Corrigendum: Tough materials through ionic interactions.

[This corrects the article DOI: 10.3389/fchem.2021.721656.].

Soft Poly(N-vinylcaprolactam) Based Aqueous Particles.

Soft nanoparticles are an important class of material with potential to be used as carriers of active compounds. Swollen, penetrable particles can act as a host for the active ingredients and provide stability, stimuli-responsiveness and recyclability for the guest. Thermoresponsive colloidal gel particles are especially attractive for such applications due to the extremely soft structure, size and responsiveness. Poly(N-vinylcaprolactam) (PNVCL) is a much studied, popular thermoresponsive polymer. The polymer has low toxicity and the phase transition temperature is close to body temperature. During the phase transition, the polymer becomes less soluble, the particle expels a large part of water and the particle collapses to a more compact form. The diffusion of material in and from the particles is largely affected by this transition.  As the solubility of the polymer changes, so do the interactions with the loaded compound.  This feature article focuses on the synthetic methods, properties and applications of soft PNVCL particles.

Thermo-Reversible Cellulose Micro Phase-Separation in Mixtures of Methyltributylphosphonium Acetate and γ-Valerolactone or DMSO.

We have identified cellulose solvents, comprised of binary mixtures of molecular solvents and ionic liquids that rapidly dissolve cellulose to high concentration and show upper-critical solution temperature (UCST)-like thermodynamic behaviour - upon cooling and micro phase-separation to roughly spherical microparticle particle-gel mixtures. This is a result of an entropy-dominant process, controllable by changing temperature, with an overall exothermic regeneration step. However, the initial dissolution of cellulose in this system, from the majority cellulose I allomorph upon increasing temperature, is also exothermic. The mixtures essentially act as 'thermo-switchable' gels. Upon initial dissolution and cooling, micro-scaled spherical particles are formed, the formation onset and size of which are dependent on the presence of traces of water. Wide-angle X-ray scattering (WAXS) and 13 C cross-polarisation magic-angle spinning (CP-MAS) NMR spectroscopy have identified that the cellulose micro phase-separates with no remaining cellulose I allomorph and eventually forms a proportion of the cellulose II allomorph after water washing and drying. The rheological properties of these solutions demonstrate the possibility of a new type of cellulose processing, whereby morphology can be influenced by changing temperature.

Phase Separation of Aqueous Poly(diisopropylaminoethyl methacrylate) upon Heating.

Poly(diisopropylaminoethyl methacrylate) (PDPA) is a pH- and thermally responsive water-soluble polymer. This study deepens the understanding of its phase separation behavior upon heating. Phase separation upon heating was investigated in salt solutions of varying pH and ionic strength. The effect of the counterion on the phase transition upon heating is clearly demonstrated for chloride-, phosphate-, and citrate-anions. Phase separation did not occur in pure water. The buffer solutions exhibited similar cloud points, but phase separation occurred in different pH ranges and with different mechanisms. The solution behavior of a block copolymer comprising poly(dimethylaminoethyl methacrylate) (PDMAEMA) and PDPA was investigated. Since the PDMAEMA and PDPA blocks phase separate within different pH- and temperature ranges, the block copolymer forms micelle-like structures at high temperature or pH.

CO2 Capture and Low-Temperature Release by Poly(aminoethyl methacrylate) and Derivatives.

Poly(aminoethyl methacrylate) (PAEMA), poly(ethylene oxide)-block-(aminoethyl methacrylate) (PEO-PAEMA), and their guanidinylated derivates, poly(guanidine ethyl methacrylate) (PGEMA) and poly(ethylene oxide)-block-(guanidine ethyl methacrylate) (PEO-PGEMA), were prepared to study their capabilities for CO2 adsorption and release. The polymers of different forms or degree of guanidinylation were thoroughly characterized, and their interaction with CO2 was studied by NMR and calorimetry. The extent and kinetics of adsorption and desorption of N2 and CO2 were investigated by thermogravimetry under controlled gas atmospheres. The materials did not adsorb N2, whereas CO2 could be reversibly adsorbed at room temperature and released by an elevated temperature. The most promising polymer was PGEMA with a guanidinylation degree of 7% showing a CO2 adsorption capacity of 2.4 mmol/g at room temperature and a desorption temperature of 72 °C. The study also revealed relations between the polymer chemical composition and CO2 adsorption and release characteristics that are useful in future formulations for CO2 adsorbent polymer materials.

Tough Materials Through Ionic Interactions.

This article introduces butyl acrylate-based materials that are toughened with dynamic crosslinkers. These dynamic crosslinkers are salts where both the anion and cation polymerize. The ion pairs between the polymerized anions and cations form dynamic crosslinks that break and reform under deformation. Chemical crosslinker was used to bring shape stability. The extent of dynamic and chemical crosslinking was related to the mechanical and thermal properties of the materials. Furthermore, the dependence of the material properties on different dynamic crosslinkers-tributyl-(4-vinylbenzyl)ammonium sulfopropyl acrylate (C4ASA) and trihexyl-(4-vinylbenzyl)ammonium sulfopropyl acrylate (C6ASA)-was studied. The materials' mechanical and thermal properties were characterized by means of tensile tests, dynamic mechanical analysis, differential scanning calorimetry, and thermogravimetric analysis. The dynamic crosslinks strengthened the materials considerably. Chemical crosslinks decreased the elasticity of the materials but did not significantly affect their strength. Comparison of the two ionic crosslinkers revealed that changing the crosslinker from C4ASA to C6ASA results in more elastic, but slightly weaker materials. In conclusion, dynamic crosslinks provide substantial enhancement of mechanical properties of the materials. This is a unique approach that is utilizable for a wide variety of polymer materials.

Self-Organization in Dilute Aqueous Solutions of Thermoresponsive Star-Shaped Six-Arm Poly-2-Alkyl-2-Oxazines and Poly-2-Alkyl-2-Oxazolines.

The behavior of star-shaped six-arm poly-2-alkyl-2-oxazines and poly-2-alkyl-2-oxazolines in aqueous solutions on heating was studied by light scattering, turbidimetry and microcalorimetry. The core of stars was hexaaza [26] orthoparacyclophane and the arms were poly-2-ethyl-2-oxazine, poly-2-isopropyl-2-oxazine, poly-2-ethyl-2-oxazoline, and poly-2-isopropyl-2-oxazoline. The arm structure affects the properties of polymers already at low temperatures. Molecules and aggregates were present in solutions of poly-2-alkyl-2-oxazines, while aggregates of two types were observed in the case of poly-2-alkyl-2-oxazolines. On heating below the phase separation temperature, the characteristics of the investigated solutions did not depend practically on temperature. An increase in the dehydration degree of poly-2-alkyl-2-oxazines and poly-2-alkyl-2-oxazolines led to the formation of intermolecular hydrogen bonds, and aggregation was the dominant process near the phase separation temperature. It was shown that the characteristics of the phase transition in solutions of the studied polymer stars are determined primarily by the arm structure, while the influence of the molar mass is not so significant. In comparison with literature data, the role of the hydrophobic core structure in the formation of the properties of star-shaped polymers was analyzed.

Phase Transition Behavior and Catalytic Activity of Poly(N-acryloylglycinamide-co-methacrylic acid) Microgels.

Poly(N-acryloyl glycinamide) is a well-known thermoresponsive polymer possessing an upper critical solution temperature (UCST) in water. By copolymerizing N-acryloyl glycinamide (NAGA) with methacrylic acid (MAA) in the presence of a crosslinker, poly(N-acryloyl glycinamide-co-methacrylic acid) [P(NAGA-MAA)] copolymer microgels with an MAA molar fraction of 10-70 mol % were obtained. The polymerization kinetics suggests that the copolymer microgels have a random structure. The size of the microgels was between 60 and 120 nm in the non-aggregated swollen state in aqueous medium and depending on the solvent conditions, they show reversible swelling and shrinking upon temperature change. Their phase transition behavior was studied by a combination of methods to understand the process of the UCST-type behavior and interactions between NAGA and MAA. P(NAGA-MAA) microgels were loaded with silver nanoparticles (AgNPs) by the reduction of AgNO3 under UV light. Compared with the chemical reduction of AgNO3, the photoreduction results in smaller AgNPs and the amount and size of the AgNPs are dependent on the comonomer ratio. The catalytic activity of the AgNP-loaded microgels in 4-nitrophenol reduction was tested.

Polyzwitterions with LCST Side Chains: Tunable Self-Assembly.

Manipulation of self-assembly behavior of copolymers via environmental change is attractive in the fabrication of smart polymeric materials. We present tunable self-assembly behavior of graft copolymers, poly(sulfobetaine methacrylate)-graft-poly[oligo(ethylene glycol) methyl ether methacrylate)-co-di(ethylene glycol) methyl ether methacrylate] (PSBM-g-P(OEGMA-co-DEGMA)). Upon heating the aqueous solutions, the graft copolymers undergo a transition from micelles with PSBM cores to unimers (i.e., individual macromolecules) and then to reversed micelles with P(OEGMA-co-DEGMA) cores, thus demonstrating the tunability of the self-assembling through temperature change. In the presence of salt the temperature response of PSBM is eliminated, and the structure of the micelles with the P(OEGMA-co-DEGMA) core changes. Moreover, for the graft copolymer with long side chains, micelles with aggregation number ∼ 2 were formed with a PSBM core at low temperature, which is ascribed to the steric effect of the P(OEGMA-co-DEGMA) shell.

CE and asymmetrical flow-field flow fractionation studies of polymer interactions with surfaces and solutes reveal conformation changes of polymers.

Amphiphilic diblock copolymers consisting of a hydrophobic core containing a polymerized ionic liquid and an outer shell composed of poly(N-isoprolylacrylamide) were investigated by capillary electrophoresis and asymmetrical flow-field flow fractionation. The polymerized ionic liquid comprised poly(2-(1-butylimidazolium-3-yl)ethyl methacrylate tetrafluoroborate) with a constant block length (n = 24), while the length of the poly(N-isoprolylacrylamide) block varied (n = 14; 26; 59; 88). Possible adsorption of the block copolymer on the fused silica capillary, due to alterations in the polymeric conformation upon a change in the temperature (25 and 45 °C), was initially studied. For comparison, the effect of temperature on the copolymer conformation/hydrodynamic size was determined with the aid of asymmetrical flow-field flow fractionation and light scattering. To get more information about the hydrophilic/hydrophobic properties of the synthesized block copolymers, they were used as a pseudostationary phase in electrokinetic chromatography for the separation of some model compounds, that is, benzoates and steroids. Of particular interest was to find out whether a change in the length or concentration of the poly(N-isoprolylacrylamide) block would affect the separation of the model compounds. Overall, our results show that capillary electrophoresis and asymmetrical flow-field flow fractionation are suitable methods for characterizing conformational changes of such diblock copolymers.

Stimuli-Responsive Nanodiamond-Polyelectrolyte Composite Films.

Nanodiamonds (NDs) can considerably improve the mechanical and thermal properties of polymeric composites. However, the tendency of NDs to aggregate limits the potential of these non-toxic, mechanically- and chemically-robust nanofillers. In this work, tough, flexible, and stimuli-responsive polyelectrolyte films composed of cross-linked poly(butyl acrylate-co-dimethylaminoethyl methacrylate) (P(BA-co-DMAEMA)) were prepared by photopolymerization. The effects of the added carboxylate-functionalized NDs on their mechanical and stimuli-responsive properties were studied. When the negatively charged NDs were added to the polymerization media directly, the mechanical properties of the films changed only slightly, because of the uneven distribution of the aggregated NDs in the films. In order to disperse and distribute the NDs more evenly, a prepolymerized polycation block copolymer complexing agent was used during the photopolymerization process. This approach improved the mechanical properties of the films and enhanced their thermally-induced, reversible phase-transition behavior.

Glucose and Maltose Surface-Functionalized Thermoresponsive Poly(N-Vinylcaprolactam) Nanogels.

Soft nanoparticles are interesting materials due to their size, deformability, and ability to host guest molecules. Surface properties play an essential role in determining the fate of the particles in biological medium, and coating of the nanoparticles (and polymers) with carbohydrates has been found to be an efficient strategy for increasing their biocompatibility and fine-tuning other important properties such as aqueous solubility. In this work, soft nanogels of poly(N-vinylcaprolactam), PNVCL, were surface-functionalized with different glucose and maltose ligands, and the colloidal properties of the gels were analyzed. The PNVCL nanogels were first prepared via semibatch precipitation polymerization, where a comonomer, propargyl acrylate (PA), was added after preparticle formation. The aim was to synthesize "clickable" nanogels with alkyne groups on their surfaces. The nanogels were then functionalized with two separate azido-glucosides and azido-maltosides (containing different linkers) through a copper-catalyzed azide-alkyne cycloaddition (CuAAc) click reaction. The glucose and maltose bearing nanogels were thermoresponsive and shrank upon heating. Compared to the PNVCL-PA nanogel, the carbohydrate bearing ones were larger, more hydrophilic, had volume phase transitions at higher temperatures, and were more stable against salt-induced precipitation. In addition to investigating the colloidal properties of the nanogels, the carbohydrate recognition was addressed by studying the interactions with a model lectin, concanavalin A (Con A). The binding efficiency was not affected by the temperature, which indicates that the carbohydrate moieties are located on the gel surfaces, and are capable of interacting with other biomolecules independent of temperature. Thus, the synthesis produces nanogels, which have surface functions capable of biorelevant interactions and a thermoresponsive structure. These types of particles can be used for drug delivery.

Poly(2-propyl-2-oxazoline)s in Aqueous Methanol: To Dissolve or not to Dissolve.

At room temperature, poly(N-isopropylacrylamide) (PNIPAM) is soluble in water and methanol, but it is not soluble in certain water/methanol mixtures. This phenomenon, known as cononsolvency, has been explored in great detail experimentally and theoretically in an attempt to understand the complex interactions occurring in the ternary PNIPAM/water/co-nonsolvent system. Yet little is known about the effects of the polymer structure on cononsolvency. To address this point, we investigated the temperature-dependent solution properties in water, methanol, and mixtures of the two solvents of poly(2-cyclopropyl-2-oxazoline) (PcyPOx) and two structural isomers of PNIPAM (M n ∼ 11 kg/mol): poly(2-isopropyl-2-oxazoline) (PiPOx) and poly(2-n-propyl-2-oxazoline) (PnPOx). The phase diagram of the ternary water/methanol/poly(2-propyl-2-oxazolines) (PPOx) systems, constructed based on cloud point (T CP) measurements, revealed that PnPOx exhibits cononsolvency in water/methanol mixtures. In contrast, methanol acts as a cosolvent for PiPOx and PcyPOx in water. The enthalpy, ΔH, and temperature, T max, of the coil-to-globule transition of the three polymers in various water/methanol mixtures were measured by high-sensitivity differential scanning calorimetry. T max follows the same trends as T CP, confirming the cononsolvency of PnPOx and the cosolvency of PiPOx and PcyPOx. ΔH decreases linearly as a function of the methanol content for all PPOx systems. Ancillary high-resolution 1H NMR spectroscopy studies of PPOx solutions in D2O and methanol-d 4, coupled with DOSY and NOESY experiments revealed that the n-propyl group of PnPOx rotates freely in D2O, whereas the rotation of the isopropyl and cyclopropyl groups of PiPOx and PcyPOx, respectively, is limited due to steric restriction. This factor appears to play an important role in the case of the PPOxs/water/methanol ternary system.

Molecular Mass Affects the Phase Separation of Aqueous PEG-Polycation Block Copolymer.

Mechanisms of the phase separation and remixing of cationic PEG-containing block copolymers have been investigated in aqueous lithium triflate solutions. The polycation was poly(vinylbenzyl trimethylammonium triflate). We have previously reported on one such block copolymer, which upon cooling of a hot clear solution first underwent phase separation into a turbid colloid and, later, partially cleared again with further cooling. To better understand the balance of various interactions in the solutions/dispersions, a series of polymers with varying DP of the cationic block was synthesized. From one of the polymers, the alkyl end group (a fragment of the chain transfer agent) was removed. The length of the cationic block affected critically the behavior, but the hydrophobic end group had a minimal effect. Polymers with a short cationic block turn cloudy and partially clear again during a temperature decrease, whereas those with a long cationic block phase separate and slowly precipitate and remix only when heated. Phase separation takes place via particle formation, and we suggest different mechanisms for colloidal stabilization of particles composed of short or long chains.

Poly(2-isopropyl-2-oxazoline)-b-poly(lactide) (PiPOx-b-PLA) Nanoparticles in Water: Interblock van der Waals Attraction Opposes Amphiphilic Phase Separation.

Poly(2-isopropyl-2-oxazoline)-b-poly(lactide) (PiPOx-b-PLA) diblock copolymers comprise two miscible blocks: the hydrophilic and thermosensitive PiPOx and the hydrophobic PLA, a biocompatible and biodegradable polyester. They self-assemble in water, forming stable dispersions of nanoparticles with hydrodynamic radii (R h) ranging from ∼18 to 60 nm, depending on their molar mass, the relative size of the two blocks, and the configuration of the lactide unit. Evidence from 1H nuclear magnetic resonance spectroscopy, light scattering, small-angle neutron scattering, and cryo-transmission electron microscopy indicates that the nanoparticles do not adopt the typical core-shell morphology. Aqueous nanoparticle dispersions heated from 20 to 80 °C were monitored by turbidimetry and microcalorimetry. Nanoparticles of copolymers containing a poly(dl-lactide) block coagulated irreversibly upon heating to 50 °C, forming particles of various shapes (R h ∼ 200-500 nm). Dispersions of PiPOx-b-poly(l-lactide) coagulated to a lesser extent or remained stable upon heating. From the entire experimental evidence, we conclude that PiPOx-b-PLA nanoparticles consist of a core of PLA/PiPOx chains associated via dipole-dipole interactions of the PLA and PiPOx carbonyl groups. The core is surrounded by tethered PiPOx loops and tails responsible for the colloidal stability of the nanoparticles in water. While the core of all nanoparticles studied contains associated PiPOx and PLA blocks, fine details of the nanoparticles morphology vary predictably with the size and composition of the copolymers, yielding particles of distinctive thermosensitivity in aqueous dispersions.

Artificial chaperones based on thermoresponsive polymers recognize the unfolded state of the protein.

Stabilization of the enzymes under stress conditions is of special interest for modern biochemistry, bioengineering, as well as for formulation and target delivery of protein-based drugs. Aiming to achieve an efficient stabilization at elevated temperature with no influence on the enzyme under normal conditions, we studied chaperone-like activity of thermoresponsive polymers based on poly(dimethylaminoethyl methacrylate) (PDMAEMA) toward two different proteins, glyceraldehyde-3-phosphate dehydrogenase and chicken egg lysozyme. The polymers has been shown to do not interact with the folded protein at room temperature but form a complex upon heating to either protein unfolding or polymer phase transition temperature. A PDMAEMA-PEO block copolymer with a dodecyl end-group (d-PDMAEMA-PEO) as well as PDMAEMA-PEO without the dodecyl groups protected the denatured protein against aggregation in contrast to PDMAEMA homopolymer. No effect of the polymers on the enzymatic activity of the client protein was observed at room temperature. The polymers also partially protected the enzyme against inactivation at high temperature. The results provide a platform for creation of artificial chaperones with unfolded protein recognition which is a major feature of natural chaperones.

Hyaluronic Acid Graft Copolymers with Cleavable Arms as Potential Intravitreal Drug Delivery Vehicles.

Treatment of retinal diseases currently demands frequent intravitreal injections due to rapid clearance of the therapeutics. The use of high molecular weight polymers can extend the residence time in the vitreous and prolong the injection intervals. This study reports a water soluble graft copolymer as a potential vehicle for sustained intravitreal drug delivery. The copolymer features a high molecular weight hyaluronic acid (HA) backbone and poly(glyceryl glycerol) (PGG) side chains attached via hydrolysable ester linkers. PGG, a polyether with 1,2-diol groups in every repeating unit available for conjugation, serves as a detachable carrier. The influence of synthesis conditions and incubation in physiological media on the molecular weight of HA is studied. The cleavage of the PGG grafts from the HA backbone is quantified and polymer-from-polymer release kinetics are determined. The biocompatibility of the materials is tested in different cell cultures.

Size, Stability, and Porosity of Mesoporous Nanoparticles Characterized with Light Scattering.

Silicon-based mesoporous nanoparticles have been extensively studied to meet the challenges in the drug delivery. Functionality of these nanoparticles depends on their properties which are often changing as a function of particle size and surrounding medium. Widely used characterization methods, dynamic light scattering (DLS), and transmission electron microscope (TEM) have both their weaknesses. We hypothesize that conventional light scattering (LS) methods can be used for a rigorous characterization of medium sensitive nanoparticles' properties, like size, stability, and porosity. Two fundamentally different silicon-based nanoparticles were made: porous silicon (PSi) from crystalline silicon and silica nanoparticles (SN) through sol-gel process. We studied the properties of these mesoporous nanoparticles with two different multiangle LS techniques, DLS and static light scattering (SLS), and compared the results to dry-state techniques, TEM, and nitrogen sorption. Comparison of particle radius from TEM and DLS revealed significant overestimation of the DLS result. Regarding to silica nanoparticles, the overestimation was attributed to agglomeration by analyzing radius of gyration and hydrodynamic radius. In case of PSi nanoparticles, strong correlation between LS result and specific surface area was found. Our results suggest that the multiangle LS methods could be used for the size, stability, and structure characterization of mesoporous nanoparticles.

Visualization data on the freezing process of micrometer-scaled aqueous citric acid drops.

The visualization data (8 movies) presented in this article are related to the research article entitled "Freezing and glass transitions upon cooling and warming and ice/freeze-concentration-solution morphology of emulsified aqueous citric acid" (A. Bogdan, M.J. Molina, H. Tenhu, 2016) [1]. The movies recorded in-situ with optical cryo-miscroscopy (OC-M) demonstrate for the first time freezing processes that occur during the cooling and subsequent warming of emulsified micrometer-scaled aqueous citric acid (CA) drops. The movies are made publicly available to enable critical or extended analyzes.

Freezing and glass transitions upon cooling and warming and ice/freeze-concentration-solution morphology of emulsified aqueous citric acid.

Although freeze-induced phase separation and the ice/FCS (freeze-concentration solution) morphology of aqueous solutions play an important role in fields ranging from life sciences and biotechnology to geophysics and high-altitude ice clouds, their understanding is far from complete. Herein, using differential scanning calorimetry (DSC) and optical cryo-microscope (OC-M), we have studied the freezing and glass transition behavior and the ice/FCS morphology of emulsified 10-60wt% CA (citric acid) solutions in the temperature region of ∼308and153K. We have obtained a lot of new result which are understandable and unclear. The most essential understandable results are as follows: (i) similar to bulk CA/H2O, emulsified CA/H2O also freezes upon cooling and warming and (ii) the ice/FCS morphology of frozen drops smaller than ∼3-4µm is less ramified than that of frozen bulk solutions. Unclear results, among others, are as follows: (i) in contrast to bulk solutions, which produce one freezing event, emulsified CA/H2O produces two freezing events and (ii) in emulsions, drop concentration is not uniform. Our results demonstrate that DSC thermograms and OC-M images/movies are mutually supplementary and allow us to extract important information which cannot be gained when DSC and OC-M techniques are used alone.