Thermoresponsive Phase Transition Research Articles

Thermoresponsive Gelation and Phase Transition of PEG/Cation Random Terpolymer Micelles in Water in the Presence of Salts

Thermoresponsive Gelation and Phase Transition of PEG/Cation Random Terpolymer Micelles in Water in the Presence of Salts

UCST-Type Thermoresponsive Sol-Gel Transition Triblock Copolymer Containing Zwitterionic Polymer Blocks.

Thermoresponsive sol-gel transition polymers are of significant interest because of their fascinating biomedical applications, including as drug reservoirs for drug delivery systems and scaffolds for tissue engineering. Although extensive research has been conducted on lower critical solution temperature (LCST)-type sol-gel transition polymers, there have been few reports on upper critical solution temperature (UCST)-type sol-gel transition polymers. In this study, we designed an ABA-type triblock copolymer composed of a poly(ethylene glycol) (PEG) block and zwitterionic polymer blocks that exhibit UCST-type thermoresponsive phase transitions. A sulfobetaine (SB) monomer with both ammonium and sulfonate (-SO3) groups in its side chain or a sulfabetaine (SaB) monomer with both ammonium and sulfate (-OSO3) groups in its side chain was polymerized from both ends of the PEG block via reversible addition-fragmentation chain-transfer (RAFT) polymerization to obtain PSB-PEG-PSB and PSaB-PEG-PSaB triblock copolymers, respectively. Although an aqueous solution containing the PSB-PEG-PSB triblock copolymer showed an increase in viscosity upon cooling, it did not undergo a sol-to-gel transition. In contrast, a sol-to-gel transition was observed when a phosphate-buffered saline containing PSaB-PEG-PSaB was cooled from 80 °C to 25 °C. The PSaB blocks with -OSO3 groups exhibited a stronger dipole-dipole interaction than conventional SB with -SO3 groups, leading to intermolecular association and the formation of a gel network composed of PSaB assemblies bridged with PEG. The fascinating UCST-type thermoresponsive sol-gel transition properties of the PSaB-PEG-PSaB triblock copolymer suggest that it can provide a useful platform for designing smart biomaterials, such as drug delivery reservoirs and cell culture scaffolds.

Dynamic fluorescence imaging and controllable capture/release of guests based on thermo-responsive perylene-cyclodextrin conjugates

In view of the fact that multivalent intermolecular noncovalent interactions are the main elements for the formation of phase separation, supramolecular entities are a type of multivalent system. However, the phase separation system based on single supramolecular molecules was limited. In this paper, two permethyl-β-cyclodextrin modified perylene monoamide derivatives (PMI-B-CD and PMI-N-CD) with modification of benzene and naphthalene groups at the bay position of perylene backbone were synthesized. Of interest, PMI-B-CD and PMI-N-CD showed a LCST effect due to a self-inclusion interaction between PMCD and the benzene or naphthalene groups in the bay position of perylene monoamide backbone. Dynamic confocal fluorescence imaging of PMI-B-CD and PMI-N-CD showed thermo-responsive phase separation process. It is surprised that PMI-B-CD and PMI-N-CD achieved thermo-responsive capture and release of aromatic guests. Dynamic phase separation and controllable capture and release of guests with thermo-responsive phase transition process are found, which opens a novel supramolecular principle of liquid-liquid transition.

Synthesis of Poly[N‐(2‐((3‐Morpholino‐3‐Oxopropyl)Thio)Ethyl)Methacrylamide]: A New Thermoresponsive Polymer with Tunable LCST‐ and UCST‐Type Phase Transition in Aqueous and Alcoholic Solutions

AbstractA novel monomer, N‐(2‐((3‐morpholine‐3‐isopropyl)thio)ethyl)methacrylamide (MTMA), is synthesized and polymerized by reversible addition‐fragmentation chain transfer (RAFT) polymerization to give a thermoresponsive polymer poly[N‐(2‐((3‐morpholino‐3‐oxopropyl)thio)ethyl)methacrylamide] (PMTMA). PMTMA exhibits reversible thermoresponsive phase transitions of the lower critical solution temperature (LCST) type in water and the upper critical solution temperature (UCST) type in ethanol and methanol. The degree of polymerization and concentration of PMTMA, and solvent type have a significant influence on the transition temperature. PMTMA shows complicated thermoresponse in water–alcohol mixtures. In water–ethanol mixtures, the phase diagram of PMTMA can be divided into three regions according to ethanol volume percentages, φ: 0 ≤ φ < 15% for an LCST region; 15% ≤ φ < 91.5% for a complete dissolution region; 91.5% ≤ φ ≤ 100% for a UCST region. At high water content, the LCST increases with increasing ethanol content; and at high ethanol content, the UCST decreases with increasing water content. In water–methanol mixtures, PMTMA shows more complex thermoresponse. In the range of 0–50 °C, the phase diagram can be divided into five regions, depending on the methanol volume percentages φ: 0 ≤ φ < 15% for LCST region; 15% ≤ φ < 25% for immiscible region; 25% ≤ φ < 85% for UCST region; 85% ≤ φ < 95% for fully dissolved region; 95% ≤ φ ≤ 100% for another UCST region.

Phase Transition Behaviors of Poly(N-isopropylacrylamide) Nanogels with Different Compositions Induced by (−)-Epigallocatechin-3-gallate and Ethyl Gallate

Phase transition behaviors of poly(N-isopropylacrylamide) nanogels with different compositions induced by (−)-epigallocatechin-3-gallate (EGCG) and ethyl gallate (EG) has been investigated systematically. Monodisperse poly(N-isopropylacrylamide-co-N-hydroxymethyl acrylamide) (P(NIPAM-co-NMAM)) and poly(N-isopropylacrylamide-co-2-hydroxyethyl methacrylate) (P(NIPAM-co-HEMA)) nanogels with different feeding monomer ratios were prepared by emulsion polymerization. P(NIPAM-co-NMAM) nanogels exhibit rapid isothermal phase transition behavior in EGCG solutions with low concentration (10−3 mol/L) in less than 10 minutes. The thermosensitive phase transition behaviors of nanogels are affected not only by the copolymerized monomers but also by the concentrations of EGCG and EG in aqueous solutions. Nanogels remain in a shrunken state and do not exhibit thermosensitive phase transition behaviors in EGCG solutions (≥5 mmol/L), whereas they display thermo-responsive phase transition behaviors in EG solutions. The volume phase transition temperature (VPTT) shifts to lower temperatures with increasing EG concentration. The diameters of P(NIPAM-co-NMAM) nanogels decrease with increasing EG concentration at temperatures between 29 and 33 °C. In contrast, the diameters of P(NIPAM-co-HEMA) nanogels increase with increasing EGCG concentration at temperatures between 37 and 45 °C. The results demonstrate the potential of nanogels for simple detection of EG and EGCG concentrations in aqueous solutions over a wide temperature range, and EGCG can serve as a signal for the burst-release of drugs from the P(NIPAM-co-NMAM)-based carriers at physiological temperature.

Thermo-Sensitive Poly (N-isopropylacrylamide-co-polyacrylamide) Hydrogel for pH-Responsive Therapeutic Delivery.

Stimuli-response polymeric nanoparticles have emerged as a carrier system for various types of therapeutic delivery. In this study, we prepared a dual pH- and thermo-sensitive copolymer hydrogel (HG) system (PNIPAm-co-PAAm HG), using N-isopropyl acrylamide (NIPAm) and acrylamide (AAm) as comonomers. The synthesized PNIPAm-co-PAAm HG was characterized using various instrumental characterizations. Moreover, the PNIPAm-co-PAAm HG’s thermoresponsive phase transition behavior was investigated, and the results showed that the prepared HG responds to temperature changes. In vitro drug loading and release behavior of PNIPAm-co-PAAm HG was investigated using Curcumin (Cur) as the model cargo under different pH and temperature conditions. The PNIPAm-co-PAAm HG showed pH and temperature-responsive drug release behavior and demonstrated about 65% Cur loading efficiency. A nearly complete release of the loaded Cur occurred from the PNIPAm-co-PAAm HG over 4 h at pH 5.5 and 40 °C. The cytotoxicity study was performed on a liver cancer cell line (HepG2 cells), which revealed that the prepared PNIPAm-co-PAAm HG showed good biocompatibility, suggesting that it could be applied as a drug delivery carrier. Moreover, the in vitro cytocompatibility test (MTT assay) results revealed that the PNIPAm-co-PAAm HG is biocompatible. Therefore, the PNIPAm-co-PAAm HG has the potential to be useful in the delivery of drugs in solid tumor-targeted therapy.

Mechanism insights in controlling host–guest (de)complexation by thermoresponsive polymer phase transitions

The hydrophobic interactions involved in phase separation of LCST polymers are the critical factor inducing the BBox release from the BBox/naphthalene while the host-guest complexes remain stable during phase separation of UCST polymers upon cooling.

Reducing Thermal Damage to Adjacent Normal Tissue with Dual Thermo-Responsive Polymer Via Thermo-Induced Phase Transition for Precise Photothermal Theranosis

Reducing Thermal Damage to Adjacent Normal Tissue with Dual Thermo-Responsive Polymer Via Thermo-Induced Phase Transition for Precise Photothermal Theranosis

Rational design of hydrogen bonds for driving thermo-responsive phase transition and assembly behavior of block copolymer in water

Hydrogen bonding interactions were intensified in the present study by adjusting the chain architectures, which provided a sufficient driving force for UCST phase transition in pure water.

Effect of the macromolecular architecture on the thermoresponsive behavior of poly(N-isopropylacrylamide) in copolymers with poly(N,N-dimethylacrylamide) in aqueous solutions: Block vs random copolymers

Three samples from each type of poly(N-isopropylacrylamide)-block-poly(N,N-dimethylacrylamide) (PNIPAM-b-PDMA) block copolymers and poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) (P(NIPAM-co-DMA)) random copolymers with similar chemical composition were synthesized by RAFT polymerization. The effects of DMA on the thermoresponse of its two kinds of copolymers with NIPAM were comparatively investigated by turbidity analysis, variable-temperature 1H NMR and dynamic light scattering with PNIPAM homopolymer as a control. It was discovered that the phase transition temperature, the temperature response window and the hysteresis values of the PNIPAM-b-PDMA and P(NIPAM-co-DMA) counterpart were significantly different. In particular, the temperature response window, which represents the sensitivity of response, is smaller for random copolymers than that of block copolymers in aqueous solution, indicating that the temperature response of random copolymers is more sensitive than that of block copolymers. The possible reasons leading to different thermo-responsive phase transition characteristics between block copolymers and random copolymers are discussed, and the formation of different hydrophobic structures with the temperature increasing is ascribed.

Fabrication of thermoresponsive metal-organic nanotube sponge and its application on the adsorption of endocrine-disrupting compounds and pharmaceuticals/personal care products: Experiment and molecular simulation study.

Thermoresponsive metal-organic nanotube modified (MONT-pNIPAM, pNIPAM=poly N-isopropylacrylamide) sponge was synthesized using the dip-coating method and served as an adsorbent for endocrine-disrupting compounds (EDCs) and pharmaceuticals/personal care products (PPCPs) removal. The material was characterized using Fourier transform infrared spectroscopy, scanning electron microscopy, X-ray diffraction, and N2 sorption-desorption. Nonlinear regression-based equations were derived to optimize pH and ionic strength during process. Though thermoresponsive polymer phase transition between dissolve and aggregate, realizing the adsorption tunnel "ON-OFF" under the temperature control. Adsorption kinetics and isotherms were investigated on the basis of a static experiment. The pseudo-second-order kinetic model and the Langmuir isotherm were fitted well to characterize adsorption. At an initial concentration of 50mgL-1, maximum adsorption capacity were 128mg/g, 184mg/g and partition coefficient were 1.09mgg-1 μM-1, 1.13mgg-1 μM-1 for dibutyl phthalate (DBP) and parachlorometaxylenol (PCMX), respectively. The density-functional theory (DFT) was applied to calculate the interaction energy and investigate the possible mechanism. Combining the experimental data with theoretical calculation, results demonstrated that the MONT-pNIPAM sponge was a highly efficient adsorbent material that was suitable for the removal of EDCs/PPCPs from water.

Effect of Alkyl Chain Length of Acylated α‐Cyclodextrin‐Threaded Polyrotaxanes on Thermoresponsive Phase Transition Behavior

AbstractThe temperature‐dependent phase transition behavior of acetylated polyrotaxanes (PRXs) consisting of acylated α‐cyclodextrins threaded onto a poly(ethylene glycol) chain in an aqueous solution is investigated. Acetyl (Ac), propionyl (Pr), and butyryl (Bu) group‐modified PRXs with different degrees of substitution are synthesized to elucidate the effect of the alkyl chain length of the acyl groups on temperature responsivity. Ac‐PRXs, Pr‐PRXs, and Bu‐PRXs are dissolved in water and exhibit temperature‐dependent transmittance changes accompanied by coacervate formation. However, the temperature responsivity of acylated PRXs is seen in limited degree of substitution range (≈10%). The maximum degree of substitution to show temperature responsivity of acylated PRXs decreases with increasing alkyl chain length of the acyl groups. Transmittance measurements of acylated PRXs in the presence of urea reveal that the alkyl chain length of the acyl groups determines the predominant force involved in the temperature‐induced phase transition. During the temperature‐induced phase transition of Pr‐PRXs and Bu‐PRXs, hydrophobic interactions are predominant; however, hydrogen bond formation may occur in Ac‐PRXs. These fundamental findings related to acylated PRXs will facilitate the application of PRXs as thermoresponsive supramolecular materials.

Combinatorial discovery of small-molecule 1,2,3-triazolium ionic liquids exhibiting lower critical solution temperature phase transition

Both lower and upper critical solution temperature (LCST and UCST) systems are two typical phase behaviors of thermoresponsive materials with solvents, in which LCST is far less common than UCST. Recent studies on ionic liquids carrying LCST phase transitions have predominantly focused on quaternary ammonium- and phosphonium-based ionic salts. Based on the 1,2,3-triazole core structure assemblable by azide-alkyne cycloaddition click reaction, this work reports the combinatorial synthesis of 1,3,4-trialkylated 1,2,3-triazolium ionic liquids in three libraries with a total of 160 ionic liquids and demonstrates, for the first time, their values in temperature-switchable phase transition with water. In this work, the successful discovery of a new thermoresponsive ionic liquid b26, based on the structure-and-phase separation study of b8 and b9, perfectly exemplified the true value of the tunability of ionic liquid fine structures. For all 160 ionic liquids synthesized, 155 are liquid at room temperature and 22 room-temperature ionic liquids were found to exhibit thermoresponsive phase transitions having low Tc values in water. To the best of our knowledge, this comprehensive study is the first report of small-molecule 1,2,3-triazolium ionic liquids that exhibit LCST property in water.

Distinct Cation-Anion Interactions in the UCST and LCST Behavior of Polyelectrolyte Complex Aqueous Solutions.

Polyelectrolyte complexes (PECs) are recently observed to possess diversified thermoresponsive phase transition behaviors in aqueous solutions. Herein, by adjusting the initial polymer concentrations (Cpi) of poly(styrenesulfonate) (PSS)/poly(diallyldimethylammonium) (PDADMA) PEC in the same saline solution, in addition to previously reported lower critical solution temperature (LCST), we experimentally observed the upper critical solution temperature (UCST)-type phase transition behavior of PSS/PDADMA PECs at a lower polymer concentration. As elucidated by temperature-dependent Raman spectroscopy and two-dimensional correlation analysis, at temperatures lower than UCST, more hydrophobic polyelectrolyte chains lead to a high proportion of contact ion pairs (CIPs), contributing to UCST-type solid-liquid phase transition; however, at higher concentrations of PEC, the less hydrophobic polyelectrolyte chains correspond to a higher proportion of solvent-separated ion pairs (SIPs), which enables the occurrence of LCST-type liquid-liquid phase transition. With the spectroscopic indicator of CIPs/SIPs peak ratio and monitoring the hydration state of polymer chains, the complex interplays of PSS/PDADMA PECs are hereby interpreted at the molecular level, which lays the mechanistic foundation for designing other thermoresponsive PEC assemblies.

Thermo-Responsive MOF/Polymer Composites for Temperature-Mediated Water Capture and Release.

We report an in situ polymerization strategy to incorporate a thermo-responsive polymer, poly(N-isopropylacrylamide) (PNIPAM), with controlled loadings into the cavity of a mesoporous metal-organic framework (MOF), MIL-101(Cr). The resulting MOF/polymer composites exhibit an unprecedented temperature-triggered water capture and release behavior originating from the thermo-responsive phase transition of the PNIPAM component. This result sheds light on the development of stimuli-responsive porous adsorbent materials for water capture and heat transfer applications under relatively mild operating conditions.

Observation of Unusual Thermoresponsive Volume Phase Transition Behavior of Cubic Poly(N-isopropylacrylamide) Microgels.

Here, we report the observation of an unusual thermoresponsive volume phase transition behavior of cubic poly(N-isopropylacrylamide) (PNIPAM) microgels. Cubic PNIPAM microgels with a mean edge size of 125 ± 41 nm were synthesized via electrochemical-initiated radical polymerization with a photovoltaic cell as power supply. In turbidity and laser light scattering studies on dilute aqueous dispersions of these cubic microgels, both the light attenuation and hydrodynamic radius variations with temperature reveal an additional transition at about 25.0 °C, besides the widely reported volume phase transition at the PNIPAM LCST that is typically found for (quasi-)spherical microgels. This unusual thermoresponsive volume phase transition behavior of the cubic microgels can be elucidated by using a core-corona model, with the contribution from each part varying at different temperatures. The finding is also checked by thermal analysis.

Combined Theoretical and Computational Approach for Calculating Sequence-specific Phase Diagrams of Thermoresponsive Intrinsically Disordered Homopolypeptides

Peptide-based homopolymers comprise of multiple repeats of short peptide motifs. These intrinsically disordered homopolypeptides undergo different types of responsive phase transitions. Of particular interest are homopolypeptides that undergo thermoresponsive phase transitions whereby dense condensates are formed in response to increases above or decreases below sequence-specific critical solution temperatures. We recently developed a sequence design algorithm that combines heuristics derived from simplified all-atom simulations with Monte Carlo sampling and a sequence generating genetic algorithm [1]. This design approach can be deployed for rapid generation of hundreds to thousands of novel sequences that are predicted to have the desired thermoresponsive phase behavior. However, the most rigorous way of knowing if the designed sequence has the desired thermoresponsive features is to have access to the full temperature-dependent phase diagram. Here, we deploy a novel approach that combines computation with theory to enable the calculation of desired phase diagrams. To achieve this, we adapt, refine, and deploy the Gaussian cluster theory of Raos and Allegra [2] that was developed to model coil-to-globule transitions and phase transitions of homopolymers as a function of solution temperature. We extract temperature-dependent two- and three-body interaction coefficients and the predicted theta temperatures from all-atom simulations of interactions among the repeating units that make up homopolypeptides. Using these interaction coefficients as inputs, we use the Gaussian cluster theory to calculate sequence-specific phase diagrams for homopolypeptides. We showcase the joint computational and theoretical approach by applying it to calculate phase diagrams for homopolypeptides that have different types of thermoresponsive phase behaviors.

Noncovalent and Dynamic Covalent Chemistry Strategies for Driving Thermoresponsive Phase Transition with Multistimuli and Controlled Encapsulation/Release.

We report the development of multiresponsive thermally sensitive polymers through both supramolecular and reversible covalent strategies as well as their use in controlled encapsulation and release. Novel acylhydrazone-based dynamic covalent polymers displaying lower critical solution temperature (LCST) or upper critical solution temperature (UCST) were synthesized. A remarkable control over thermal phase transition can be tuned through multimodes, such as anions, cations, solvent, pH, and competing components. In particular, anion recognition allowed disassembly and thus led to a significant decrease of UCST in dimethyl sulfoxide, and the combination of anion and solvent effects offered additional handle for control. Moreover, the use of anions, cations, as well as pH change was employed for the modulation of LCST-type polymer in water. Furthermore, switching on/off thermoresponsiveness was readily achieved by dynamic covalent exchange. Mechanistic studies also shed light on stimuli-induced changes in aggregation behaviors. Finally, thermally controlled encapsulation and release of hydrophobic and hydrophilic dyes were realized with great repeatability and reversibility, respectively, showing potential in delivery and sensing. The results and strategies described should provide opportunities for many aspects, including dynamic assemblies, complex systems, and adaptive materials.

Supramolecular Polymer Network-Mediated Structural Phase Transitions within Polymeric Micelles in Aliphatic Alcohols.

Self-complementary supramolecular polymers (SCSPs), an efficient combination of sextuple hydrogen-bonded dimer moieties and a temperature-responsive polymer, can promote the construction of stable supramolecular polymer networks (SPNs) that enable the formation of well-defined nanospherical micelles in aliphatic alcohols. These micelles undergo tailorable, thermoresponsive phase transitions at the upper critical solution temperature (UCST) and have a desirable spherical morphology and size ranges, thus, are potential candidates for applications in interfacial engineering and biomedical fields. Moreover, concentration-dependent UCST measurements and variable-temperature experiments indicated that the hydrogen-bonded complexes are strong enough to form stable intermolecularly entangled SPNs within the micelles, even above the UCST or at low concentrations in solution, which enables the micelles to undergo reversible temperature-dependent conformational changes between insoluble and soluble globules without significant changes in particle size or size distribution. Thus, this newly discovered system offers a new approach toward the development of next-generation temperature-responsive SCSPs with the desired structural stability that undergoes UCST transitions.

Single component Pluronic F127-lipoic acid hydrogels with self-healing and multi-responsive properties

Herein, Pluronic F127 (PEO99-PPO65-PEO99) end functionalized with α-lipoic acid (LA) (F127-LA) was synthesized and used for preparation of “single-component, multi-responsive” hydrogels through the photo cross-linking of LA components. The F127-LA hydrogels not only possessed thermo- and reduction- double responsiveness, but also demonstrated self-healing properties under UV irradiation due to the existence of dynamic disulfide bonds. The rheological and mechanical properties of the hydrogels can be adjusted by their concentration. The F127-LA hydrogels presented a swelling ratio decrease from 25 °C to 37 °C due to a lower critical solution temperature (LCST)-type thermo-responsive volume phase transition. The bovine serum albumin (BSA) was loaded into F127-LA hydrogels, and their drug release behavior can be regulated by surrounding temperature and reducing agent concentration. The volume shrinkage of the hydrogels promoted the sustained release of BSA above volume phase transition temperature. Cytocompatibility assay of L929 mouse fibroblasts showed that cellular metabolic activity were merely affected by F127-LA, even at concentrations up to 1000 mg L−1. This study thus provided a very promising route for the preparation of multifunctional hydrogels.