Tuning the LCST of poly(2‐cyclopropyl‐2‐oxazoline) via gradient copolymerization with 2‐ethyl‐2‐oxazoline

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 irreversibility 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_gs than the corresponding homopolymers ascribed to suppression of interchain interactions. However, it is noteworthy that the copolymers still have T_gs > 45 °C, enabling convenient storage in the fridge for future biomedical formulations. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 3118–3122     

Poly(cyclic imino ether)s Beyond 2‐Substituted‐2‐oxazolines

2‐Oxazolines (2‐OZO) are 5‐membered cyclic imino ethers whose cationic ring‐opening polymerization (CROP) mechanism and resulting polymer properties are extensively studied. However, also 6‐ and 7‐membered cyclic imino ethers can be polymerized via CROP. Together with the much less studied 4‐ and 5‐substituted main‐chain chiral poly(2‐oxazoline)s (P‐2‐OZO), these compounds are interesting monomers to enhance the versatility of (co)poly(cyclic imino ether)s. To emphasize the potential of such alternative cyclic imino ether monomers, we provide an overview on the polymerizations of 2‐oxazine (2‐OZI) and chiral 4‐ and 5‐substituted 2‐OZO as well as of selected properties of the resulting polymers. In addition, the hydrolysis of these polymers into the corresponding poly(alkylene imine)s will be addressed.

     

Design of new amphiphilic triblock copoly(2‐oxazoline)s containing a fluorinated segment

New amphiphilic triblock copoly(2‐oxazoline)s, containing hydrophobic domains with fluorine‐containing blocks, were synthesized. Using microwave radiation as heating source, triblock copolymers with narrow molar mass distributions were obtained by the sequential addition of 2‐ethyl‐2‐oxazoline, 2‐(1‐ethylheptyl)‐2‐oxazoline, and 2‐(2,6‐difluorophenyl)‐2‐oxazoline. The polymers obtained were characterized by size exclusion chromatography, ¹H NMR spectroscopy and matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (MALDI‐TOF MS). To investigate the incorporation of all three monomers into the triblock copolymers, a model polymer was prepared with shorter blocks exhibiting a suitable length to be measured in the reflector mode of a MALDI‐TOF MS. In addition, kinetic investigations on the homopolymerizations of all monomers were performed in nitromethane at 140 °C, yielding the polymerization rates under these conditions. DSC measurements of poly(2‐(1‐ethylheptyl)‐2‐oxazoline) and poly(2‐(2,6‐difluorophenyl)‐2‐oxazoline)) revealing glass transitions at about 33 and 120 °C, respectively. The thermal analysis of a blend of the two polymers showed two glass transitions revealing demixing, which could be an indicating for the immiscibility of the two components in the block copolymers. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010     

One‐pot synthesis of 2‐phenyl‐2‐oxazoline‐containing quasi‐diblock copoly(2‐oxazoline)s under microwave irradiation

The microwave‐assisted statistical copolymerization of 2‐phenyl‐2‐oxazoline with 2‐methyl‐2‐oxazoline or 2‐ethyl‐2‐oxazoline is discussed in this contribution. Kinetic studies of these statistical copolymerizations as well as reactivity ratio determinations were performed to investigate the monomer distribution in these copoly(2‐oxazoline)s, demonstrating the formation of quasi‐diblock copolymers. In addition, the synthesis of copolymer series with monomer concentrations ranging from 0 to 100 mol % is described. These copolymer series were characterized with ¹H NMR spectroscopy, gas chromatography, and gel permeation chromatography. Moreover, the glass‐transition temperatures and solubility of these copolymers were studied, and this revealing better mixing of poly(2‐methyl‐2‐oxazoline) (pMeOx) with poly(2‐phenyl‐2‐oxazoline) (pPhOx) than poly(2‐ethyl‐2‐oxazoline) (pEtOx) with poly(2‐phenyl‐2‐oxazoline) (pPhOx). © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 416–422, 2007.     

Synthesis and characterization of a series of diverse poly(2‐oxazoline)s

This article describes the synthesis and characterization of a variety of new poly(2‐oxazoline)s. With regard to functional polymers, 2‐oxazolines represent an interesting class of monomers because of the easy variation of the substituent in 2‐position. Starting from the corresponding nitriles, different 2‐oxazolines were obtained containing a diverse set of 2‐substituents, including thioether bonds ( M11 ), trifluoromethyl groups ( M8 , M10 ), and alkyl‐ or aryl groups ( M1 – M7 ). The subsequent polymerization of the majority of these monomers proceeded in a living manner, which was demonstrated by linear first‐order kinetics, a linear increase of molar mass with conversion, and relatively narrow molar mass distributions. In addition, selected thermal and surface properties of the polymers were studied utilizing DSC and contact‐angle measurements to determine the effects of different 2‐substituents on the macroscopic properties. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 3829–3838, 2009     

A Green Approach for the Synthesis and Thiol‐ene Modification of Alkene Functio1489lized Poly(2‐oxazoline)s

The bulk polymerization of 2‐(dec‐9‐enyl)‐2‐oxazoline ( DecEnOx ), a fatty acid‐based monomer for the cationic ring‐opening polymerization, is reported. Furthermore, under optimal conditions, namely microwave heating at 100 °C, the bulk copolymerization with 2‐ethyl‐2‐oxazoline yielded well‐defined copolymers. Due to its pendant alkene groups DecEnOx ‐based polymers possess the potential to be modified in efficient thiol‐ene reactions. The functionalization with thiols, e.g., dodecanethiol and 2,3,4,6‐tetra‐O‐acetyl‐1‐thio‐β‐D ‐glycopyranose in “green” solvents is demonstrated.

     

Synthesis of Poly(2‐oxazoline)‐Based Hydrogels with Tailor‐Made Swelling Degrees Capable of Stimuli‐Triggered Compound Release

A 32‐membered library of poly(2‐oxazoline)‐based hydrogels of the composition p EtOx _m‐p PhOx _n‐p PBO _q (m/n = 150/0, 100/50, 50/100, and 0/150; q = 1.5–30) was prepared from 2‐ethyl‐ ( EtOx ), 2‐phenyl‐2‐oxazoline ( PhOx ), and phenylene‐1,3‐bis‐(2‐oxazoline) ( PBO ). The polymerizations were performed from ground monomer mixtures at 140 °C in a single‐mode microwave reactor in reaction times as short as 1 h. Purified hydrogels, containing no residual monomers, were obtained in yields of 95% or higher. Acid‐mediated hydrolysis rates as well as swelling degrees of the hydrogels were adjustable over a broad range; swelling degrees in water/ethanol/dichloromethane ranged from 0 to 13.8/11.7/20.0. The hydrogels could incorporate organic molecules according to in situ or post‐synthetic routines. Post‐synthetic routines enabled for the preparation of hydrogels from which the incorporated compounds were only released through diffusion processes if the solvent was changed or through hydrogel degradation if the pH was lowered.     

Thermoresponsive polymeric nanoparticles based on poly(2‐oxazoline)s and tannic acid

Hydrogen bonding is widely present and plays a significant role in material science and supramolecular chemistry. This work reports a straightforward strategy for the preparation of polymeric nanoparticles from neutral poly(2‐oxazoline)s (POx) and tannic acid (TA) driven by their intermolecular hydrogen bonding. Dynamic light scattering (DLS) and scanning electron microscope (SEM) measurements showed that POx bearing different substituents, that is, methyl, ethyl and n‐propyl in the 2‐position all could assemble with TA into stable nanoparticles in water or ethanol. The diameter of the assembled nanoparticles could be manipulated by varying parameters such as molecular weight of POx, concentration and ratio of POx, and TA. Interestingly, POx/TA nanoparticles exhibited upper critical solution temperature (UCST)‐type thermoresponsive properties in ethanol or water depending on the molecular weight and substituent in the 2‐position of POx. Increasing or decreasing the temperature at the transition point resulted in the reversible transformation between assembled nanoparticles and disassembled poly(2‐n‐propyl‐2‐oxazoline) (PnPrOx) and TA. In view of the tailored size of the stable nanoparticles and the biocompatibilities of POx and TA, the prepared thermoresponsive nanoparticles are promising candidates as carriers for medicine toward related biomedical applications. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018 , 56, 1520–1527     

Multifunctional Poly(2‐oxazoline) Nanoparticles for Biological Applications

New multifunctional copoly(2‐oxazoline) nanoparticles were prepared for cell studies. The polymer contains double‐bond side chains as potential reaction sites for “thio”‐click reactions as well as a fluorescein label covalently bound to the polymer backbone. Using the nanoprecipitation technique, spherical nanoparticles of 200–800 nm were obtained. Confocal laser scanning microscopy measurements revealed the cellular uptake of the nanoparticles.

     

Microphase segregation and selective chain scission of poly(2‐methyl‐2‐oxazoline)‐block‐polystyrene

Herein, we report the design and synthesis of a block copolymer (BCP) with a high Flory–Huggins interaction parameter to access 10 nm feature sizes for potential lithographic applications. The investigated BCP is poly[(2‐methyl‐2‐oxazoline)‐block‐styrene] (PMeOx‐b‐PS), where the PMeOx segment functions as a hydrophilic segment. Two BCPs with different molecular weights were prepared using PMeOx as macroinitiator for copper(0) mediated controlled radical polymerization. The thin film self‐assembly of the obtained PMeOx‐b‐PS was performed by solvent annealing and investigated by atomic force microscopy. Both polymers formed PMeOx cylinders in a PS matrix with an average cylinder diameter of 10.5 nm. Additionally, the ability of the PMeOx domains to selectively degrade under ultraviolet irradiation was explored. It was shown that scission of the PMeOx block does occur selectively, and furthermore that the degraded domains can be removed while leaving the PS matrix intact. By combining synthetic accessibility, small feature sizes, and a selectively cleavable domain, this new BCP system holds significant promise as a lithographic mask for patterning surfaces with high precision. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 1349–1357     

Main‐chain chiral poly(2‐oxazoline)s: Influence of alkyl side‐chain on secondary structure formation in solution

The synthesis and microwave‐assisted polymerization of a series of chiral 2‐oxazolines with varying alkyl pendant groups, namely R‐2‐ethyl‐4‐ethyl‐2‐oxazoline (R‐EtEtOx), R‐2‐butyl‐4‐ethyl‐2‐oxazoline (R‐BuEtOx), R‐2‐octyl‐4‐ethyl‐2‐oxazoline, 2‐nonyl‐4‐ethyl‐2‐oxazoline, and R‐2‐undecyl‐4‐ethyl‐2‐oxazoline (R‐UndeEtOx), are reported. A kinetic investigation of the polymerization of R‐EtEtOx revealed a living polymerization mechanism. The poly(2‐oxazoline)s containing an ethyl, butyl, and octyl pendant group form similar chiral structures according to circular dichroism measurements. When the pendant group is further elongated, the chiral structure becomes more flexible in trifluoroethanol and the thermal response in hexafluoroisopropanol (HFIP) significantly changes. The short‐range structure of poly‐R‐BuEtOx dissolved in HFIP is thermoresponsive in a complex way, due to HFIP hydrogen bonding to the polymeric amide groups, whereas the long‐range structure determined from small angle neutron scattering is insensitive to temperature demonstrating that only the local secondary structure changes with temperature. In addition, the chiral structure of poly‐R‐UndeEtOx depends on the polarity of the solvent. The short‐range structure becomes more flexible in polar solvents, most likely due to interactions with the amide groups disturbing the secondary structure. In contrast, the long‐range structural transition from an ellipsoid in the apolar n‐hexane to a rod structure in the polar n‐butanol is ascribed to better solvation of the long aliphatic side chains. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Modification Pathways for Copoly(2‐oxazoline)s Enabling Their Application as Antireflective Coatings in Photolithography

Chromophore‐functionalized copoly(2‐oxazoline)s are successfully evaluated as bottom antireflective coatings (BARCs) in high‐resolution photolithography. With respect to UV light sources used in photolithographic production routines, anthracene is chosen as a chromophore. For application as polymer in BARCs, the copolymer poly(2‐ethyl‐2‐oxazolin)₄₅‐stat‐poly(2‐dec‐9′‐enyl‐2‐oxazolin)₂₀‐stat‐poly(2‐(3′‐(1″‐(anthracen‐9‐ylmethyl)‐1″,2″,3″‐triazol‐4‐yl)propyl)‐2‐oxazolin)₃₅ can be synthesized by the Huisgen cycloaddition click reaction of the copolymer poly(2‐ethyl‐2‐oxazolin)₄₅‐stat‐poly(2‐dec‐9′‐enyl‐2‐oxazolin)₂₀‐stat‐poly(2‐pent‐4′‐inyl‐2‐oxazolin)₃₅ and the corresponding azide‐functionalized anthracenes. These copolymers can be crosslinked by the thermally induced thiol‐ene reaction involving the unsaturated C=C bonds of the poly(2‐dec‐9′‐enyl‐2‐oxazoline) repetition units and a multifunctional thiol as crosslinker. Tests of this BARC in a clean room under production conditions reveal a significant decrease of the swing‐curve of a chemically amplified positive photoresist by more than 50%, hence significantly increasing the resolution of the photoresist.

     

Microwave Accelerated Polymerization of 2‐Phenyl‐2‐oxazoline

Summary: We studied the cationic ring‐opening polymerization of 2‐phenyl‐2‐oxazoline under microwave irradiation. A comparison with thermal heating shows a great enhancement in the reaction rates while the living character of the polymerization is conserved. The polymerizations were performed at the temperature of boiling butyronitrile (123 °C). The polymerization of 2‐phenyl‐2‐oxazoline under microwave conditions, described herein for the first time, is shown to be a rapid and environmentally friendly alternative to the classical methods.

Schematic of the activation of the reactive site by microwave irradiation.     

Multiple micellar morphologies from tri‐ and tetrablock copoly(2‐oxazoline)s in binary water–ethanol mixtures

We report on the micellization behavior of tri‐ and tetrablock copoly(2‐oxazoline)s in water–ethanol mixtures. The copolymers are based on different combinations of 2‐methyl‐, 2‐ethyl‐, 2‐phenyl‐, and 2‐nonyl‐2‐oxazoline. The solvophilic/solvophobic balance of these copolymers can be tuned thanks to the solubility dependence of the poly(2‐phenyl‐2‐oxazoline) block on the solvent composition. Characterization of the obtained micelles by dynamic light scattering and transmission electron microscopy revealed that their size and morphology depend on the solvophobic content of the copolymers and on the block order. Spherical micelles are always obtained when poly(2‐nonyl‐2‐oxazoline) is the only solvophobic block. When the solvophobic fraction consists of both the poly(2‐phenyl‐2‐oxazoline) and poly(2‐nonyl‐2‐oxazoline) blocks, spherical and cylindrical micelles as well as vesicles have been observed. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 3095–3102, 2010     

Synthesis,characterization, and cross‐linking of a library of statistical copolymers based on 2‐“soy alkyl”‐2‐oxazoline and 2‐ethyl‐2‐oxazoline

The synthesis of statistical copolymers consisting of 2‐ethyl‐2‐oxazoline (EtOx) and 2‐“soy alkyl”‐2‐oxazoline (SoyOx) via a microwave‐assisted cationic ring‐opening polymerization procedure is described. The majority of the resulting copolymers revealed polydispersity indices below 1.30. The reactivity ratios (r_EtOx 1.4 ± 0.3; r_SoyOx = 1.7 ± 0.3) revealed a clustered monomer distribution throughout the polymer chains. The thermal and surface properties of the pEtOx‐stat‐SoyOx copolymers were analyzed before and after UV‐curing demonstrating the decreased chain mobility after cross‐linking. In addition, the cross‐linked materials showed shape‐persistent swelling upon absorption of water from the air, whereby as little as 5 mol % SoyOx was found to provide efficient cross‐linking. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 5371,–5379, 2007     

Comparative studies on miscibility and phase behavior of linear and star poly(2‐methyl‐2‐oxazoline) blends with poly(vinylidene fluoride)

The comparative studies on the miscibility and phase behavior between the blends of linear and star‐shaped poly(2‐methyl‐2‐oxazoline) with poly(vinylidene fluoride) (PVDF) were carried out in this work. The linear poly(2‐methyl‐2‐oxazoline) was synthesized by the ring opening polymerization of 2‐methyl‐2‐oxazoline in the presence of methyl p‐toluenesulfonate (MeOTs) whereas the star‐shaped poly(2‐methyl‐2‐oxazoline) was synthesized with octa(3‐iodopropyl) polyhedral oligomeric silsesquioxane [(IC₃H₆)₈Si₈O₁₂, OipPOSS] as an octafunctional initiator. The polymers with different topological structures were characterized by means of Fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy. It is found that the star‐shaped poly(2‐methyl‐2‐oxazoline) was miscible with poly(vinylidene fluoride) (PVDF), which was evidenced by single glass‐transition temperature behavior and the equilibrium melting‐point depression. Nonetheless, the blends of linear poly(2‐methyl‐2‐oxazoline) with PVDF were phase‐separated. The difference in miscibility was ascribed to the topological effect of PMOx macromolecules on the miscibility. © 2006 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 44: 942–952, 2006     

Synthesis and properties of gradient copolymers based on 2‐phenyl‐2‐oxazoline and 2‐nonyl‐2‐oxazoline

In this study, the structure–property relationships for a series of statistical 2‐nonyl‐2‐oxazoline (NonOx) and 2‐phenyl‐2‐oxazoline (PhOx) copolymers were investigated for the first time. The copolymerization kinetics were studied and the reactivity ratios were calculated to be r_NonOx = 7.1 ± 1.4 and r_PhOx = 0.02 ± 0.1 revealing the formation of gradient copolymers. The synthesis of a systematical series of NonOx–PhOx copolymers is described, whereby the amount of NonOx was increased in steps of 10 mol %. The thermal and surface properties were investigated for this series of well‐defined copolymers. The thermal properties revealed a linear decrease in glass transition temperature for copolymers containing up to 39 wt % NonOx. Furthermore, the melting temperature of the copolymers containing 0 to 55 wt % PhOx linearly decreased most likely due to disturbance of the NonOx crystalline domains by incorporation of PhOx in the NonOx part of the copolymer. The surface energies of spincoated polymer films revealed a strong decrease in surface energy upon incorporation of NonOx in the copolymers due to strong phase separation between NonOx and PhOx allowing the NonOx chains to orient to the surface. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 6433–6440, 2009     

Synthesis of double hydrophilic poly(ethylene oxide)‐b‐poly(2‐hydroxyethyl acrylate) by single‐electron transfer–living radical polymerization

In this study, the polymerization of (2‐hydroxyethyl) acrylate (HEA), in polar media, using Cu(0)‐mediated radical polymerization also called single‐electron transfer–living radical polymerization (SET‐LRP) is reported. The kinetics aspects of both the homopolymerization and the copolymerization from a poly(ethylene oxide) (PEO) macroinitiator were analyzed by ¹H NMR. The effects of both the ligand and the solvent were studied. The polymerization was shown to reach very high monomer conversions and to proceed in a well‐controlled fashion in the presence of tris[2‐(dimethylamino)ethyl]amine Me6‐TREN and N, N,N′, N″, N″‐pentamethyldiethylenetriamine (PMDETA) in dimethylsulfoxide (DMSO). SET‐LRP of HEA was also led in water, and it was shown to be faster than in DMSO. In pure water, Me₆‐TREN allowed a better control over the molar masses and polydispersity indices than PMDETA and TREN. Double hydrophilic PEO‐b‐PHEA block copolymers, exhibiting various PHEA block lengths up to 100 HEA units, were synthesized, in the same manner, from a bromide‐terminated PEO macroinitiator. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Water‐Developable Poly(2‐oxazoline)‐Based Negative Photoresists

Copoly(2‐oxazoline)‐based photoresists are prepared from pEtOx₈₀Bu⁼Ox₂₀ and pPhOx₈₀Dc⁼Ox₂₀ , respectively, a tetrathiol, and a photosensitive initiator. It is possible to prepare copoly(2‐oxazoline)s bearing unsaturated side chains in a microwave reactor on a decagram scale in reaction times of 100 min or shorter. UV irradiation of dried polymer films through a quartz mask induces the thiol‐ene reaction in the illuminated areas. Subsequent development of the polymer films in halogen‐free solvents reproduces the negative pattern of the mask with a resolution of 2 μm. The pEtOx₈₀Bu⁼Ox₂₀ ‐derived photoresists can also be developed in water.     

Poly(2‐oxazoline) hydrogels crosslinked with aliphatic bis(2‐oxazoline)s: Properties,cytotoxicity, and cell cultivation

A series of hydrogels from 2‐ethyl‐2‐oxazoline and three bis(2‐oxazoline) crosslinkers—1,4‐butylene‐2,2′‐bis(2‐oxazoline), 1,6‐hexamethylene‐2,2′‐bis(2‐oxazoline), and 1,8‐octamethylene‐2,2′‐bis(2‐oxazoline)—are prepared. The hydrogels differ by the length of aliphatic chain of crosslinker and by the percentage of crosslinker (2–10%). The influence of the type and the percentage of the crosslinker on swelling properties, mechanical properties, and state of water is studied. The equilibrium swelling degree in water ranges from 2 to 20. With a proper selection of the crosslinker, Young's modulus can be varied from 10 kPa to almost 100 kPa. To evaluate the potential for medical applications, the cytotoxicity of extracts and the contact toxicity toward murine fibroblasts are measured. The hydrogels with the crosslinker containing a shorter aliphatic exhibit low toxicity toward fibroblast cells. Moreover, the viability and the proliferation of pancreatic β‐cells incubated inside hydrogels for 12 days are analyzed. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 1548–1559