Upper Critical Solution Temperature Behavior Research Articles

Synergistic Approaches in the Design and Applications of UCST Polymers.

This review summarizes recent progress in the synergistic design strategy for thermoresponsive polymers possessing an upper critical solution temperature (UCST) in aqueous systems. To achieve precise control of the responsive behavior of the UCST polymers, their molecular design can benefit from a synergistic effect of hydrogen bonding with other interactions or modification of the chemical structures. The combination of UCST behavior with other stimuli-responsive properties of the polymers may yield new functional materials with potential applications such as sensors, actuators, and controlled release devices. The advances in this area provide insight or inspiration into the understanding and design of functional UCST polymers for a wide range of applications.

Secondary Structure-Governed Phase Separation Behavior in Glutamate-Based Polypeptides.

The phase separation behavior of biomacromolecules plays a key role in the fields of biology and medicine. In this work, we gain a deep insight into how the primary and secondary structures govern and regulate the phase separation behavior of polypeptides. To this end, we synthesized a series of polypeptides with tailorable hydroxyl-containing side chains. The secondary structure of polypeptides can be modulated by the local chemical environment and content of side chains. Interestingly, these polypeptides with different helical contents exhibited upper critical solution temperature behavior with marked differences in the cloud point temperature (Tcp) and the width of hysteresis. The phase transition temperature is highly relevant to the content of secondary structure and interchain interactions of polypeptides. The aggregation/deaggregation and the transition of secondary structure are completely reversible during heating-cooling cycles. Much to our surprise, the recovery rate of the α-helical structure governs the width of hysteresis. This work establishes the structure-property relationship between the secondary structure and phase separation behavior of the polypeptide and delivers new insight into the rational design of peptide-based materials with tailor-made phase separation behavior.

Effect of phenolic acids on temperature-sensitive property of self-assembly of ionic pair of poly(ethylene imine)/(phenylthio)acetic acid

The ionic pair self-assembly (IPSAM) composed of poly(ethyleneimine) (PEI) and (phenylthio)acetic acid (PTA) was prepared and the effect of phenolic acids (PAs) (e.g. cinnamic acid (CA), hydroxycinnamic acid (HCA), and dihydroxycinnamic acid (DHCA)) on the upper critical solution temperature (UCST) and the temperature-responsive releasing property of IPSAM were investigated. PEI/PTA ionic pair showed a UCST behavior and the PAs decreased the UCST effectively in the order of DHCA > HCA > CA. The PAs were thought to attach to the PEI chain of PEI/PTA ionic pair as pendants. PEI/PTA(3/7) ionic pair was found to be air/water interface-active. CA had little effect on the interfacial activity of the ionic pair. HCA and DHCA significantly decreased the interfacial activity. IPSAM was found as nanoparticles whose diameter was tens of nanometer and PAs had little effect on the shape and the size of IPSAM. The release degree of cargo loaded in IPSAM increased slowly with time lapse when below UCST. Whereas, the release degree increased rapidly with time lapse when above UCST, possibly because of the thermally-induced disintegration of IPSAM.

Acrylamidevinyl acetate copolymer as a new UCST copolymer: Phase transition and aggregation behavior; an experimental and theoretical study

A high sensitive upper critical solution temperature (UCST) copolymer was synthesized through free radical copolymerization with acrylamide (AAm) and vinyl acetate (VA). The UCST behavior is due to a combination of hydrogen bonds and electrostatic potentials between copolymer chains. Turbidimetry, dynamic light scattering, and rheology studies were used to determine the phase transition and aggregation behavior. It is indicated that copolymer with 80% AAm has a phase transition temperature between 38 and 38.2 °C, which is suitable for releasing fever medicine. Also, the temperature gradient for the complete dissolution of the copolymer is 2 °C. The molecular dynamics simulations at a molecular level confirmed the experimental results and indicated that aggregation of copolymer chains below UCST temperature had increased binding energy between polymer chains. The low cytotoxicity and its desirable UCST behavior make the copolymer promising for biomedical applications in the future.

Thermo-Responsive Polyion Complex of Polysulfobetaine and a Cationic Surfactant in Water

Poly(4-((3-methacrylamidopropyl)dimethylammonium)butane-1-sulfonate) (PSBP) was prepared via controlled radical polymerization. PSBP showed upper critical solution temperature (UCST) behavior in aqueous solutions, which could be controlled by adjusting the polymer and NaCl concentrations. Owing to its pendant sulfonate anions, PSBP exhibited a negative zeta potential of −7.99 mV and formed a water-soluble ion complex with the cationic surfactant cetyltrimethylammonium bromide (CTAB) via attractive electrostatic interaction. A neutral PSBP/CTAB complex was formed under equimolar concentrations of the pendant sulfonate group in PSBP and the quaternary ammonium group in CTAB. Transmittance electron microscopic images revealed the spherical shape of the complex. The stoichiometrically neutral-charge PSBP/CTAB complex exhibited UCST behavior in aqueous solutions. Similar to PSBP, the phase transition temperature of the PSBP/CTAB complex could be tuned by modifying the polymer and NaCl concentrations. In 0.1 M aqueous solution, the PSBP/CTAB complex showed UCST behavior at a low complex concentration of 0.084 g/L, whereas PSBP did not exhibit UCST behavior at concentrations below 1.0 g/L. This observation suggests that the interaction between PSBP and CTAB in the complex was stronger than the interpolymer interaction of PSBP.

The Removal of Hydrophobic Matter from Thermosensitive Poly[oligo(ethylene glycol) Monomethyl Ether Acrylate] Gel Adsorbent in Alcohol-Water Mixtures.

A thermosensitive gel that exhibits lower critical solution temperature (LCST) becomes hydrophilic at low temperatures and hydrophobic at high temperatures in water. A system for absorbing hydrophobic organic matters that exploits this property has been reported. While washing the gel at a low temperature with a good solvent is a possible method for removing the adsorbed matter, a process that then shrinks the gel is also required. Herein, we focused on poly[oligo(ethylene glycol) mono(m)ethyl ether acrylate] (POEGA) gels as thermosensitive gels suitable for use in this system. POEGAs are known to contain poly(ethylene glycol) (PEG) units in their side chains and exhibit upper critical solution temperature (UCST) behavior in aliphatic alcohols. By exploiting this property, we developed a method for removing hydrophobic matters that accumulate in these gels; we also evaluated the LCST and UCST behavior of POEGA gels in alcohol–water mixtures, and measured the LCSTs of these gels in water and their UCSTs in some alcohols.

Design of a UCST Polymer with Strong Hydrogen Bonds and Reactive Moieties for Facile Polymer-Protein Hybridization.

Polymer-protein hybrids have been extensively used in biomedical fields. Polymers with upper critical solution temperature (UCST) behaviors can form a hydrated coacervate phase below the cloud point (Tcp), providing themselves the opportunity to directly capture hydrophilic proteins and form hybrids in aqueous solutions. However, it is always a challenge to obtain a UCST polymer that could aggregate at a high temperature at a relatively low concentration and also efficiently bind with proteins. In this work, a UCST polymer reactive with proteins was designed, and its temperature responsiveness and protein-capture ability were investigated in detail. The polymer was synthesized by the reversible addition-fragmentation chain transfer (RAFT) polymerization of acrylamide (AAm) and N-acryloxysuccinimide (NAS). Interestingly, taking advantage of the partial hydrolysis of NAS into acrylic acid (AAc), the obtained P(AAm-co-NAS-co-AAc) polymer exhibited an excellent UCST behavior and possessed good protein-capture ability. It showed a relatively higher Tcp (81 °C) at a lower concentration (0.1 wt %) and quickly formed polymer-protein hybrids with high protein loading and without losing protein bioactivity, and both the polymer and polymer-protein nanoparticles showed good cytocompatibility. All the findings are attributed to the unique structure of the polymer, which provided not only the strong and stable hydrogen bonds but also the quick and mild reactivity. The work offers an easy and mild strategy for polymer-protein hybridization directly in aqueous solutions, which may find applications in biomedical fields.

Poly(N-cyanoethylacrylamide), a new thermoresponsive homopolymer presenting both LCST and UCST behavior in water

Novel dual thermoresponsive N-cyanoethylacrylamide (CEAm)-based (co)polymers synthesized by RAFT polymerization display a lower critical solution temperature (LCST) and an upper critical solution temperature (UCST) in water.

Temperature effects on alcohol aggregation phenomena and phase behavior in n-butanol aqueous solution

Liquid-liquid phase separation is an important phenomenon that prevails from simple to complex molecular systems where temperature plays a crucial role in the fundamental understanding of phase behavior in a theoretical and industrial perspective. The n-butanol aqueous solutions have two separate liquid phases of alcohol-rich and water-rich formed at room temperature. The change in phase behavior occurs from two phases to one with an increase of temperature, exhibiting an upper critical solution temperature (UCST) behavior. We carried out molecular dynamics simulations and graph theoretical analysis to understand how temperature regulates n-butanol aggregation and the network properties of water at various concentrations.The theoretical studies suggest that the n-butanol molecules form two distinct alcohol aggregates, water-compatible or water-incompatible, determined by the interactions between alcohol and solvent molecules. Moreover, the proposed bifurcating aggregation pathway is sensitive to the temperature and composition of the n-butanol aqueous solution. The current study shows how temperature is significant in modulating the alcohol aggregation behavior and affects water structure which determines the phase behavior of aqueous solution systems. The effect of temperature on the alcohol aggregation pattern and water structure in n-butanol/water mixtures provides a critical clue in the fundamental understanding and determining the phase behavior of binary water mixtures. The current study also provides a molecular framework to examine and govern the UCST behavior of aqueous solution systems.

Nonionic Polymer with Flat Upper Critical Solution Temperature Behavior in Water.

We rationally designed a monomer that when polymerized formed a well-defined nonionic polymer [poly(2-(methacryloyloxy) ethylureido glycinamide), PMEGA] by reversible addition fragmentation chain transfer with a flat and tunable upper critical solution temperature (UCST) in water. The monomer was made in one pot from commercially available compounds and with ease of purification. Strong hydrogen-bonding side groups on the polymer produced sharp coil-to-globule transitions upon cooling below its UCST. Ideal random copolymers produced with butyl methacrylate also showed flat UCST profiles, in which the UCST increased with a greater butyl methacrylate copolymer composition from 7 to 65 °C. In the presence of NaCl, the UCST decreased linearly with NaCl concentration due to the "salting-in" effect, and it was found that the slopes from the linear decrease of UCST were nearly identical for all copolymer compositions. This new polymer and its copolymers support the hypothesis that strong hydrogen bonding between the side groups allowed the flat UCST to be readily tuned with a high level of predictability. We postulate that this polymer system may provide wide biological applicability similar to that found for the well-used flat lower critical solution temperature (LCST) of poly(N-isopropylacrylamide).

Stimuli-Responsive Aggregation of High Molar Mass Poly(N,N-Diethylacrylamide)-b-Poly(4-Acryloylmorpholine) in Tetrahydrofuran.

The self-assembly of block copolymers constitutes a timely research area in polymer science with implications for applications like sensing or drug-delivery. Here, the unprecedented aggregation behavior of high molar mass block copolymer poly(N,N-diethylacrylamide)-b-poly(4-acryloylmorpholine) (PDEA-b-PAM) (Mn >400kg mol-1 ) in organic solvent tetrahydrofuran (THF) is investigated. To elucidate the aggregation, dynamic light scattering, cryo-transmission electron microscopy, and turbidimetry are employed. The aggregate formation is assigned to the unprecedented upper critical solution temperature behavior of PAM in THF at elevated concentrations (> 6 wt.%) and high molar masses. Various future directions for this new thermo-responsive block copolymer are envisioned, for example, in the areas of photonics or templating of inorganic structures.

RAFT-Polymerized N-Cyanomethylacrylamide-Based (Co)polymers Exhibiting Tunable UCST Behavior in Water.

In this present work, the synthesis of a new family of upper critical solution temperature (UCST)-thermoresponsive polymers based on N-cyanomethylacrylamide (CMAm) is reported. It is demonstrated that the thermally initiated reversible addition fragmentation chain transfer (RAFT) polymerization of CMAm conducted in N,N-dimethylformamide (DMF) is well controlled. The homopolymer presents a sharp and reversible UCST-type phase transition in pure water with a very small hysteresis between cooling and heating cycles. It is demonstrated that the cloud point (TCP ) of poly(N-cyanomethylacrylamide) (PCMAm) is strongly molar mass dependent and shifts toward lower temperatures in saline water. Moreover, the transition temperature can be tuned over a large temperature range by copolymerization of CMAm with acrylamide or acrylic acid. The latter copolymers are both thermoresponsive and pH responsive. Interestingly, by this strategy sharp and reversible UCST-type transitions close to physiological temperature can be reached, which makes the copolymers extremely interesting candidates for biomedical applications.

Constrained thermoresponsive polymers - new insights into fundamentals and applications.

In the last decades, numerous stimuli-responsive polymers have been developed and investigated regarding their switching properties. In particular, thermoresponsive polymers, which form a miscibility gap with the ambient solvent with a lower or upper critical demixing point depending on the temperature, have been intensively studied in solution. For the application of such polymers in novel sensors, drug delivery systems or as multifunctional coatings, they typically have to be transferred into specific arrangements, such as micelles, polymer films or grafted nanoparticles. However, it turns out that the thermodynamic concept for the phase transition of free polymer chains fails, when thermoresponsive polymers are assembled into such sterically confined architectures. Whereas many published studies focus on synthetic aspects as well as individual applications of thermoresponsive polymers, the underlying structure–property relationships governing the thermoresponse of sterically constrained assemblies, are still poorly understood. Furthermore, the clear majority of publications deals with polymers that exhibit a lower critical solution temperature (LCST) behavior, with PNIPAAM as their main representative. In contrast, for polymer arrangements with an upper critical solution temperature (UCST), there is only limited knowledge about preparation, application and precise physical understanding of the phase transition. This review article provides an overview about the current knowledge of thermoresponsive polymers with limited mobility focusing on UCST behavior and the possibilities for influencing their thermoresponsive switching characteristics. It comprises star polymers, micelles as well as polymer chains grafted to flat substrates and particulate inorganic surfaces. The elaboration of the physicochemical interplay between the architecture of the polymer assembly and the resulting thermoresponsive switching behavior will be in the foreground of this consideration.

Thermoresponsive Polycation-Stabilized Nanoparticles through PISA. Control of Particle Morphology with a Salt

Poly[(vinylbenzyl) trimethylammonium chloride] (PVBTMAC) has been used as a stabilizer in the polymerization-induced self-assembly polymerizations of diacetone acrylamide (DAAM). A whole spectrum of particle morphologies was obtained simply by adjusting the ionic strength of the reaction mixtures; no dilution of the cationic charges with noncharged comonomers or with noncharged polymers was needed. In addition to the ionic strength, the effects of solid content and the length of the PDAAM block on the morphologies of the particles were studied in detail. The experiments are a continuation to previous studies on solution properties of PVBTMAC. It has been shown earlier that the solubility of the polycation may be tuned with counterions. Hydrophobic triflate ions induce an upper critical solution temperature behavior. In the present case, the chains bound to hydrophobic cores of the particles show either a one-step phase separation in aqueous triflate solutions or under certain conditions, a two-step transition. The step-wise transition is typical for responsive polymers with limited mobility.

Upper Critical Solution Temperature Behavior of pH-Responsive Amphoteric Statistical Copolymers in Aqueous Solutions.

Amphoteric statistical equivalent copolymers (P(2VP/NaSS)n) composed of 2-vinylpyridine (2VP) and anionic sodium p-styrenesulfonate (NaSS) were prepared via reversible addition–fragmentation chain transfer polymerization. The degrees of polymerization (n) were 19 and 95. The monomer reactivity ratio, time conversion profile, and 1H nuclear magnetic resonance diffusion-ordered spectra suggested that the copolymerization of 2VP and NaSS provided statistical or near to random copolymers. P(2VP/NaSS)n exhibited an upper critical solution temperature (UCST) in acidic aqueous solutions on the basis of the charge interactions between the protonated cationic 2VP and anionic NaSS units. With an increase in pH value, the interaction was weakened because of the deprotonation of the 2VP units, thus reducing the UCST. At high [NaCl], the electrostatic interactions among the polymers were weakened because of the screening effect, and again, the UCST was reduced. With an increase in polymer concentration, the intra- and interpolymer interactions increased because of some entanglement, and the UCST consequently increased. Electrostatic interactions among the polymer chains with high molecular weight occurred easier than those among the low-molecular-weight polymer chains, which increased the UCST. The UCST also increased when deuterium oxide was used instead of hydrogen oxide, which was due to the isotopic effect. Hence, the UCST of P(2VP/NaSS)n can be adjusted according to the desired application.

Aqueous Synthesis of Upper Critical Solution Temperature and Lower Critical Solution Temperature Copolymers through Combination of Hydrogen-Donors and Hydrogen-Acceptors.

The synthesis of thermo-responsive polymers from non-responsive and water-soluble monomers has great practical advantages but significant challenges. Herein, the authors report a novel aqueous copolymerization strategy to prepare polymers with tunable upper critical solution temperature (UCST) or lower critical solution temperature (LCST) from non-responsive monomers. Acrylic acid (AAc), N-vinylpyrrolidone (NVP), and acrylamide (AAm) are copolymerized in water, yielding copolymers with UCST behavior. Interestingly, by simply replacing AAm with its methylated homologue, dimethyl acrylamide (DMA), the thermo-responsiveness of the copolymers is converted into LCST-type. The cloud points of the copolymers can be tuned rationally with their monomer ratios and the condition of the solvent. The UCST property of the poly(AAc-NVP-AAm) comes from the AAc-AAm and AAc-NVP hydrogen-bonds, while the LCST property of poly(AAc-NVP-DMA) originates from the hydrophobic aggregation of AAc-NVP complex and DMA, as indicated by temperature-dependent 1 H NMR and dynamic light scattering.

Oxazoline-methacrylate graft-copolymers with upper critical solution temperature behaviour in Yubase oil

Thermoresponsive behaviour of 2-oxazoline based graft copolymers has been studied in non-aqueous solutions.

Thermo-Responsive Behavior of Mixed Aqueous Solution of Hydrophilic Polymer with Pendant Phosphorylcholine Group and Poly(Acrylic Acid).

A mixed aqueous solution of hydrophilic poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) and poly(acrylic acid) (PAAc) becomes cloudy under acidic conditions at room temperature. The pendant carboxylic acid groups in PAAc form hydrogen bonds with the ester and phosphate groups in PMPC. While the polymers aggregate under acidic conditions, neither one associate under basic conditions because of the deprotonation of the pendant carboxy groups in PAAc. We observed that the interpolymer complex formed from PMPC, and PAAc was dissociated in aqueous solutions with increasing temperature, which is an upper critical solution temperature behavior. With increasing temperature, the molecular motion increased to dissociate the interpolymer complex. The phase transition temperature increased with increasing polymer and salt concentrations, and with decreasing pH.

Sulfobetaine-based polydisulfides with tunable upper critical solution temperature (UCST) in water alcohols mixture, depolymerization kinetics and surface wettability

HypothesisSynthesis of a new family of polymers having a polydisulfide structure can be conducted from sulfobetaine-based derivative of natural (R)-lipoic acid. A polydisulfide backbone of polymer can be depolymerized by response to external stimuli and sulfobetaine pendant groups ensure the upper critical solution temperature (UCST) behaviour temperatures that can be modulated according to the nature of the solvent and concentration. ExperimentsSulfobetaine-bearing polydisulfides were synthesized from dithiolane derivatives and then characterized. UCST behavior of the polymers in water and in mixtures containing different alcohols (methanol, ethanol, isopropanol) was investigated. The regeneration of monomers from the polymers in response to external stimuli was examined using UV–vis and circular dichroism (CD) spectroscopy. Tunable surface wettability were shown on the grafted polymers. FindingsDecreasing polarity and/or increasing alcohol percentage in the water mixtures induced an increase in the cloud points of the polymers in the solutions. Thermoresponsive behaviour were repeatable and fully reversible with negligible hysteresis from aggregate to unimer state. The regeneration of monomers by depolymerization was tunable by temperature and sunlight. A thickness dependence on surface wettability was observed on wafers covalently modified with polydisulfides. This is the first report of sulfobetaine-based polydisulfides showing tunable UCST behavior and surface wettability.

Highly Bidirectional Bendable Actuator Engineered by LCST-UCST Bilayer Hydrogel with Enhanced Interface.

Thermoresponsive hydrogel-based actuators are highly important for fundamental research and industrial applications, while the preparation of temperature-driven bilayer hydrogel actuators with rapid response to bend and recover properties remains a challenge. To date, most temperature-driven bilayer hydrogel actuators are based on polymers only with a lower critical solution temperature (LCST) or with an upper critical solution temperature (UCST), which need more time to bend and recover just in a small range of bending angle. Herein, we propose a new strategy to design and synthesize a fully temperature-driven bilayer hydrogel actuator, which consists of a poly(N-acryloyl glycinamide) (NAGA) layer with a UCST-type volume phase change and a poly(N-isopropyl acrylamide) (NIPAM)-Laponite nanocomposite layer with an LCST-type volume phase change. Due to the complementary UCST and LCST behavior of the two selected polymers, both layers have opposite thermoresponsive swelling and shrinkage properties at low and high temperatures; this imbues the hydrogel actuator with rapid thermoresponsive bending and recovery ability, as well as a large bending angle. In addition, the incorporation of Laponite nanosheets in PNIPAM layer not only improves the mechanical property of actuators but also provides the excellent bonding ability of the two-layer interface, which prevents delamination caused by excessive local stress on the interface during the bending process. Thanks to high-performance behavior, the actuator can act as an effective and sensitive actuator, such as a gripper to capture, transport, and release an object, or as an electrical circuit switch to turn on and off a light-emitting diode (LED). Overall, such hydrogel actuator may provide new insights for the design and fabrication of artificial intelligence materials.