poly(2-alkyl-2-oxazoline)s (PAOx) have received increasing interest for biomedical applications. ... more 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 biodis-tribution of poly(2-ethyl-2-oxazoline) (PEtOx) with a molar mass of 5 kDa radiolabeled with PET isotopes 89 Zr and 18 F. 18 F-labeled PEtOx is prepared by the strain-promoted azide−alkyne cycloaddition (SPAAC) of [ 18 F]fluoroethylazide to bicyclo[6.1.0]non-4-yne (BCN)-functionalized PEtOx as many common labeling strategies were found to be unsuccessful for PEtOx. 89 Zr-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 [ 18 F]-PEtOx displays a rapid and efficient clearance from the kidneys, 5 kDa [ 89 Zr]-Df-PEtOx is not efficiently cleared over the time course of the study, which is most likely caused by trapping of 89 Zr-labeled metabolites in the renal tubules and not the polymer itself, demonstrating the importance of selecting the appropriate label for biodistribution studies.

Journal of controlled release : official journal of the Controlled Release Society, Jan 10, 2016

Poly(2-oxazoline)s are a promising class of polymers for biomedical applications and a versatile ... more Poly(2-oxazoline)s are a promising class of polymers for biomedical applications and a versatile alternative to poly(ethylene glycol)s (PEG). In this work, the pharmacokinetic behavior of well defined (89)Zr-labeled poly(2-ethyl-2-oxazoline)s (PEtOx) was evaluated and compared to that of (89)Zr-labeled PEG, both with varying molar mass. Amine-terminated PEtOx of low dispersity in a molar mass range of 20 to 110kDa and PEG of 20 and 40kDa were functionalized with a desferrioxamine chelator and radiolabeled with (89)Zr. The tissue distribution of both radiolabeled PEtOx and PEG polymers was studied by means of micro Positron Emission Tomography (μPET) molecular imaging in mice longitudinally up to 1week post injection, followed by ex vivo biodistribution. As previously described for other classes of non-ionic polymers, the blood clearance of PEtOx decreased with molar mass. The cut off for glomerular filtration of PEtOx is likely to be around 40kDa. The head to head comparison of PEG ...

Macromolecules, Jun 28, 2011

A strategy for the modular ambient temperature synthesis of ABA and ABC triblock copolymers via a... more A strategy for the modular ambient temperature synthesis of ABA and ABC triblock copolymers via a combination of photoinduced DielsÀAlder reactions with thermal DielsÀAlder reactions and azideÀalkyne click chemistry is reported. Polystyrene (PS) and PMMA (PMMA) with R-2,5dimethylbenzophenone 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 DielsÀAlder reactions. ABC triblock copolymers (PtBA-b-PS-b-PEG) with narrow polydispersities were obtained via the combination of photoinduced DielsÀAlder reactions with thermal DielsÀAlder reactions as well as CuAAc chemistry. The polymers were characterized by size exclusion chromatography and 1 H NMR spectroscopy.

Journal of Polymer Science Part A: Polymer Chemistry, 2014

Angewandte Chemie, 2015

Das effiziente Abfangen photogenerierter Thioaldehyde durch funktionelle stabile Nitriloxide in e... more Das effiziente Abfangen photogenerierter Thioaldehyde durch funktionelle stabile Nitriloxide in einer 1,3dipolaren Cycloaddition ist eine neue und vielseitige photochemische Strategie zur Funktionalisierung von Polymeren und zur Oberflächenmodifikation unter milden und äquimolaren Bedingungen. Die modulare Ligation in Lçsung wird im Detail durch ESI-MS verfolgt. XPS wird zur Analyse der funktionalisierten Oberflächen verwendet, während ToF-SIMS die durch Anwendung einer Schattenmaske erreichte räumliche Kontrolle der Oberflächenfunktionalisierung belegt. Polymerbürsten wurden in einem räumlich begrenzten Bereich durch SI-ATRP von der Oberfläche aus wachsen gelassen, was mithilfe von ToF-SIMS, XPS sowie Ellipsometrie belegt wird.

Angewandte Chemie International Edition, 2015

The efficient trapping of photogenerated thioaldehydes with functional shelf-stable nitrile oxide... more The efficient trapping of photogenerated thioaldehydes with functional shelf-stable nitrile oxides in a 1,3-dipolar cycloaddition is a novel and versatile photochemical strategy for polymer end-group functionalization and surface modification under mild and equimolar conditions. The modular ligation in solution was followed in detail by electrospray ionization mass spectrometry (ESI-MS). X-ray photoelectron spectroscopy (XPS) was employed to analyze the functionalized surfaces, whereas time-of-flight secondary-ion mass spectrometry (ToF-SIMS) confirmed the spatial control of the surface functionalization using a micropatterned shadow mask. Polymer brushes were grown from the surface in a spatially confined regime by surface-initiated atom transfer radical polymerization (SI-ATRP) as confirmed by TOF-SIMS, XPS as well as ellipsometry.

ACS Macro Letters, 2013

The surprising difference in the cationic ring-opening polymerization rate of 2-cyclopropyl-2-oxa... more The surprising difference in the cationic ring-opening polymerization rate of 2-cyclopropyl-2-oxazoline versus 2-n-propyl-2-oxazoline and 2isopropyl-2-oxazoline was investigated both experimentally and theoretically. The polymerization kinetics of all three oxazolines were experimentally measured in acetonitrile at 140°C, and the polymerization rate constant (k p ) was found to decrease in the order c-PropOx > n-PropOx > i-PropOx. Theoretical free energy calculations confirmed the trend for k p , and a set of DFT-based reactivity descriptors, electrostatics, and frontier molecular orbitals were studied to detect the factors controlling this peculiar behavior. Our results show that the observed reactivity is dictated by electrostatic effects. More in particular, the charge on the nitrogen atom of the monomer, used to measure its nucleophilicity, was the most negative for c-PropOx. Furthermore, the electrophilicity of the cations does not change substantially, and thus, the nucleophilicity of the monomers is the driving factor for k p . P oly(2-oxazoline)s are synthetic polyamides that are regaining interest in the past decade because of their synthetic versatility in combination with an excellent biocompatibility. 1 The synthetic versatility results from their preparation via living cationic ring-opening polymerization (CROP), providing direct access to well-defined (co)polymers. 2 In addition, a wide range of monomers can be prepared and utilized in CROP to tune the polymer properties. 3 Poly(2-propyl-2-oxazoline) (poly(PropOx)) (co)polymers are of special interest due to their thermoresponsive phase transitions, i.e., lower critical solution temperature behavior, in aqueous solution. 4 We recently introduced poly(2-cyclopropyl-2-oxazoline) (poly(c-PropOx)) as an alternative for poly(2-isopropyl-2-oxazoline) (poly(i-PropOx)) and poly(2-n-propyl-2-oxazoline) (poly(n-PropOx)) (see Scheme 1 for monomer structures). It was demonstrated that poly(c-PropOx) has a higher glass transition temperature than poly(n-PropOx). Moreover, it is amorphous, preventing the irreversible crystallization upon thermal annealing as found for poly (i-PropOx). 5 This study surprisingly revealed that the CROP of c-PropOx was twice as fast as that of n-PropOx. Furthermore, Kataoka reported that n-PropOx is incorporated faster than i-PropOx during statistical copolymerizations, 4b although a direct comparison of homopolymerization rates has not been reported. Hence, it might be speculated that the reactivity for the CROP of PropOx decreases in the order c-PropOx > n-PropOx > i-PropOx.

European Polymer Journal, 2015

ABSTRACT A systematic kinetic investigation of the living cationic ring-opening polymerization (C... more ABSTRACT A systematic kinetic investigation of the living cationic ring-opening polymerization (CROP) involving 2-ethyl-2-oxazoline, 2-methyl-2-oxazoline, and 2-phenyl-2-oxazoline employing a series of alkyl sulfonate initiators with variation of the alkyl initiating fragment (methyl, ethyl, iso-propyl) and the leaving group/counterion (tosylate, nosylate, triflate) is reported. The study reveals that the initiation and propagation reactivity increases in the order tosylate &amp;lt; nosylate &amp;lt; triflate. Slow initiation is observed for EtOTs, while EtONs is a sufficiently fast initiator even for 2-phenyl-2-oxazoline. It is thus recommended to avoid the use of alkyl tosylates, except MeOTs, as initiators for the CROP of 2-alkyl-2-oxazolines. Although triflates are generally the best initiators, the use of the more stable and easier synthesizable nosylates provides a suitable alternative for the design of functional initiators for the CROP of 2-alkyl-2-oxazolines.

Macromolecules, 2011

A strategy for the modular ambient temperature synthesis of ABA and ABC triblock copolymers via a... more A strategy for the modular ambient temperature synthesis of ABA and ABC triblock copolymers via a combination of photoinduced DielsÀAlder reactions with thermal DielsÀAlder reactions and azideÀalkyne click chemistry is reported. Polystyrene (PS) and PMMA (PMMA) with R-2,5dimethylbenzophenone 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 DielsÀAlder reactions. ABC triblock copolymers (PtBA-b-PS-b-PEG) with narrow polydispersities were obtained via the combination of photoinduced DielsÀAlder reactions with thermal DielsÀAlder reactions as well as CuAAc chemistry. The polymers were characterized by size exclusion chromatography and 1 H NMR spectroscopy.

Macromolecular Rapid Communications, 2011

In the current contribution it is demonstrated -for the first time -that poly(ethylene) (M n ¼ 1 ... more In the current contribution it is demonstrated -for the first time -that poly(ethylene) (M n ¼ 1 400 as well as 2 800 g Á mol À1 , PDI ¼ 1.2) can be readily equipped with highly reactive cyclopentadienyl (Cp) end groups. The Cp terminal poly(ethylene) can subsequently be reacted in an efficient hetero Diels-Alder (HDA) reaction with macromolecules (poly(isobornyl acrylate) (M n ¼ 4 600 g Á mol À1 , PDI ¼ 1.10) and poly(styrene) (M n ¼ 6 300 g Á mol À1 , PDI ¼ 1.13) featuring strongly electron withdrawing thiocarbonyl thio end groups, prepared via reversible addition fragmentation chain transfer (RAFT) polymerization employing benzylpyridin-2-yldithioformate (BPDF) as transfer agent. The resulting block copolymers have been analyzed via high-temperature size exclusion chromatography (SEC) as well as nuclear magnetic resonance (NMR) spectroscopy. The current system allows for the removal of the excess of the nonpoly(ethylene) containing segment via filtration of the poly(ethylene)-containing block copolymer. However, the reaction temperatures need to be judiciously selected. Characterization of the generated block copolymers at elevated temperatures can lead -depending on the block copolymer type -to the occurrence of retro Diels-Alder processes. The present study thus demonstrates that RAFT-HDA ligation can be effectively employed for the generation of block copolymers containing poly(ethylene) segments.

Macromolecular Rapid Communications, 2011

Macromolecular Rapid Communications, 2011