UCST Transition Research Articles

Fluorescent, pH, and UCST Responsive Polymer Nanomaterials for Treatment of Recurrent Miscarriage.

Recurrent miscarriage (RM), defined as three or more consecutive spontaneous miscarriages, affects many women of childbearing age. The pathological basis of RM is an imbalance in apoptosis, with the MDM2-p53 pathway playing a crucial role. In this study, we synthesized poly(6-acetoxyl-ε-caprolactone)-graft-(4-amino-benzimidazole) (PCCL-4-ABI) by modifying poly(6-acetoxyl-ε-caprolactone) (PCCL) with 4-amino-benzimidazole (4-ABI). The introduction of carboxyl and 4-ABI groups endowed the PCL backbone with fluorescence, pH responsiveness, and UCST responsiveness. The temperature-dependent release behavior of compound 1-loaded PCCL-4-ABI nanofluorescent materials was attributed to UCST transition. We successfully developed a novel nanofluorescent polymer drug delivery platform, PCCL-4-ABI@1, and evaluated its regulatory effects on p53 and MDM2 in trophoblast cells (HTR-8/SVneo). The results showed that the system loaded with low molecular weight heparin increased MDM2 and decreased p53 expression in a dose-dependent manner, thereby inhibiting trophoblast cell apoptosis. This study developed a biodegradable poly(ε-caprolactone) with UCST behavior, significant for the advancement of thermoresponsive fluorescent nanoparticle systems.

Thermoresponsive homo-polymeric ionic liquid as molecular transporters via tailoring interchain π-π interactions and its unique temp-resistance behavior during ions pairing

In this study, a polymeric ionic liquid (PIL) called Poly[ECH-BIM]Cl was polymerized by ring-opening and quaternization reaction of benzimidazole and epichlorohydrin without additional ion-exchange reaction. Both 1H NMR and fourier transform infrared (FTIR) confirmed the chemical structure of Poly[ECH-BIM]Cl. Poly[ECH-BIM]Cl in water was thermoresponsive and its UCST transition was studied by UV–vis spectrometry, dynamic light scattering (DLS) and scanning electron microscopy (SEM) at variable temperature. Moreover, the first introduced Temp-resistance behavior during ions pairing found Poly[ECH-BIM]Cl had properties similar to those of the precipitation of inorganic salts from their saturated solutions. The variable-temperature 1H NMR analysis demonstrated that the tailored interchain π-π interactions promoted the aggregation of macromolecular chains and particles formed from Poly[ECH-BIM]Cl aqueous solution. The results showed that increasing the interaction between cations of PIL can endow its thermosensibility and the possibility of being a programmable shuttle.

Does Chain Confinement Affect Thermoresponsiveness? A Comparative Study of the LCST and Induced UCST Transition of Tailored Grafting-to Polyelectrolyte Brushes

Does Chain Confinement Affect Thermoresponsiveness? A Comparative Study of the LCST and Induced UCST Transition of Tailored Grafting-to Polyelectrolyte Brushes

Temperature-dependent reentrant phase transition of RNA-polycation mixtures.

Liquid-liquid phase separation (LLPS) of multivalent biopolymers is a ubiquitous process in biological systems and is of importance in bio-mimetic soft matter design. The phase behavior of biomolecules, such as proteins and nucleic acids, is typically encoded by the primary chain sequence and regulated by solvent properties. One of the most important physical modulators of LLPS is temperature. Solutions of proteins and/or nucleic acids have been shown to undergo liquid-liquid phase separation either upon cooling (with an upper critical solution temperature, UCST) or upon heating (with a lower critical solution temperature, LCST). However, many theoretical frameworks suggest the possibility of more complex temperature-dependent phase behaviors, such as an hourglass or a closed-loop phase diagram with concurrent UCST and LCST transitions. Here, we report that RNA-polyamine mixtures undergo a reentrant phase separation with temperature. Specifically, at low temperatures, RNA-polyamine mixtures form a homogenous phase. Increasing the temperature leads to the formation of RNA-polyamine condensates. A further increase in temperature leads to the dissolution of condensates, rendering a reentrant homogenous phase. This dual-response phase separation of RNA is not unique to polyamines but also observed with short cationic peptides. The immiscibility gap is controlled by the charge of the polycation, salt concentration, and mixture composition. Based on the existing theories of complex coacervation, our results point to a complex interplay between desolvation entropy, ion-pairing, and electrostatic interactions in dictating the closed-loop phase behavior of RNA-polycation mixtures.

Multiresponsive Transitions of PDMAEMA Brushes for Tunable Surface Patterning.

Poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA) is an attractive polymer for switchable surface coatings based on its multiresponsiveness toward environmental triggers (temperature, pH-value, ionic strength). In this in situ study, we present the complex and tunable thermoresponsiveness of PDMAEMA Guiselin brushes (9 nm, dry thickness), which were prepared via an efficient grafting-to approach. Combining in situ atomic force microscopy (AFM) visualizing the surface topography (x-y plane) and spectroscopic ellipsometry monitoring the swelling behavior of the polymer film (layer thickness, z-direction) offers for the first time a three-dimensional insight into thermoresponsive transitions on the nanoscale. While PDMAEMA films exhibit LCST behavior in the presence of monovalent counterions, it can easily be switched toward an UCST thermoresponsiveness via the addition of small quantities of multivalent ions. In both cases, the transition temperature as well as the sharpness and reversibility of the transition can be tuned via a second external trigger, the ionic strength. Whereas homogeneous surfaces were observed both below and above the LCST in monovalent salt solutions, the UCST transition was characterized by the in situ formation of a nanostructured surface of pinned PDMAEMA micelles with entrapped multivalent counterions. Moreover, it was demonstrated for the first time that the characteristic dimensions of the nanopattern (the diameter and height of the pinned micelles) could be tuned in situ by the pH- and induced UCST thermoresponsiveness of PDMAEMA. This approach therefore provides a novel bottom-up strategy to create and control polymeric nanostructures in an aqueous environment.

Thermo- and redox-responsive dumbbell-shaped copolymers: from structure design to the LCST–UCST transition

Redox- and thermo-responsive dumbbell-shaped copolymers and their self-assembly and stimuli-responsive properties were investigated.

Enzymatically degradable star polypeptides with tunable UCST transitions in solution and within layer-by-layer films

Enzymatically degradable star polypeptides exhibit robust UCST-type transitions in aqueous solution and within layer-by-layer assembled films.

Multi-responsive hydrogels with UCST- and LCST-induced shrinking and controlled release behaviors of rhodamine B

By using a disulfide-functionalized crosslinker, a pH- and thermo-responsive 2-(dimethylamino) ethyl methacrylate (DMAEMA) monomer and a zwitterionic sulfobetaine methacrylate (SBMA) monomer were conjugated to fabricate a multi-responsive P(DMAEMA-SS-SBMA) copolymeric hydrogel. Apparent UCST and LCST volume transitions were observed in the P(DMAEMA-SS-SBMA) hydrogels with equivalent weight fractions of monomers. Different pore size and response sensitivity of shrunken structures below UCST and above LCST were visualized by SEM images. The hydrogel exhibited a highly swollen state with a swelling ratio of 17.8 and a pore size of 106μm at 45°C, they deswelled unequally at 5°C with a compact surface with pore size of 30μm and a loose bulk with pore size of 83μm, while they deswelled uniformly at 65°C with dense shrunken structure with small pore size of 12μm. The dual-thermoresponsive hydrogel was promising in controlled drug release. The initial drug release was predominantly controlled by diffusion, and the long-term release was influenced by the swelling ratio. Below UCST, the relatively hydrophilic shrunken structure and slow diffusion had a synergistic effect on the sustained release. Above LCST, the fast diffusion and the rapid “off” effect of hydrophobic skin layer resulted in a burst release. Additionally, pH-tunable swelling and redox-sensitive degradation were also observed.

CO2-Triggered UCST transition of amphiphilic triblock copolymers and their self-assemblies

Self-assembled vesicles presenting morphological transformations (vesicles–micelles–unimers) upon external stimuli due to their CO2 adjustable UCST behavior in aqueous solution.

Triple Hydrophilic UCST–LCST Block Copolymers

Thermosensitive ABC triblock copolymers with different block lengths and block orders were prepared by reversible addition–fragmentation chain transfer (RAFT) polymerization. Using a nonionic macro-RAFT agent containing poly(ethylene oxide) (PEO, average degree of polymerization 17), either N-acryloylglycinamide (NAGA) or N-isopropylacrylamide (NIPAM) was first polymerized to diblock copolymers. The diblock copolymers exhibited typical thermoresponsive character of PNAGA and PNIPAM in aqueous solutions. Chain extension of the diblock copolymers was then made to prepare PEO-b-PNAGA-b-PNIPAM and PEO-b-PNIPAM-b-PNAGA triblock copolymers. Investigations of the polymer solutions showed that the triblock copolymers exhibited both UCST and LCST type transitions. The phase transitions induced the formation of polymer aggregates below UCST and above LCST, and the aggregate structures were inverted upon heating and cooling. The order of the polymer blocks with respect to PEO as well as the block sizes contributed t...

Sequence heuristics to encode phase behaviour in intrinsically disordered protein polymers.

Proteins and synthetic polymers that undergo aqueous phase transitions mediate self-assembly in nature and in man-made material systems. Yet little is known about how the phase behaviour of a protein is encoded in its amino acid sequence. Here, by synthesizing intrinsically disordered, repeat proteins to test motifs that we hypothesized would encode phase behaviour, we show that the proteins can be designed to exhibit tunable lower or upper critical solution temperature (LCST and UCST, respectively) transitions in physiological solutions. We also show that mutation of key residues at the repeat level abolishes phase behaviour or encodes an orthogonal transition. Furthermore, we provide heuristics to identify, at the proteome level, proteins that might exhibit phase behaviour and to design novel protein polymers consisting of biologically active peptide repeats that exhibit LCST or UCST transitions. These findings set the foundation for the prediction and encoding of phase behaviour at the sequence level.

DNA–Gelatin Complex Coacervation, UCST and First-Order Phase Transition of Coacervate to Anisotropic ion gel in 1-Methyl-3-octylimidazolium Chloride Ionic Liquid Solutions

Study of kinetics of complex coacervation occurring in aqueous 1-octyl-3-methylimidazolium chloride ionic liquid solution of low charge density polypeptide (gelatin A) and 200 base pair DNA, and thermally activated coacervate into anisotropic gel transition, is reported here. Associative interaction between DNA and gelatin A (GA) having charge ratio (DNA:GA = 16:1) and persistence length ratio (5:1) was studied at fixed DNA (0.005% (w/v)) and varying GA concentration (C(GA) = 0-0.25% (w/v)). The interaction profile was found to be strongly hierarchical and revealed three distinct binding regions: (i) Region I showed DNA-condensation (primary binding) for C(GA) < 0.10% (w/v), the DNA ζ potential decrease from -80 to -5 mV (95%) (partial charge neutralization), and a size decrease by ≈60%. (ii) Region II (0.10 < C(GA) < 0.15% (w/v)) indicated secondary binding, a 4-fold turbidity increase, a ζ potential decrease from -5 to 0 mV (complete charge neutralization), which resulted in the appearance of soluble complexes and initiation of coacervation. (iii) Region III (0.15 < C(GA) < 0.25% (w/v)) revealed growth of insoluble complexes followed by precipitation. The hydration of coacervate was found to be protein concentration specific in Raman studies. The binding profile of DNA-GA complex with IL concentration revealed optimum IL concentration (=0.05% (w/v)) was required to maximize the interactions. Small angle neutron scattering (SANS) data of coacervates gave static structure factor profiles, I(q) versus wave vector q, that were remarkably similar and invariant of protein concentration. This data could be split into two distinct regions: (i) for 0.0173 < q < 0.0353 Å(-1), I(q) ~ q(-α) with α = 1.35-1.67, and (ii) for 0.0353 < q < 0.35 Å(-1), I(q) = I(0)/(1 + q(2)ξ(2)). The correlation length found was ξ = 2 ± 0.1 nm independent of protein concentration. The viscoelastic length (≈8 nm) was found to have value close to the persistence length of the protein (≈10 nm). Rheology data indicated that the coacervate phase resided close to the gelation state of the protein. Thus, on a heating-cooling cycle (heating to 50 °C followed by cooling to 20 °C), the heterogeneous coacervate exhibited an irreversible first-order phase transition to an anisotropic ion gel. This established a coacervate-ion gel phase diagram having a well-defined UCST.

Comparison between the LCST and UCST Transitions of Double Thermoresponsive Diblock Copolymers: Insights into the Behavior of POEGMA in Alcohols

Doubly thermoresponsive polymers consisting of a poly[oligo(ethylene glycol) methyl ether methacrylate] (POEGMA) block displaying UCST behavior in alcohols and a block of poly(N-isopropylacrylamide) (PNIPAM) or poly(N,N-diethylacrylamide) (PDEAM), each of which has an LCST in water, were synthesized using RAFT polymerization followed by simultaneous activated ester/amine and nucleophilic thiol–ene postpolymerization conversions. Upon heating aqueous solutions of POEGMA-b-PNIPAM, 1H NMR spectroscopy confirmed a sudden decrease of the PNIPAM signals at the LCST, indicating dehydration and chain collapse. Dynamic light scattering (DLS) and turbidity measurements observed the macroscopic phase separation of the PNIPAM block at the same temperature. In 2-propanol, 1H NMR spectroscopy showed a gradual decrease of the POEGMA signals over a range of more than 30 °C during its UCST transition, indicating early stages of chain crumpling up to 20 °C above the macroscopic phase separation. The OEG side chains were found to collapse onto the backbone starting at the ester linkages, indicating the most unfavorable enthalpic polymer–solvent interactions occur adjacent to the ester group. Although the diblock copolymers displayed a strong concentration-dependent cloud point, 1H NMR spectroscopy revealed a concentration-independent desolvation, indicating the potential for applications that are not based on phase separation but on changes of polymer conformation. The phase separation occurred within a narrow temperature range of ∼6 °C as evidenced by turbidity and DLS. This transition could be exploited to self-assemble POEGMA-b-PDEAM into micellar structures with POEGMA cores in 1-octanol. Cooling to ∼15 °C below the cloud point was necessary to produce compact structures. Upon heating, the aggregates remained compact until redissolving entirely within a range of 1 °C, making the UCST of POEGMA in alcohols a valuable tool for reversible self-assembly applications.

Entanglement and phase separation in hyperbranched polymer/linear polymer/solvent ternary blends

Hyperbranched polyethylene (HBPE)/linear polystyrene (PS)/chloroform (CF) solution was selected as a model system to investigate the effect of branching structure on entanglement and phase separation behavior in semi-dilute ternary polymer solutions. All the HBPE materials in this work were found to have similar chain architectures and the critical molecular weight was estimated to be 81.2 kDa. The results obtained by elastic light scattering and intrinsic fluorescence methods suggested that all ternary solutions exhibited UCST transition behavior upon cooling. Also, it was found that the increase in the molecular weight of PS led to increase in the phase separation rate, consistent with de Gennes prediction. However, the increase of molecular weight of HBPE did not monotonously reduce the compatibility of polymer components and the phase separation rate in ternary blends is as follows: medium molecular weight HBPE (HBPE-M) > high molecular weight HBPE (HBPE-H) > low molecular weight HBPE (HBPE-L). This abnormal behavior can be explained by the fact that, (i) for HBPE-L, no entanglements between HBPE chains occurred and the branching effect can be ignored, and (ii) for HBPE-M and HBPE-H, entanglement of HBPE chains can be formed, and the dilution of branches on entanglement of backbones should be taken into consideration, that is, the shorter the branches of HBPE, the higher the possibility of interpenetration of HBPE backbones between neighboring molecules and, consequently, the faster aggregation of HBPE during phase separation. Furthermore, a simple model based on decomposition reaction was proposed to quantitatively describe the phase separation kinetics and the apparent activation energies of phase separation were calculated to be −150.3 and −52.3 kJ/mol for HBPE-M/PS/CF and HBPE-H/PS/CF systems, respectively.

Temperature Induced Solubility Transitions of Various Poly(2-oxazoline)s in Ethanol-Water Solvent Mixtures

The solution behavior of a series of poly(2-oxazoline)s with different side chains, namely methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, pentyl, hexyl, heptyl, octyl, nonyl, phenyl and benzyl, are reported in ethanol-water solvent mixtures based on turbidimetry investigations. The LCST transitions of poly(2-oxazoline)s with propyl side chains and the UCST transitions of the poly(2-oxazoline)s with more hydrophobic side chains are discussed in relation to the ethanol-water solvent composition and structure. The poly(2-alkyl-2-oxazoline)s with side chains longer than propyl only dissolved during the first heating run, which is discussed and correlated to the melting transition of the polymers.

PMMA based soluble polymeric temperature sensors based on UCST transition and solvatochromic dyes

Poly(methyl methacrylate) copolymers labeled with a UV/vis or fluorescent dye were synthesized by RAFT polymerization and subsequently investigated as optical or fluorescent temperature sensors in ethanol. The UCST transition of PMMA in combination with solvatochromic dyes was found to result in a wide linear temperature response and to provide insights into the structural conformation of the PMMA chains during the UCST phase transition.

Stimuli-Sensitive Behaviour of Binary Graft Co-polymers (PP-g-DMAEMA)-g-NIPAAm and (PP-g-4VP)-g-NIPAAm in Acidic and Basic Medium

The thermo-sensitive behaviour of the graft co-polymers (PP-g-DMAEMA)-g-NIPAAm and (PP-g-4VP)-g-NIPAAm, synthesized using gamma rays, was studied under basic and acidic conditions. Dependence of pH on the LCST value was also studied by measuring the swelling percentage at different temperatures. Both graft co-polymers were shown to have LCST and UCST behaviours. UCST behaviour was found at acidic pH for both co-polymers. Behaviour towards UCST or LCST transition of graft co-polymers was dependent of NIPAAm content in acidic medium below their pK a. Response to pH was also studied at temperature above LCST.

SANS from Poly(ethylene oxide)/Water Systems

The poly(ethylene oxide) (PEO)/water system is investigated using small-angle neutron scattering (SANS). This system associates to form hydrogen-bonded clusters at high enough concentrations. Two correlation lengths are observed: one long range representing cluster sizes and the other short range representing polymer chain correlations. Clusters are formed at a volume fraction of 4% hPEO in D2O. An LCST transition is obtained between a mixed phase (through hydrogen bonding) and a demixed two-phase region. Solvent deuteration is seen to enhance hydrogen bonding. Deuteration of the polymer backbone is seen to enhance hydrophobic interactions. The average polymer contrast match method fails due to the isotopic dependence of specific interactions. Pressure was seen to lower the LCST by breaking hydrogen bonds. At even higher temperature (beyond the boiling point of water) a UCST transition was observed.

Phase behavior of binary ethylene-propylene copolymer solutions in sub- and supercritical ethylene and propylene

Abstract Temperature-pressure and pressure-concentration cloud-point transitions were measured for solutions of ethylene-propylene copolymer (PEP) in ethylene and in propylene in the critical region. The cloud points were visually observed in variable-volume optical cells up to 200°C and 2000 bar. While UCST, LCST, and U-LCST transitions were observed for PEP solutions in propylene, only U-LCST behavior was observed for PEP solutions in ethylene for the molecular weight range investigated (790–96000 g mol ). Statistical Associated Fluid Theory (SAFT) was used to correlate the experimental cloud points.

Density-tuned polyolefin phase equilibria. 2. Multicomponent solutions of alternating poly(ethylene-propylene) in subcritical and supercritical olefins. Experiment and SAFT model

A combination of a high pressure exoeriment (variable-volume optical cell) and molecular theory (statistical associating fluid theory SAFT) is used to quantify systematically the effe ts of pressure, temperature, composition and polymer and solvent size on LCST, UCST, VL and VLL transitions in binary, ternary and quaternary olefin-polyolefin systems. Supercritical ethylene is found to reduce drastically the mutual miscibility of 1-butene+poly(ethylene-alt-propylene) (PEP) and 1-hexene+PEP and hence, to increase the LCST pressures needed to maintain the ternary mixtures in a one-phase region. This ethylene antisolvent effect is modeled with SAFT