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Ion mobility-mass spectrometry (IM-MS) experiments are mostly used hand in hand with computational chemistry to correlate mobility measurements to the shape of the ions. Recently, we developed an automatable method to fit IM data obtained with synthetic homopolymers (i.e., collision cross sections; CCS) without resorting to computational chemistry. Here, we further develop the experimental IM data interpretation to explore physicochemical properties of a series of nine polymers and their monomer units by monitoring the relationship between the CCS and the degree of polymerization (DP). Several remarkable points of the CCS evolutions as a function of the DP were found: the first observed DP of each charge state (ΔDPfirst DP), the DPs constituting the structural rearrangements (ΔDPrearr), and the DPs at the half-rearrangement (DPhalf-rearr). Given that these remarkable points do not rely on absolute CCS values, but on their relative evolution, they can be extracted from CCS or raw IM data without accurate IM calibration. Properties such as coordination numbers of the cations, steric hindrance, or side chain flexibility can be compared. This leads to fit parameter predictions based on the nature of the monomer unit. The interpretation of the fit parameters, extracted using solely experimental data, allows a rapid screening of the properties of the polymers.

Poly(2-ethyl-2-oxazoline) (PEtOx) is the most common poly(2-oxazoline) for biomedical applications resulting from its high water-solubility, good commercial availability and well-controlled polymerization. In this article, we report the polymerization of 2-ethyl-2-oxazoline (EtOx) in ethyl acetate to replace the current state-of-the-art polymerization of EtOx in acetonitrile and chlorobenzene. This switch towards ethyl acetate as green solvent is an important improvement towards pharmaceutical compliance/compatibility, besides the lower burden for the environment.

When polymer mixtures become increasingly complex, the conventional analysis techniques become insufficient for complete characterization. Mass spectrometric techniques can satisfy this increasing demand for detailed sample characterization. Even though isobaric polymers are indistinguishable using simple mass spectrometry (MS) analyses, more advanced techniques such as tandem MS (MS/MS) or ion mobility (IM) can be used. Here, we report proof of concept for characterizing isomeric polymers, namely poly(2-n-propyl-2-oxazoline) (Pn-PrOx) and poly(2-isopropyl-2-oxazoline) (Pi-PrOx), using MS/MS and IM-MS. Pi-PrOx ions lose in intensity at higher accelerating voltages than Pn-PrOx ions during collision-induced dissociation (CID) MS/MS experiments. A Pn/i-PrOx mixture could also be titrated using survival yield calculations of either precursor ions or cation ejection species. IM-MS yielded shape differences in the degree of polymerization (DP) regions showing the structural rearrangements. Combined MS techniques are thus able to identify and deconvolute the molar mass distributions of the two isomers in a mixture. Finally, the MS/MS and IM-MS behaviors are compared for interpretation. Graphical Abstract .

Enzymatically degradable polymeric micelles have great potential as drug delivery systems, allowing the selective release of their active cargo at the site of disease. Furthermore, enzymatic degradation of the polymeric nanocarriers facilitates clearance of the delivery system after it has completed its task. While extensive research is dedicated toward the design and study of the enzymatically degradable hydrophobic block, there is limited understanding on how the hydrophilic shell of the micelle can affect the properties of such enzymatically degradable micelles. In this work, we report a systematic head-To-head comparison of well-defined polymeric micelles with different polymeric shells and two types of enzymatically degradable hydrophobic cores. To carry out this direct comparison, we developed a highly modular approach for preparing clickable, spectrally active enzyme-responsive dendrons with adjustable degree of hydrophobicity. The dendrons were linked with three different widely used hydrophilic polymers-poly(ethylene glycol), poly(2-ethyl-2-oxazoline), and poly(acrylic acid) using the CuAAC click reaction. The high modularity and molecular precision of the synthetic methodology enabled us to easily prepare well-defined amphiphiles that differ either in their hydrophilic block composition or in their hydrophobic dendron. The micelles of the different amphiphiles were thoroughly characterized and their sizes, critical micelle concentrations, drug loading, stability, and cell internalization were compared. We found that the micelle diameter was almost solely dependent on the hydrophobicity of the dendritic hydrophobic block, whereas the enzymatic degradation rate was strongly dependent on the composition of both blocks. Drug encapsulation capacity was very sensitive to the type of the hydrophilic block, indicating that, in addition to the hydrophobic core, the micellar shell also has a significant role in drug encapsulation. Incubation of the spectrally active micelles in the presence of cells showed that the hydrophilic shell significantly affects the micellar stability, localization, cell internalization kinetics, and the cargo release mechanism. Overall, the high molecular precision and the ability of these amphiphiles to report their disassembly, even in complex biological media, allowed us to directly compare the different types of micelles, providing striking insights into how the composition of the micelle shells and cores can affect their properties and potential to serve as nanocarriers.

Polymer solutions with a lower critical solution temperature (LCST) undergo reversible phase separation when heated above their cloud point temperature (T-CP or CPT). As such, they have been proposed for a wide range of biomedical applications, from injectable drug depots to switchable coatings for cell adhesion. However, in systematic studies, the T-CP of these thermoresponsive polymers has been mostly measured in non-physiological solutions, thereby hindering the development of their medicinal applications. Here, we analysed the thermoresponsive properties of four acrylamide-based polymers with LCST, namely poly[(N-2,2-difluoroethyl)acrylamide] (pDFEA), poly[(N-isopropyl)acrylamide] (pNIPAM), poly[(N,N-diethyl)acrylamide] (pDEA), and poly[(N-acryloyl)pyrrolidine] (pAP). As shown by turbidimetty, their T-CP in phosphate saline buffer (PBS) and foetal bovine serum (FBS) were consistently lower than those reported in the literature, typically assessed in pure water, even when using the same setup. in addition, these physiological solutions affected the variation of T-CP as a function of polymer concentration (1.25 to 10.0 mg mL(-)(1)) and molar mass (20 to 50 kg mol(-1)). As shown by isothermal calorimetry, interactions between proteins in FBS and polymer aggregates were predominantly exothermic, which indicates that protein polymer complexes are formed through enthalpically driven processes. in conclusion, the T-CP of thermoresponsive polymers strongly depends on solvent composition and therefore should be measured under physiological conditions for future medicinal applications.

Temperature-responsive nanomaterials have gained increasing interest over the past decade due their ability to undergo conformational changes in situ, in response to a change in temperature. One class of temperature-responsive polymers are those with lower critical solution temperature, which phase separate in aqueous solution above a critical temperature. When these temperature-responsive polymers are grafted to a solid nanoparticle, a change in their surface properties occurs above this critical temperature, from hydrophilic to more hydrophobic, giving them a propensity to aggregate. This study explores the temperature induced aggregation of silica nanoparticles functionalised with two isomeric temperature-responsive polymers with lower critical solution temperature (LCST) behavior, namely poly(N-isopropyl acrylamide) (PNIPAM), and poly(2-n-propyl-2-oxazoline) (PNPOZ) with similar molecular weights (5000 Da) and grafting density. These nanoparticles exhibited striking differences in the temperature of aggregation, which is consistent with LCST of each polymer. Using a combination of small-angle neutron scattering (SANS) and dynamic light scattering (DLS), we probed subtle differences in the aggregation mechanism for PNIPAM- and PNPOZ-decorated silica nanoparticles. The nanoparticles decorated with PNIPAM and PNPOZ show similar aggregation mechanism that was independent of polymer structure, whereby aggregation starts by the formation of small aggregates. A further increase in temperature leads to interaction between these aggregates and results in full-scale aggregation and subsequent phase separation.

New functional initiators for the cationic ring-opening polymerization of 2-alkyl-2-oxazolines are described to introduce a thiol moiety at the alpha terminus. Both tosylate and nosylate initiators carrying a thioacetate group are obtained in multigram scale, from commercial reagents in two steps, including a phototriggered thiol-ene radical addition. The nosylate derivative gives access to a satisfying control over the cationic ring-opening polymerization of 2-ethyl-2-oxazoline, with dispersity values lower than 1.1 during the entire course of the polymerization, until full conversion. Cleavage of the thioacetate end group is rapidly achieved using triazabicyclodecene, thereby leading to a mercapto terminus. The latter gives access to a new subgeneration of alpha-functional poly(2-oxazoline)s (butyl ester,N-hydroxysuccinimidyl ester, furan) by Michael addition with commercial (meth)acrylates. The amenability of the mercapto-poly(2-ethyl-2-oxazoline) for covalent surface patterning onto acrylated surfaces is demonstrated in a microchannel cantilever spotting (mu CS) experiment, characterized by X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary-ion mass spectrometry (ToF-SIMS).

Buckminsterfullerene (C-60) has a large potential for biomedical applications. However, the main challenge for the realization of its biomedical application potential is to overcome its extremely low water solubility. One approach is the coformulation with biocompatible water-soluble polymers, such as poly(2-oxazoline)s (PAOx), to form water-soluble C-60 nanoparticles (NPs). However, uniform and defined NPs have only been obtained via a thin film hydration method or using cyclodextrin-functionalized PAOx. Here, we report the mechanochemical preparation of defined and stable C-60:PAOx NPs by the introduction of a simple alkyne group as a polymer end-group. The presence of this alkyne bond is proven to be crucial in the mechanochemical synthesis of stable, defined sub-100 nm C-60:PAOx NPs, with high C-60 content up to 8.9 wt %.

Polymer characterizations are often performed using mass spectrometry (MS). Aside from MS and different tandem MS (MS/MS) techniques, ion mobility–mass spectrometry (IM-MS) has been recently added to the inventory of characterization technique. However, only few studies have focused on the reproducibility and robustness of polymer IM-MS analyses. Here, we perform collisional and electron-mediated activation of polymer ions before measuring IM drift times, collision cross-sections (CCS), or reduced ion mobilities (K0). The resulting IM behavior of different activated product ions is then compared to non-activated native intact polymer ions. First, we analyzed collision induced unfolding (CIU) of precursor ions to test the robustness of polymer ion shapes. Then, we focused on fragmentation product ions to test for shape retentions from the precursor ions: cation ejection species (CES) and product ions with m/z and charge state values identical to native intact polymer ions. The CES species are formed using both collision induced dissociation (CID) and electron transfer dissociation (ETD, formally ETnoD) experiments. Only small drift time, CCS, or K0 deviations between the activated/formed ions are observed compared to the native intact polymer ions. The polymer ion shapes seem to depend solely on their mass and charge state. The experiments were performed on three synthetic homopolymers: poly(ethoxy phosphate) (PEtP), poly(2-n-propyl-2-oxazoline) (Pn-PrOx), and poly(ethylene oxide) (PEO). These results confirm the robustness of polymer ion CCSs for IM calibration, especially singly charged polymer ions. The results are also discussed in the context of polymer analyses, CCS predictions, and probing ion–drift gas interaction potentials.

Water-soluble polymers are still the most popular carrier for the preparation of amorphous solid dispersions (ASDs). The advantage of this type of carrier is the fast drug release upon dissolution of the water-soluble polymer and thus the initial high degree of supersaturation of the poorly soluble drug. Nevertheless, the risk for precipitation due to fast drug release is a phenomenon that is frequently observed. In this work, we present an alternative carrier system for ASDs where a water-soluble and water-insoluble carrier are combined to delay the drug release and thus prevent this onset of precipitation. Poly(2-alkyl-2-oxazoline)s were selected as a polymer platform since the solution properties of this polymer class depend on the length of the alkyl sidechain. Poly(2-ethyl-2-oxazoline) (PEtOx) behaves as a water-soluble polymer at body temperature, while poly(2-n-propyl-2-oxazoline) (PPrOx) and poly(2-sec-butyl-2-oxazoline) (PsecBuOx) are insoluble at body temperature. Since little was known about the polymer&rsquo, s miscibility behaviour and especially on how the presence of a poorly-water soluble drug impacted their miscibility, a preformulation study was performed. Formulations were investigated with X-ray powder diffraction, differential scanning calorimetry (DSC) and solid-state nuclear magnetic resonance spectroscopy. PEtOx/PPrOx appeared to form an immiscible blend based on DSC and this was even more pronounced after heating. The six drugs that were tested in this work did not show any preference for one of the two phases. PEtOx/PsecBuOx on the other hand appeared to be miscible forming a homogeneous blend between the two polymers and the drugs.

Despite the fact that solid dispersions are gaining momentum, the number of polymers that have been used as a carrier during the past 50 years is rather limited. Recently, the poly(2-alkyl-2-oxazoline) (PAOx) polymer class profiled itself as a versatile platform for a wide variety of applications in drug delivery, including their use as amorphous solid dispersion (ASD) carrier. The aim of this study was to investigate the potential of poly(2-ethyl-2-oxazoline) (PEtOx) by applying a benchmark approach with well-known, commercially available carriers (i.e. polyvinylpyrrolidone (PVP) K30, poly(vinylpyrrolidone-co-vinyl acetate) (PVP-VA) 64 and hydroxypropylmethylcellulose (HPMC)). For this purpose, itraconazole (ITC) and fenofibrate (FFB) were selected as poorly water-soluble model drugs. The four polymers were compared by establishing their supersaturation maintaining potential and by investigating their capability as carrier for ASDs with high drug loadings. Spray drying, as well as hot melt extrusion and cryo-milling were implemented as ASD manufacturing technologies for comparative evaluation. For each manufacturing technique, the formulations with the highest possible drug loadings were tested with respect to in vitro drug release kinetics. This study indicates that PEtOx is able to maintain supersaturation of the drugs to a similar extent as the commercially available polymers and that ASDs with comparable drug loadings can be manufactured. The results of the in vitro dissolution tests reveal that high drug release can be obtained for PEtOx formulations. Overall, proof-of-concept is provided for the potential of PEtOx for drug formulation purposes. ispartof: EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS vol:144 pages:79-90 ispartof: location:Netherlands status: published

Block copolymer micelles hold great promise for developing next generation drug delivery vehicles to improve therapeutics. In this work, the biocompatibility of poly(2-alkyl-2-oxazoline)s (PAOx) was combined with the biodegradability and biocompatibility of aliphatic polycarbonates through the preparation of block copolymers. These well-defined blocks were prepared via cationic ring-opening polymerisation (CROP) of 2-oxazolines followed by the organocatalytic ring-opening polymerisation (ROP) of cyclic carbonate monomers. The improved synthesis of hydroxyl terminated poly(2-ethyl-2-oxazoline)s (PEtOx-OH) is reported allowing high end-group fidelity. These polymers were used as macroinitiators in the controlled ROP of various cyclic carbonate monomers (TMC and benzyl, allyl, propargyl, bromide and morpholino functional monomers) resulting in well-defined amphiphilic block copolymers.

There is an increasing need for smart materials capable of removing multivalent ions from aqueous streams without the inconvenience of brine regeneration as in ion-exchange processes. Herein, we present a thermoresponsive micellar system consisting of polystyrene-poly(methoxy diethyleneglycol acrylate) block copolymer surfactants modified with carboxylic acid end groups (PS-PMDEGA-COOH) that can be used to switch between the adsorption and desorption of divalent calcium(II) cations by a mild temperature trigger, thus providing a new type of thermoregenerable ion-adsorbing materials. The switch of calcium(II)-binding capacity is demonstrated to result from a shift in the pKa value of the carboxylic acid groups by the collapse and redissolution of the PMDEGA block and the associated change in local polarity.

A straightforward end-capping strategy is applied to synthesize xanthate-functional poly(2-alkyl-2-oxazoline)s (PAOx) that enable gold nanoparticle functionalization by a direct "grafting to" approach with citrate-stabilized gold nanoparticles (AuNPs). Owing to the presence of remaining citrate groups, the obtained PAOx@AuNPs exhibit dual stabilization by repulsive electrostatic and steric interactions giving access to water soluble molecular AND logic gates, wherein environmental temperature and ionic strength constitute the input signals, and the solution color the output signal. The temperature input value could be tuned by variation of the PAOx polymer composition, from 22 degrees C for poly(2-(n)propyl-2-oxazoline)@AuNPs to 85 degrees C for poly(2-ethyl-2-oxazoline)@AuNPs. Besides, advancing the fascinating field of molecular logic gates, the present research offers a facile strategy for the synthesis of PAOx@AuNPs of interest in fields spanning nanotechnology and biomedical sciences. In addition, the functionalization of PAOx with xanthate offers straightforward access to thiol-functional PAOx of high interest in polymer science.

A poly[(2-ethyl-2-oxazoline)-ran-(2-nonyl-2-oxazoline)] random copolymer was synthesized and its thermoresponsive behavior in aqueous solution modulated by the addition of different supramolecular host molecules. The macrocycles formed inclusion complexes with the nonyl aliphatic side-chains present in the copolymer, increasing its cloud point temperature. The extent of this temperature shift was found to depend on the cavitand concentration and on the strength of the host-guest complexation. The cloud point temperature could be tuned in an unprecedented wide range of 30 K by supramolecular interactions. Since the temperature-induced breakage of the inclusion complexes constitutes the driving force for the copolymer phase transition, the shift in cloud point temperature could be utilized to estimate the association constant of the nonyl side chains with the cavitands.

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.

Buckminster fullerene (C60 )'s main hurdle to enter the field of biomedicine is its low bioavailability, which results from its extremely low water solubility. A well-known approach to increase the water solubility of C60 is by complexation with γ-cyclodextrins. However, the formed complexes are not stable in time as they rapidly aggregate and eventually precipitate due to attractive intermolecular forces, a common problem in inclusion complexes of cyclodextrins. In this study we attempt to overcome the attractive intermolecular forces between the complexes by designing custom γ-cyclodextrin (γCD)-based supramolecular hosts for C60 that inhibit the aggregation found in native γCD-C60 complexes. The approach entails the introduction of either repulsive electrostatic forces or increased steric hindrance to prevent aggregation, thus enhancing the biomedical application potential of C60 . These modifications have led to new sub-100 nm nanostructures that show long-term stability in solution.

A poly[(2-ethyl-2-oxazoline)-ran-(2-nonyl-2-oxazoline)] copolymer in combination with hydroxypropylated cyclodextrins has been demonstrated to lead to a supramolecular self-assembly process that results in the formation of kinetically trapped thermoresponsive nanoparticles. Selection of the cyclodextrin type provides control over the nanoparticle phase-transition thermodynamics, thus affording optical temperature sensors with an unprecedented, long-term thermal memory function, which is reversible or irreversible. This research also sheds light onto kinetic and dynamic supramolecular assemblies, thus providing important insight because similar supramolecular processes are at the foundation of living matter.

Poly(2-propyl-oxazoline)s can be prepared by living cationic ring-opening polymerization of 2-oxazolines and repre- sent 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 (Tg 45 C, enabling convenient storage in the fridge for future biomedical formulations. V C 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014, 00, 000-000

Poly(2-oxazoline)s (in literature abbreviated as PAOx, POx, or POZ, herein referred to as PAOx) represent an emerging class of biocompatible polymers outperforming polyethylene glycol (PEG) in many aspects, including their high synthetic versatility and structural modularity. In this review, we provide a brief introduction to PAOx chemistry and biology to sketch their potential in biomaterials science. Further, we provide a detailed comprehensive overview of the literature on PAOx-protein conjugates with emphasis on their critical evaluation and comparison with analogous systems based on PEG. Based on this literature overview, PAOx seem to be an excellent alternative to PEG in the construction of therapeutic polymer-protein conjugates.

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 °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.

D.D.C.B. thanks the University of Oxford for startup funds including a research fellowship for S.N.

The modification of solid surfaces with supramolecular hosts is a powerful method to tailor interfacial properties and confer chemical selectivity, but often involves multistep protocols that hinder facile upscaling. Here, we demonstrate the one-step covalent modification of highly oriented pyrolytic graphite (HOPG) with a β-cyclodextrin (β-CD) derivative, which efficiently forms inclusion complexes with hydrophobic guests of suitable size (e.g. ferrocene, dopamine). The modified β-CD-HOPG electrode discriminates analytes that form host-guest complexes with β-CD against a 100-fold higher background of electroactive substances that do not, even when these possess similar redox potentials. In addition, the enrichment of the analytes at the electrode surface, through complex formation with the β-CD units, leads to an enhanced electrochemical response and an improved detection limit (one order of magnitude for dopamine, compared to current cyclodextrin-based sensors). The two unique features we demonstrate for the covalently grafted β-CD-HOPG electrode (selective sensing of hydrophobic analytes and ultrasensitive dopamine detection) do not come at the expense of ease of preparation: the one-step covalent modification can be completed in minutes, using standard electrochemical cells and equipment. Also, the procedure uses robust, commercially available HOPG substrates that can be reused by mechanical exfoliation many times, lowering the operational cost and further increasing wide accessibility and attractiveness of our approach. The fundamental reasons for the high performance of the sensor may be related to its simple and well-defined structure, in which all the sensing units (covalently attached β-CD-moieties) are positioned uniformly and close to the collector surface (HOPG). This is achieved by the chemical characteristics of both reagent (a highly reactive, but sterically hindered diazonium compound, yielding monolayer modification exclusively) and substrate (low-reactive sp2 carbon surface, requiring highly reactive radical reagents for its modification), resulting in negligible side reactions despite the simplicity of the approach. These principles, and the resulting performance, can be taken as a proof of concept for entirely different sensors, e.g. using other van der Waals solids as substrates, but based on analogous chemistries.

The modification of solid surfaces with supramolecular hosts is a powerful method to tailor interfacial properties and confer chemical selectivity, but often involves multistep protocols that hinder facile upscaling. Here, the one-step covalent modification of highly oriented pyrolytic graphite (HOPG) with a beta-cyclodextrin (beta-CD) derivative, which efficiently forms inclusion complexes with hydrophobic guests of suitable size, is demonstrated. The grafted beta-CD-HOPG surface is investigated toward electrochemical detection of ferrocene and dopamine. The enrichment of the analytes at the electrode surface, through inclusion in beta-CD, leads to an enhanced electrochemical response and an improved detection limit. Furthermore, the modified beta-CD-HOPG electrode discriminates analytes that form host-guest complexes with beta-CD against a 100-fold higher background of electroactive substances that do not. Atomic force microscopy, scanning tunneling microscopy, and Raman spectroscopy confirm the covalent nature of the modification and reveal high stability toward solvent rinsing, ultrasonication, and temperatures up to 140 degrees C. The one-step covalent modification therefore holds substantial promise for the routine production of inexpensive, yet robust and highly performant electrochemical sensors. Beyond electrochemical sensor development, our strategy is valuable to prepare materials where accurate spatial positioning of functional units and efficient current collection are crucial, e.g. in photoelectrodes or electrocatalysts.

Partial hydrolysis of poly(2-oxazoline)s yields poly[(2-oxazoline)-co-(ethylenimine)] copolymers that are of interest for a broad range of applications, from switchable surfaces, nanoparticles and hydrogels, to gene delivery and biosensors. In the present research, a fast and reproducible method is developed to obtain poly[(2-ethyl-2-oxazoline)-co-(ethylenimine)] (P(EtOx-co-EI)) copolymers via acid-catalyzed partial hydrolysis of poly(2-ethyl-2-oxazoline) (PEtOx). The hydrolysis kinetics were investigated by 1H-NMR spectroscopy and size exclusion chromatography using hexafluoroisopropanol as eluent. It was found that the hydrolysis was greatly accelerated by increasing the temperature from 100 °C up to near-critical water (275 °C) using microwave reactors; similar results were obtained in conventional pressure reactors at 180 °C. The optimal hydrolysis with regard to speed and control over the final copolymer structure was achieved at 180 °C, since the polymer was found to degrade and decompose above this temperature. In addition, control over the desired degree of hydrolysis of PEtOx was obtained by selecting the appropriate HCl concentration. To summarize, this work reports on defining optimal conditions to achieve tailored P(EtOx-co-EI) copolymers in a fast and reproducible way, utilizing high temperatures and controlled acidic conditions.

Polymers with thermoresponsive properties have received a strong interest due to their potential applications. Here we report the synthesis and characterisation of a water soluble and thermoresponsive polythiophene derivative. Firstly, a polythiophene phenylene (PThP) functionalised with an initiator for atom transfer radical polymerization (ATRP) and azide groups on the side chains was synthesised. Secondly, ATRP was employed to graft poly(ethylene glycol) methacrylate (PEGMA) from the PThP to create a permanently water soluble conjugated polymer. Further functionalisation was then conducted through the ‘click’ reaction with propargyl functionalised poly(2-n-propyl-2-oxazoline) to introduce thermoresponsivness. The polymer displayed lower critical solution temperature (LCST) behavior, as revealed by fluorescence and UV-Vis spectroscopy with potential use as soluble polymeric thermometer.

International audience; Most polymeric thermoresponsive hydrogels contract upon heating beyond the lower critical solution temper-ature (LCST) of the polymers used. Herein, we report a supramolecular hydrogel system that shows the opposite temperature dependence. When the non-thermosesponsive hydrogel NaphtGel, containing dialkoxynaphthalene guest molecules,becomes complexed with the tetra cationic macro-cyclic host CBPQT4+, swelling occurred as a result of host–guest complex formation leading to charge repulsion between the host units,aswell as an osmotic contribution of chloride counter-ions embedded in the network. The immersion of NaphtGel in a solution of poly(N-isopropylacrylamide) with tetrathiafulvalene (TTF) end groups complexed with CBPQT4+ induced positive thermoresponsive behaviour. The LCST-induced dethreading of the polymer-based pseudoro-taxane upon heating led to transfer of the CBPQT4+ host and a concomitant swelling of NaphtGel. Subsequent cooling led to reformation of the TTF-based host–guest complexes in solution and contraction of the hydrogel.

The first symposium on poly(2-oxazo-line)s and related pseudo-polypeptide structures was held as part of the 243rd American Chemical Society National Meeting in San Diego (CA) from the 27th to the 29th of March 2012. The scientists will gather again to discuss the progress in the field at the second symposium on poly(2-oxazoline)s and pseudo-polypeptides at the ACS National Meeting in San Francisco, to be held in August 2014.

International audience; Thermoresponsive polymers facilitate the development of a wide range of applications in multiple areas spanning from construction or water management to lab-on-a-chip technologies and biomedical sciences. The combination of thermoresponsive polymers with supramolecular chemistry, inspired by the molecular mechanisms behind natural systems, is resulting in adaptive and smart materials with unprecedented properties. This work reviews the past advances on the combination of this young field of research with polymer chemistry that is enabling a high level of control on polymer architecture and stimuli-responsiveness in solution. We will discuss how such polymer systems are able to store thermal information, respond to multiple stimuli in a reversible manner, or adapt their morphology on demand, all powered by the synergy between polymer chemistry and supramolecular chemistry.

Functionalised nanomaterials are gaining popularity for use as drug delivery vehicles and, in particular, mucus penetrating nanoparticles may improve drug bioavailability via the oral route. To date, few polymers have been investigated for their muco-penetration, and the effects of systematic structural changes to polymer architectures on the penetration and diffusion of functionalised nanomaterials through mucosal tissue have not been reported. We investigated the influence of poly(2-oxazoline) alkyl side chain length on nanoparticle diffusion; poly(2-methyl-2-oxazoline), poly(2-ethyl-2-oxazoline), and poly (2-n-propyl-2-oxazoline) were grafted onto the surface of thiolated silica nanoparticles and characterised by FT-IR, Raman and NMR spectroscopy, thermogravimetric analysis, and small angle neutron scattering. Diffusion coefficients were determined in water and in a mucin dispersion (using Nanoparticle Tracking Analysis), and penetration through a mucosal barrier was assessed using an ex vivo fluorescence technique. The addition of a single methylene group in the side chain significantly altered the penetration and diffusion of the materials in both mucin dispersions and mucosal tissue. Nanoparticles functionalised with poly(2-methyl-2-oxazoline) were significantly more diffusive than particles with poly(2-ethyl-2-oxazoline) while particles with poly(2-n-propyl-2-oxazoline) showed no significant increase compared to the unfunctionalised particles. These data show that variations in the polymer structure can radically alter their diffusive properties with clear implications for the future design of mucus penetrating systems.

A new class of polymeric thermometers with a memory function is reported that is based on the supramolecular host-guest interactions of poly(N-isopropylacrylamide) (PNIPAM) with side-chain naphthalene guest moieties and the tetracationic macrocycle cyclobis(paraquat-p-phenylene) (CBPQT(4+)) as the host. This supramolecular thermometer exhibits a memory function for the thermal history of the solution, which arises from the large hysteresis of the thermoresponsive LCST phase transition (LCST = lower critical solution temperature). This hysteresis is based on the formation of a metastable soluble state that consists of the PNIPAM-CBPQT(4+) host-guest complex. When heated above the transition temperature, the polymer collapses, and the host-guest interactions are disrupted, making the polymer more hydrophobic and less soluble in water. Aside from providing fundamental insights into the kinetic control of supramolecular assemblies, the developed thermometer with a memory function might find use in applications spanning the physical and biological sciences.

The conjunction of polymers and medicine enables the development of new materials that display novel features, opening new ways to administrate drugs, design implants and biosensors, to deliver pharmaceuticals impacting cancer treatment, regenerative medicine or gene therapy. Poly(2-oxazoline)s (POx) constitute a polymer class with exceptional properties for their use in a plethora of different biomedical applications and are proposed as a versatile platform for the development of new medicine. Herein, a global vision of POx as a platform for novel biomaterials is offered, by highlighting the recent advances and breakthroughs in this fascinating field.

Polymethacrylates such as Eudragit® polymers are well established as drug delivery matrix. Here, we synthesize several Eudragit E PO (n-butyl-, dimethylaminoethyl-, methyl-methacrylate-terpolymer) analogues via free radical polymerization. These polymers are processed via hot melt extrusion, followed by injection molding and evaluated as carriers to produce immediate release solid solution tablets. Three chemical modifications increased the glass transition temperature of the polymer: (a) substitution of n-butyl by t-butyl groups, (b) reduction of the dimethylaminoethyl methacrylate (DMAEMA) content, and (c) incorporation of a bulky isobornyl repeating unit. These structural modifications revealed the possibility to increase the mechanical stability of the tablets via altering the polymer Tg without influencing the drug release characteristics and glassy solid solution forming properties. The presence of DMAEMA units proved to be crucial with respect to API/polymer interaction (essential in creating glassy solid solutions) and drug release characteristics. Moreover, these chemical modifications accentuate the need for a more rational design of (methacrylate) polymer matrix excipients for drug formulation via hot melt extrusion and injection molding.

The ability of merging the properties of poly(2-oxazoline)s and poly(ethylene imine) is of high interest for various biomedical applications, including gene delivery, biosensors, and switchable surfaces and nanoparticles. In the present research, a methodology for the controlled and selective hydrolysis of (co)poly(2-oxazoline)s is developed in an ethanol-water solvent mixture, opening the path toward a wide range of block poly(2-oxazoline-co-ethylene imine) (POx-PEI) copolymers with tunable properties. The unexpected influence of the selected ethanol-water binary solvent mixture on the hydrolysis kinetics and selectivity is highlighted in the pursue of well-defined POx-PEI block copolymers.

Correction for ‘Tuning temperature responsive poly(2-alkyl-2-oxazoline)s by supramolecular host–guest interactions’ by Victor R. de la Rosa et al., Org. Biomol. Chem., 2015, 13, 3048–3057.

The surprising difference in the cationic ring-opening polymerization 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 (kp) was found to decrease in the order c-PropOx > n-PropOx > i-PropOx. Theoretical free energy calculations confirmed the trend for kp, 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 ...