2,6‐Diaminopyridine and Acrylamide‐Based Copolymers with Upper Critical Solution Temperature‐type Behavior in Aqueous Solution

A novel copolymer based on supramolecular motif 2,6‐diaminopyridine and water‐soluble acrylamide, poly[N‐(6‐acetamidopyridin‐2‐yl) acrylamide‐co‐acrylamide], was synthesized via reversible addition–fragmentation chain transfer (RAFT) polymerization with various monomer compositions. The thermoresponsive behavior of the copolymers was studied by turbidimetry and dynamic light scattering (DLS). The obtained copolymers showed an upper critical solution temperature (UCST)‐type phase transition behavior in water and electrolyte solution. The phase transition temperature was found to increase with decreasing amount of acrylamide in the copolymer and increasing concentration of the solution. Furthermore, the phase transition temperature varied in aqueous solutions of electrolytes according to the nature and concentration of the electrolyte in accordance with the Hoffmeister series. A dramatic solvent isotope effect on the transition temperature was observed in this study, as the transition temperature was almost 10–12 °C higher in D₂O than in H₂O at the same concentration and acrylamide composition. The size of the aggregates below the transition temperature was larger in D₂O compared to that in H₂O that can be explained by deuterium isotope effect. The thermoresponsive behavior of the copolymers was also investigated in different cell medium and found to be exhibited UCST‐type phase transition behavior in different cell medium. Such behavior of the copolymers can be useful in many applications including biomedical, microfluidics, optical materials, and in drug delivery. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 2064–2073     

A Synthetic,Transiently Thermoresponsive Homopolymer with UCST Behaviour within a Physiologically Relevant Window

Interactive materials that can respond to a trigger by changing their morphology, but that can also gradually degrade into a fully soluble state, are attractive building blocks for the next generation of biomaterials. Herein, we design such transiently responsive polymers that exhibit UCST behaviour while gradually losing this property in response to a hydrolysis reaction in the polymer side chains. The polymers operate within a physiologically relevant window in terms of temperature, pH, and ionic strength. Whereas such behaviour has been reported earlier for LCST systems, it is at present unexplored for UCST polymers. Furthermore, we demonstrate that, in contrast to LCST polymers, in aqueous medium the UCST polymer forms a coacervate phase below the UCST, which can entrap a hydrophilic model protein, as well as a hydrophobic dye. Because of their non‐toxicity, we also provide in vivo proof of concept of the use of this coacervate as a protein depot, in view of sustained‐release applications.     

Visualizing phase transition of upper critical solution temperature (UCST) polymers with AIE

The stimuli-responsive polymers with upper critical solution temperatures(UCST) are highly attractive for drug delivery applications. However, the phase transition process of UCST polymer is usually characterized by turbidity measurement and electron microscopy, which are significantly restricted by low sensitivity and static observation. In contrary, the fluorescence technique has significant advantages in terms of high sensitivity, easy operation, and dynamic observation. However, the conventional fluorophores suffer from the drawbacks of aggregation-caused quenching(ACQ) after being encapsulated by UCST polymers, which are not suitable for direct visualization of the phase transition process. To tackle this challenge, we herein developed a series of UCST polymers based on polyacrylamides decorated with bile acid and aggregation-induced emission(AIE)-active tetraphenylethene(TPE) groups, which can be used for direct fluorescence monitoring of the phase transition process. Moreover, the AIE-active UCST polymers can serve as drug carriers, which can not only monitor the drug release process under thermal stimuli, but also verify the drug release by fluorescence recovery after thermal stimuli. It is expected that the AIE-active UCST polymers with self-monitoring ability are promising for biomedical applications.     

Tunable UCST thermoresponsive copolymers based on natural glycyrrhetinic acid

Water-soluble thermoresponsive polymers present either upper critical solution temperature(UCST) or lower critical solution tempe rature(LCST) depending on the location of their miscibility range with water at high temperatures or at low temperatures.Compared with LCST polymers,the water-soluble UCST polymers are still less explored until now.In this work three copolymers of P(AAm-co-GAA) were synthesized by copolymerizing two acrylamide monomers,acrylamide(AAm) and acrylamide functionalized with natural glycyrrhetinic acid(GAA),using reversible addition-fragmentation chain transfer(RAFT) polymerization.These copolymers exhibited the typical UCST thermoresponsive behavior,and their phase transition temperatures could be easily tuned to around 37℃ for potential biological applications.Moreover,the UCST of P(AAm-co-GAA) can be adjusted not only by the content of glycyrrhetinic acid(GA) and polymer concentrations,but also by the host-guest interactions between GA and cyclodextrins(β-and γ-CD).The suitable value of UCST and the biocompatible nature of GA and CDs may endow these copolymers with practical applications in biomedical chemistry.     

Liquid-liquid equilibria of polymer solutions: Applicability of extended Redlich-Kister expansion

We developed a simple and improved expression for the Helmholtz energy of mixing which uses a Taylor series of an exponential function based on extending the Redlich-Kister expansion. This model incorporates the chain-length dependence of polymers and specific interactions such as hydrogen bonds. The proposed model can accurately predict most phase diagrams of various binary polymer solutions including upper critical solution temperature (UCST), lower critical solution temperature (LSCT), both UCST and LCST, and closed miscibility loops. Our model fits experimental data of the complex phase behavior of polymer solutions well.     

Unusual phase behavior in mixtures of poly(ethylene oxide) and ethyl alcohol

Poly(ethylene oxide) (PEO), soluble in both aqueous and organic solvents, is one of the most intriguing polymers. PEO solution properties have been extensively studied for decades; however, many of the studies have focused on specific properties, such as clustering, of PEO in aqueous solutions, and the behavior of PEO in organic solvents has not been adequately explored. The results presented here demonstrate that PEO crystallizes into a lamellar structure in ethyl alcohol after the mixture is quenched to room temperature from a temperature above the crystal melting point. Above the melting temperature, PEO completely dissolves in ethyl alcohol, and the mixture exhibits regular polymer solution thermodynamic behavior with an upper critical solution temperature (UCST) phase diagram. Remarkably, the UCST phase boundary is significantly below the melting temperature, and this indicates that the system undergoes a crystallization process before the phase separation can occur upon cooling and, therefore, possesses an unusual phase transition. The phase transition from the crystalline state to the miscible solution state is reversible upon heating or cooling and can be induced by the addition of a small amount of water. © 2005 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 44: 557–564, 2006     

Design of a Tunable Self‐Oscillating Polymer with Ureido and Ru(bpy)3 Moieties

An upper critical solution temperature (UCST)‐type self‐oscillating polymer was designed that exhibited rhythmic soluble–insoluble changes induced by the Belousov–Zhabotinsky (BZ) reaction. The target polymers were prepared by conjugating Ru(bpy)₃, a catalyst for the BZ reaction, to ureido‐containing poly(allylamine‐co‐allylurea) (PAU) copolymers. The Ru(bpy)₃‐conjugated PAUs exhibited a UCST‐type phase‐transition behavior, and the solubility of the polymer changed in response to the alternation in the valency of Ru(bpy)₃. The ureido content influences the temperature range of self‐oscillation, and the oscillation occurred at higher temperatures than conventional LCST‐type self‐oscillating polymers. Furthermore, the self‐oscillating behavior of the Ru‐PAU could be regulated by addition of urea, which is a unique tuning strategy. We envision that novel self‐oscillating polymers with widely tunable soluble‐insoluble behaviors can be rationally designed based these UCST‐type polymers.     

Upper Critical Solution Temperature-Type Responsive Cyclodextrins with Characteristic Inclusion Abilities

Water-soluble and thermoresponsive macrocycles with stable inclusion toward guests are highly valuable to construct stimuli-responsive supramolecular materials for versatile applications. Here, we develop such macrocycles – ureido-substituted cyclodextrins (CDs) which exhibit unprecedented upper critical solution temperature (UCST) behavior in aqueous media. These novel CD derivatives showed good solubility in water at elevated temperature, but collapsed from water to form large coacervates upon cooling to low temperature. Their cloud points are greatly dependent on concentration and can be mediated through oxidation and chelation with silver ions. Significantly, the amphiphilicity of these CD derivatives is supportive to host-guest binding, which affords them inclusion abilities to guest dyes. The inclusion complexation remained nearly intact during thermally induced phase transitions, which is in contrast to the switchable inclusion behavior of lower critical solution temperature (LCST)-type CDs. Moreover, ureido-substituted CDs were exploited to co-encapsulate a pair of guest dyes whose fluorescence resonance energy transfer process can be switched by the UCST phase transition. We therefore believe these novel thermoresponsive CDs may form a new strategy for developing smart macrocycles and allow for exploring smart supramolecular materials.     

Tuning the thermochromism of water-soluble poly(3-thiopheneacetic acid) conjugated polymer by complexation with zwitterionic polymer

The spectral properties and phase behavior of the complexes of the water-soluble poly(3-thiopheneacetic acid) (P3TAA) conjugated polymer with zwitterionic 3-dimethyl(methacryloyloxyethyl) ammonium propane sulfone (PDMAPS) polymer were explored. A dramatic change in both electronic spectra and upper critical solution temperature (UCST) of P3TAA-PDMAPS complex solution was observed depending on the molar ratio of P3TAA and PDMAPS, suggesting that a conformational transition due to complexation occurred. The UV–vis λ_max of P3TAA-PDMAPS complex solutions was changed dramatically in a narrow temperature range around a UCST and found to be varied over approximately a 40 nm range by the temperature change of about 20 °C.     

A new thermo‐responsive block copolymer with tunable upper critical solution temperature and lower critical solution temperature in the alcohol/water mixture

The multi‐thermo‐responsive block copolymer of poly[2‐(2‐methoxyethoxy)ethyl methacrylate]‐block‐poly[N‐(4‐vinylbenzyl)‐N,N‐diethylamine] (PMEO₂MA‐b‐PVEA) displaying phase transition at both the lower critical solution temperature (LCST) and the upper critical solution temperature (UCST) in the alcohol/water mixture is synthesized by reversible addition‐fragmentation chain transfer polymerization. The poly[2‐(2‐methoxyethoxy)ethyl methacrylate] (PMEO₂MA) block exhibits the UCST phase transition in alcohol and the LCST phase transition in water, while the poly[N‐(4‐vinylbenzyl)‐N,N‐diethylamine] (PVEA) block shows the UCST phase transition in isopropanol and the LCST phase transition in the alcohol/water mixture. Both the polymer molecular weight and the co‐solvent/nonsolvent exert great influence on the LCST or UCST of the block copolymer. By adjusting the solvent character including the water content and the temperature, the block copolymer undergoes multiphase transition at LCST or UCST, and various block copolymer morphologies including inverted micelles, core‐corona micelles, and corona‐collapsed micelles are prepared. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 4399–4412     

UCST‐type phase transition driven by protein‐derived polypeptide employing gelatin and chitosan

Here, we describe the thermosensitive reversible phase transition behaviors of polyelectrolyte complex composed of gelatin and chitosan (G/C complex). An aqueous dispersion of the G/C complexes showed a clear upper critical solution temperature (UCST) at around 30°C. The thermosensitive phase transition behavior showed excellent reversibility and large thermal hysteresis as a usual phenomenon based on the intra‐ and inter‐molecular interaction change. A high correlation was observed between the UCST of the G/C complex and the helix‐melting temperature of gelatin by circular dichroism, which suggested that the phase transition of the G/C complex corresponded to the secondary structure (helix‐coil) transition of gelatin. Notably, the UCST of the G/C complex shifted to lower temperatures in the presence of urea, which is well known to destabilize gelatin, whereas the addition of salt led to the dissolution of the G/C complex. It is envisaged that the results of this study will have a significant impact on the fabrication of UCST‐type thermosensitive materials, which can be utilized under aqueous physiological conditions using well‐known biopolymers. This protein‐derived functional material, which responds to the secondary structure transition, could also be used for the development of novel UCST‐type thermosensitive biomaterials. Copyright © 2017 John Wiley & Sons, Ltd.     

Converting Poly(Methyl Methacrylate) into a Triple-Responsive Polymer

Multiresponsive polymers that can respond to several external stimuli are promising materials for a manifold of applications. Herein, a facile method for the synthesis of triple-responsive (pH, temperature, CO₂) poly(N,N-diethylaminoethyl methacrylamide) by a post-polymerization amidation of poly(methyl methacrylate) (PMMA) is presented. Combined with trivalent counterions ([Fe(CN)₆]³⁻) both an upper and lower critical solution temperature (UCST/LCST)-type phase behavior can be realized at pH 8 and 9. PMMA and PMMA-based block copolymers are readily accessible by living anionic and controlled radical polymerization techniques, which opens access to various responsive polymer architectures based on the developed functionalization method. This method can also be applied on melt-processed bulk PMMA samples to introduce functional, responsive moieties at the PMMA surface.     

Synthesis and UCST‐type phase behavior of OEGylated poly(γ‐benzyl‐l‐glutamate) in organic media

A series of OEGylated poly(γ‐benzyl‐l ‐glutamate) with different oligo‐ethylene‐glycol side‐chain length, molecular weight (MW = 8.4 × 10³ to 13.5 × 10⁴) and narrow molecular weight distribution (PDI = 1.12–1.19) can be readily prepared from triethylamine initiated ring‐opening polymerization of OEGylated γ‐benzyl‐l ‐glutamic acid based N‐carboxyanhydride. FTIR analysis revealed that the polymers adopted α‐helical conformation in the solid‐state. While they showed poor solubility in water, they exhibited a reversible upper critical solution temperature (UCST)‐type phase behavior in various alcoholic organic solvents (i.e., methanol, ethanol, 1‐propanol, 1‐butanol, 1‐pentanol, and isopropanol). Variable‐temperature UV–vis analysis revealed that the UCST‐type transition temperatures (T_pts) of the resulting polymers were highly dependent on the type of solvent, polymer concentration, side‐ and main‐chain length. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 1348‐1356     

Polymethacrylamide—An underrated and easily accessible upper critical solution temperature polymer: Green synthesis via photoiniferter reversible addition–fragmentation chain transfer polymerization and analysis of solution behavior in water/ethanol mixtures

Within the group of stimuli-responsive, “smart” materials, upper critical solution temperature (UCST) polymers remain sparsely investigated. Thus, this work focusses on a vastly ignored UCST polymer: polymethacrylamide (PMAAm). A cost-efficient photoiniferter reversible addition–fragmentation chain transfer (RAFT) polymerization yielding narrowly dispersed (Đ < 1.1) PMAAm is presented. This PMAAm exhibits highly thermoreversible UCST-type phase transitions (PT) in water/ethanol mixtures (ethanol content: 17–35 wt%) which are investigated via temperature dependent dynamic light scattering (DLS). Apart from the ethanol content, the PT temperature is affected by polymer mass fraction and chain length and varies between 10–80 °C depending on the three mentioned parameters. Lastly, PMAAm's propensity towards amide hydrolysis and concomitant PT-suppression is investigated. Below temperatures of 40 °C, PMAAm solutions show no sign of amide hydrolysis for at least three days, however, if heated to 70 °C, the thermoresponsiveness gradually degrades within hours.     

Synthesis,Characterization, and thermoresponsive properties of Helical Polypeptides Derivatized from Poly(γ−4‐(3‐chloropropoxycarbonyl)benzyl‐L‐glutamate)

A series of side‐chain‐functionalized α‐helical polypeptides, i.e., poly(γ‐4‐(3‐chloropropoxycarbonyl)benzyl‐_L‐glutamate) (6) have been prepared from n‐butylamine initiated ring‐opening polymerization (ROP) of γ‐4‐(3‐chloropropoxycarbonyl)benzyl‐_L‐glutamic acid‐based N‐carboxyanhydride. Polypeptides bearing oligo‐ethylene‐glycol (OEG) groups or 1‐butylimidazolium salts were prepared from 6 via copper‐mediated [2+3] alkyne‐azide 1,3‐dipolar cycloaddition or nuleophilic substitution, respectively. CD and FTIR analysis revealed that the polymers adopt α‐helical conformations both in solution and the solid state. Polymers bearing OEG (m = 3) side‐chains showed reversible LCST‐type phase transition behaviors in water while polymers bearing 1‐butylimidazolium and I^? counter‐anions exhibited reversible UCST‐type transitions in water. Variable‐temperature UV‐vis analysis revealed that the phase transition temperatures (T_pts) were dependent on the main‐chain length and polymeric concentration. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 2469–2480     

Phase behavior in mixtures of a homopolymer and a block copolymer. 4. SALS and SAXS studies

Phase behavior of blends of poly(vinyl methyl ether) (PVME) with four styrene-butadiene-styrene (SBS) triblock copolymers, being of various molecular weights, architecture, and compositions, was investigated by small-angle light scattering. Small-angle X-ray scattering investigation was accomplished for one blend. Low critical solution temperature (LCST) and a unique phase behavior, resembling upper critical solution temperature (UCST), were observed. It was found that the architecture of the copolymer greatly influenced the phase behavior of the blends. Random phase approximation theory was used to calculate the spinodal phase transition curves of the ABA/C and BAB/C systems; LCST and resembling UCST phase behavior were observed as the parameters of the system changed. Qualitatively, the experimental and the theoretical results are consistent with each other. © 1996 John Wiley & Sons, Inc.     

Phase equilibria and phase separation dynamics in a polymer composite containing a main-chain liquid crystalline polymer

Various topological phase diagrams of blends of main-chain liquid crystalline polymer (MCLCP) and flexible polymer have been established theoretically in the framework of Matsuyama–Kato theory by combining Flory–Huggins (FH) free energy for isotropic mixing, Maier–Saupe (MS) free energy for nematic ordering in the constituent MCLCP, and free energy pertaining to polymer chain-rigidity. As a scouting study, various phase diagrams of binary flexible polymer blends have been solved self-consistently that reveal a combined lower critical solution temperature (LCST) and upper critical solution temperature (UCST), including an hourglass phase diagram. The calculated phase diagrams exhibit liquidus and solidus lines along with a nematic–isotropic (NI) transition of the constituent MCLCP. Depending on the strengths of the FH interaction parameters and the anisotropic (nematic–nematic) interaction parameters, the self-consistent solution reveals an hourglass type phase diagram overlapping with the NI transition of the constituent MCLCP. Subsequently, thermodynamic parameters estimated from the phase diagrams hitherto established have been employed in the numerical computation to elucidate phase separation dynamics and morphology evolution accompanying thermal-quench induced phase separation of the MCLCP/polymer mixture. © 2006 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 44: 3621-3630, 2006     

Novel Thermosensitive IPN Hydrogel Having a Phase Transition Without Volume Change

A novel thermosensitive interpenetrating network (IPN) hydrogel was prepared from an aqueous solution of poly[3,3‐dimethyl(methacryloyloxyethyl)propylammonium sulfonate] infiltrating a crosslinked sulfobetaine polymer, poly(2‐acrylamido‐2‐methylpropylsulfonic acid). The IPN gel shows an upper critical solution temperature (UCST) depending on the molar ratio of the components and the presence of salt. In contrast to conventional gels, the IPN gel exhibits no volume phase transition after traversing the UCST.     

Stimuli-Responsive Polymers in Solution Investigated by NMR and Infrared Spectroscopy

Summary: Temperature-induced and solvent composition-induced phase separation in solutions of poly(N-isopropylmethacrylamide) (PIPMAm) and other thermoresponsive polymers as studied by NMR and infrared (IR) spectroscopy is discussed. The fraction p of phase-separated units (units with significantly reduced mobility) and subsequently, e.g., thermodynamic parameters characterizing the coil-globule phase transition induced by temperature, were determined from reduced integrated intensities in high-resolution ¹H NMR spectra. This approach can be especially useful in investigations of phase separation in solutions of binary polymer systems. Information on behaviour of water during temperature-induced phase transition was obtained from measurements of ¹H NMR relaxation times of HDO molecules. NMR and IR spectroscopy were used to investigate PIPMAm solutions in water/ethanol (D₂O/EtOH) mixtures where the phase separation can be induced by solvent composition (cononsolvency). Some differences in globular-like structures induced by temperature and solvent composition were revealed by these methods.     

UCST and LCST phase behavior of poly(trimethylene ether) glycol in water

We describe the initial studies of the complex aqueous phase behavior of poly(trimethylene ether) glycol (PO3G), a renewably sourced polyether glycol. Cloud point measurement revealed that a low molecular weight PO3G exhibits both lower critical solution temperature (LCST) and upper critical solution temperature (UCST) in water in the temperature range between 30°C and 80°C. At low concentrations of PO3G, the polymer solutions exhibit LCST‐type phase behavior. In the intermediate concentration ranges, PO3G and water are immiscible. However, at higher concentrations of PO3G, the solutions show UCST‐type phase behavior. In addition, both the LCSTs and UCSTs can be easily tuned over a wide range by varying the amount of alcohol co‐solvents. These findings have potential applications in the design of personal care applications and in the development of thermosensitive “smart” materials. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012