Coil-globule Transition Research Articles

Protic Ionic Liquids for the Belousov-Zhabotinsky Reaction: Aspects of the BZ Reaction in Protic Ionic Liquids and Its Use for the Autonomous Coil-Globule Oscillation of a Linear Polymer.

Herein, we describe the physicochemical aspects of the Belousov-Zhabotinsky (BZ) reaction in hydrated protic ionic liquids (PILs) combined with different cations with a hydrogen sulfate ([HSO4-]) anion. PILs were prepared from the neutralization reactions of sulfuric acid with 13 different aliphatic amines. The amine structure was selected to investigate the effect of the number of active protons, alkyl chain length (hydrophilicity), and cationic linearity on the mechanism of the BZ reaction. The pKa values of PILs were significantly higher (pKa = 1.0-2.5) than those of inorganic acids (H2SO4 = -3.0; HNO3 = -1.4), the conventional proton source in a BZ reaction. A periodic redox oscillation was observed in Ru(bpy)3 when appropriate amounts of BZ reaction substrates (NaBrO3 oxidant; malonic acid reductant) were added to the hydrated PILs. A long-lasting BZ oscillation was realized when hydrophilic cations (ammonium, ethylammonium, and dimethylethylammonium) were employed. Interestingly, a large ΔA5000 (oscillation amplitude of absorbance for the scale of the oscillation stability observed after 5000 s from the initiation of the BZ reaction) was achieved for PILs possessing less than four carbon atoms in their cationic structure. The apparent BZ oscillation activation energy (Ea) in the hydrated PILs was estimated to be ∼40 kJ mol-1, which is 30 kJ mol-1 less than that observed in a conventional system. The catalytic reaction in the BZ reaction subprocess suppresses the total activation energy of the reaction. To realize long-lasting self-oscillating polymeric materials acting under milder condition, we demonstrated an autonomous coil-globule polymer chain transition (BZ-driven) that directly converts chemical energy to mechanical motion in hydrated PILs without freely diffusing Ru(bpy)3 metal catalyst. Ethylammonium hydrogen sulfate ([ea-H+][HSO4-]) is selected as the suitable proton source for the BZ reaction. A well-defined self-oscillating polymer that incorporated Ru(bpy)3 metal catalyst into the polymer backbone accompanied by good compatibility in hydrated [ea-H+][HSO4-] is successfully prepared by ATRP, followed by postmodification of the metal catalyst. The rhythmic solubility changes of the polymer under milder conditions, realized by combination with PILs, will expand the potential applications of PILs to novel functional materials.

Polymer chain collapse induced by many-body dipole correlations.

We present a simple analytical theory of a flexible polymer chain dissolved in a good solvent, carrying permanent freely oriented dipoles on the monomers. We take into account the dipole correlations within the random phase approximation (RPA), as well as a dielectric heterogeneity in the internal polymer volume relative to the bulk solution. We demonstrate that the dipole correlations of monomers can be taken into account as pairwise ones only when the polymer chain is in a coil conformation. In this case the dipole correlations manifest themselves through the Keesom interactions of the permanent dipoles. On the other hand, the dielectric heterogeneity effect (dielectric mismatch effect) leads to the effective interaction between the monomers of the polymeric coil. Both of these effects can be taken into account by renormalizing the second virial coefficient of the monomer-monomer volume interactions. We establish that in the case when the solvent dielectric permittivity exceeds the dielectric permittivity of the polymeric material, the dielectric mismatch effect competes with the dipole attractive interactions, leading to polymer coil expansion. In the opposite case, both the dielectric mismatch effect and the dipole attractive interaction lead to the polymer coil collapse. We analyse the coil-globule transition caused by the dipole correlations of monomers within the many-body theory. We demonstrate that accounting for the dipole correlations higher than the pairwise ones smooths this pure electrostatics driven coil-globule transition of the polymer chain.

Formation of DNA pearl‐necklace structures on mica surface governed by kinetics and thermodynamics

ABSTRACTPolyelectrolytes (PEs) possibly occur in the form of a pearl‐necklace structure in poor solvents. This structure, characterized by the form of segregated beads connected by narrow strings, has been extensively studied by scaling analysis and computer simulation, and was believed to be formed by the Rayleigh instability mechanism. However, the structure has not been experimentally well studied, and a complete experimental picture on the necklace formation is still not available. In this study, pearl‐necklace structures of DNA induced by different condensing agents are observed by atomic force microscopy. The results show that the formation of a pearl‐necklace conformation is highly dependent on kinetic factors such as incubation time and thermodynamic factors including the concentration and condensing ability of the agent. If the incubation time is sufficiently short, this conformation can exist as an intermediate state of the DNA coil–globule transition. When agents with weaker crowding effect or screening ability are added, the structure appeared to be thermodynamically stable. The same effect was observed in rather low concentrations of agent. A rods‐on‐a‐string structure, unlike the common characterized spherical beads‐on‐a‐string conformation, was observed and was believed to result from the stiffness of DNA. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2017, 55, 971–979

Hydration-Shell Transformation of Thermosensitive Aqueous Polymers.

Although water plays a key role in the coil-globule transition of polymers and biomolecules, it is not clear whether a change in water structure drives or follows polymer collapse. Here, we address this question by using Raman multivariate curve resolution (Raman-MCR) spectroscopy to investigate the hydration shell structure around poly(N-isopropylacrylamide) (PNIPAM) and poly(propylene oxide) (PPO), both below and above the cloud point temperature at which the polymers collapse and form mesoscopic polymer-rich aggregates. We find that, upon clouding, the water surrounding long PNIPAM chains transforms to a less ordered and more weakly hydrogen bonded structure, while the water surrounding short PNIPAM and PPO chains remains similar above and below the cloud point. Furthermore, microfluidic temperature jump studies demonstrate that the onset of clouding precedes the hydration-shell structural transformation, and thus the observed water structural transformation is associated with ripening of aggregates composed of long-chain polymers, on a time scale that is long compared to the onset of clouding.

Crowding Induced Coil-Globule Transitions of Intrinsically Disordered Proteins

Crowding Induced Coil-Globule Transitions of Intrinsically Disordered Proteins

Statistical description of co-nonsolvency suppression at high pressures.

We present an application of Flory-type theory of a flexible polymer chain dissolved in a binary mixture of solvents to theoretical description of co-nonsolvency. We show that our theoretical predictions are in good quantitative agreement with the recently published MD simulation results for the conformational behavior of a Lennard-Jones flexible chain in a binary mixture of the Lennard-Jones fluids. We show that our theory is able to describe co-nonsolvency suppression through pressure enhancement to extremely high values recently discovered in experiments and reproduced by full atomistic MD simulations. By analysing the co-solvent concentration in the internal polymer volume at different pressure values, we speculate that this phenomenon is caused by the suppression of the co-solvent preferential solvation of the polymer backbone at the rather high pressure imposed. We show that when the co-solvent-induced coil-globule transition takes place, the entropy and enthalpy contributions to the solvation free energy abruptly decrease, while the solvation free energy remains continuous.

Single-Molecule FRET Measurements in Additive-Enriched Aqueous Solutions.

The addition of high amounts of chemical denaturants, salts, viscosity enhancers or macro-molecular crowding agents has an impact on the physical properties of buffer solutions. Among others, the (microscopic) viscosity, the refractive index, the dielectric constant, and the ionic strength can be affected. Here, we systematically evaluate the importance of solvent characteristics with respect to single-molecule FRET (smFRET) data. First, we present a confocal based method for the determination of fluorescence quantum yields to facilitate a fast characterization of smFRET-samples at sub-nM-concentrations. As a case study, we analyze smFRET data of structurally rigid, double-stranded DNA-oligonucleotides in aqueous buffer and in buffers with specific amounts of glycerol, guanidine hydrochloride (GdnHCl), and sodium chloride (NaCl) added. We show that the calculation of interdye distances, without taking into account solvent-induced spectral and photophysical changes of the labels, leads to deviations of up to 4 Å from the real interdye distances. Additionally, we demonstrate that electrostatic dye-dye repulsions are negligible for the interdye distance regime considered here (>50 Å). Finally, we use our approach to validate the further compaction of the already unfolded state of phosphoglycerate kinase (PGK) with decreasing denaturant concentrations, a mechanism known as coil-globule transition.

Polarizable polymer chain under external electric field: Effects of many-body electrostatic dipole correlations.

We present a new simple self-consistent field theory of a polarizable flexible polymer chain under an external constant electric field with account for the many-body electrostatic dipole correlations. We show the effects of electrostatic dipole correlations on the electric-field-induced globule-coil transition. We demonstrate that only when the polymer chain is in the coil conformation, the electrostatic dipole correlations of monomers can be considered as pairwise. However, when the polymer chain is in a collapsed state, the dipole correlations have to be considered at the many-body level.

Artificial Control of Gene Silencing Activity Based on siRNA Conjugation with Polymeric Molecule Having Coil-Globule Transition Behavior.

A new strategy for controlling gene silencing activity of siRNA in the cell was developed in the present study. siRNA was linearly conjugated with PNIPAAm, where coil-globule transition of the conjugated PNIPAAm allows thermoresponsive exposure of the vicinal siRNA molecule; a coil form of PNIPAAm (T < LCST) inhibits siRNA interaction with gene silencing-related proteins due to the steric hindrance effect, while a globule form of PNIPAAm (T > LCST) allows a ready access of siRNA to gene silencing pathway. As a result, at T > LCST, PNIPAAm-siRNA elicited effective association of siRNA with a gene silencing-related protein of Ago2, while siRNA recruitment into the gene silencing pathway was significantly suppressed at T < LCST. Ultimately, gene silencing efficacy of PNIPAAm-siRNA was close to unconjugated siRNA at T > LCST (∼80%), while it was dramatically decreased to ∼20% at T < LCST, suggesting that coil-globule transition of the conjugated polymer can control the bioactivity of the vicinal siRNA molecule.

Simulation study on the coil-globule transition of adsorbed polymers

Simulation study on the coil-globule transition of adsorbed polymers

Nanocomposite DNA hydrogels with temperature sensitivity

DNA hydrogels are promising soft materials because of the distinctive properties of DNA such as biocompatibility, coil-globule transition, molecular recognition, and selective binding. However, such hydrogels synthesized so far suffer from poor mechanical properties and low dimensional stability, which limit their stress-bearing technological applications. Here, we introduce a novel concept for the preparation of high-strength double-stranded (ds) DNA hydrogels with temperature sensitivity. The hydrogels were synthesized by free-radical polymerization of N-isopropylacrylamide in aqueous Laponite dispersions containing ds-DNA in a highly entangled state. The nanoparticles of synthetic Laponite clay act as a dynamic cross-linker to form a three-dimensional physical network due to strong clay-polymer interactions. We observed that ds-DNA maintains its native structure and function during the formation of nanocomposite hydrogels. Cyclic heating/cooling experiments conducted between below and above the melting temperature of ds-DNA reveal a drastic increase in the elastic modulus of nanocomposite hydrogels due to the thermally induced denaturation and renaturation of DNA within the physical network. The hydrogels prepared at various Laponite contents display the characteristics of both poly(N-isopropylacrylamide) and ds-DNA e.g., temperature sensitivity, denaturation and renaturation of DNA strands, and they exhibit a high tensile fracture stress (up to 53 kPa) and elongation to break (up to 544%).

Temperature-Induced Coil-Globule Transition of Alkali Metal Polyacrylates in Aqueous Organic Solvent Mixtures

ABSTRACTA counterion-specific coil-globule transition (CGT) has been observed for alkali metal poly(acrylate)s (PAAM, M; Li, Na, K, Cs) in aqueous organic solvent (ethanol, dimethyl sulfoxide, acetone, acetonitrile) mixtures. In the present study we found that the reduced viscosity of PAAM, except for PAALi, in the relevant mixed solvents, except for those containing acetonitrile, significantly increased with increasing temperature. The observed temperature-induced CGT was interpreted as being caused by disintegration of the ion-clusters, i.e., the associated state of contact ion-pairs formed between the polymer charge and the counterion. In fact, the NMR line width of 23Na and 133Cs, which were used as a measure of the counterion mobility, indicated that the counterion binding was significantly weakened with increasing temperature, while the temperature effects for the PAALi and acetonitrile systems were only marginal. All these results suggested that the temperature-induced CGT behavior occurs only for systems where the ion-cluster formation promotes the CGT in the relevant solvent systems, which is also consistent with the known similar behavior of some betaine polymers.

Influence of the polymer structure over self‐assembly and thermo‐responsive properties: The case of PEG‐b‐PCL grafted copolymers via a combination of RAFT and ROP

ABSTRACTDuring the last years, the field of drug delivery has experienced a growing interest toward the so‐called thermo‐responsive polymers: synthetic materials that, due to the specific hydrophilic–lipophilic balance of their repeating units, exhibit a lower critical solution temperature (LCST) in water associated to a characteristic coil–globule transition. In this work, thermo‐responsive amphiphilic block copolymers are synthesized via reversible addition‐fragmentation transfer (RAFT) polymerization starting from thermo‐responsive monomers and a hydrophobic biodegradable macromonomer, oligo(caprolactone)methacrylate (CL3MA), produced via ring opening polymerization (ROP). The obtained copolymers exhibit an interesting self‐assembly behavior leading to nanoparticles (NPs) as long as temperature is kept below the LCST. Otherwise, once this value is overcome, the destabilization of the NPs causes the formation of hydrophobic superstructures that enhance the release of an entrapped lipophilic drug. This characteristic behavior has been systematically studied and related to the copolymer structure. In particular, the self‐assembly behavior as well as temperature‐triggered NP destabilization have been related to the relative length of the two blocks constituting the copolymers and to their hydrophilic–lipophilic balance (HLB). Finally, the efficacy of the thermo‐responsive triggered drug release has been tested in the case of Paclitaxel (PTX). © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016, 54, 2919–2931

A statistical theory of coil-to-globule-to-coil transition of a polymer chain in a mixture of good solvents

We present an off-lattice statistical model of a single polymer chain in mixed-solvent media. Taking into account the polymer conformational entropy, renormalization of solvent composition near the polymer backbone, the universal intermolecular excluded-volume and van der Waals interactions within the self-consistent field theory, the reentrant coil-to-globule-to-coil transition (co-nonsolvency) has been described in this paper. For convenience we split the system volume in two parts: the volume occupied by the polymer chain and the volume of bulk solution. Considering the equilibrium between two sub-volumes, the polymer solvation free energy as a function of radius of gyration and co-solvent mole fraction within internal polymer volume has been obtained. Minimizing the free energy of solvation with respect to its arguments, we show two qulitatively different regimes of co-nonsolvency. Namely, at sufficiently high temperature the reentrant coil-to-globule-to-coil transition proceeds smoothly. On the contrary, when the temperature drops below a certain threshold value a coil-globule transition occurs in the regime of first-order phase transition, i.e., discontinuous changes of the radius of gyration and the local co-solvent mole fraction near the polymer backbone. We show that, when the collapse of the polymer chain takes place, the entropy and enthalpy contributions to the solvation free energy of the globule strongly grow. From the first principles of statistical thermodynamics we confirm earlier speculations based on the MD simulations results that the co-nonsolvency is the essentially enthalpic-entropic effect and is caused by enthalpy-entropy compensation. We show that the temperature dependences of the solution heat capacity change due to the solvation of the polymer chain are in qualitative agreement with the differential scanning calorimetry data for PNIPAM in aqueous methanol.

Mesoscopic simulation of a micellar poly(N-isopropyl acrylamide)-b-(polyethylene oxide) copolymer system

In this article we studied the micellar formation of poly(N-isopropyl acrylamide)-b-polyethylene oxide (PNIPAM-b-PEO) copolymers in an aqueous system. From molecular simulations the dependence on temperature of the Flory–Huggins interaction parameter χ for PNIPAM and PEO in water is obtained and compared with available experimental results and values from other theoretical calculations. By means of dissipative particle dynamics (DPD) we then simulated the coil–globule transition for PNIPAM chains in water with a transition temperature of around 305 K. The simulations for PNIPAM-b-PEO copolymers showed that at room temperature the chains are miscible in an aqueous phase but with a temperature increase the system turns into micelles at T = 305 K. The change in micelle anisotropy due to a different ratio PNIPAM/PEO of chains is also analyzed. What is observed is that for large PEO the large number of dissolved PEO chains gives a large corona size and the micelle is not spherical but obloide and as the number of PNIPAM is increased the micelle acquires a spherical shape. As an important application we considered the system micelle-water/anionic liquid (1-butyl-3-methylimidazolium hexafluorophosphate [BMIM]+[PF6]−). By increasing the temperature of the system from 306 K it is shown that at T = 345 K there is a transfer of the micelle from water to the ionic liquid phase and this was due to the change in the relative affinity of PEO to water and ionic liquid expressed by the change in χ. All the simulation outcomes are qualitatively consistent with experimental results and thus to our knowledge we give the first set of χ values for the interaction between PNIPAM and water in a wide range of temperature values.

Polymers with nearest- and next nearest-neighbor interactions on the Husimi lattice

The exact grand-canonical solution of a generalized interacting self-avoid walk (ISAW) model, placed on a Husimi lattice built with squares, is presented. In this model, beyond the traditional interaction between (nonconsecutive) monomers on nearest-neighbor (NN) sites, an additional energy is associated to next-NN (NNN) monomers. Three definitions of NNN sites/interactions are considered, where each monomer can have, effectively, at most two, four, or six NNN monomers on the Husimi lattice. The phase diagrams found in all cases have (qualitatively) the same thermodynamic properties: a non-polymerized (NP) and a polymerized (P) phase separated by a critical and a coexistence surface that meet at a tricritical (θ-) line. This θ-line is found even when one of the interactions is repulsive, existing for in the range , i.e., for in the range . Thus, counterintuitively, a θ-point exists even for an infinite repulsion between NN monomers (), being associated to a coil–‘soft globule’ transition. In the limit of an infinite repulsive force between NNN monomers, however, the coil–globule transition disappears, and only NP–P continuous transition is observed. This particular case, with , is also solved exactly on the square lattice, using a transfer matrix calculation where a discontinuous NP–P transition is found. For attractive and repulsive forces between NN and NNN monomers, respectively, the model becomes quite similar to the semiflexible-ISAW one, whose crystalline phase is not observed here, as a consequence of the frustration due to competing NN and NNN forces. The mapping of the phase diagrams in canonical ones is discussed and compared with recent results from Monte Carlo simulations on the square lattice.

Structural Fluctuations of the Chromatin Fiber within Topologically Associating Domains

Experiments based on chromosome conformation capture have shown that mammalian genomes are partitioned into topologically associating domains (TADs), within which the chromatin fiber preferentially interacts. TADs may provide three-dimensional scaffolds allowing genes to contact their appropriate distal regulatory DNA sequences (e.g., enhancers) and thus to be properly regulated. Understanding the cell-to-cell and temporal variability of the chromatin fiber within TADs, and what determines them, is thus of great importance to better understand transcriptional regulation. We recently described an equilibrium polymer model that can accurately predict cell-to-cell variation of chromosome conformation within single TADs, from chromosome conformation capture-based data. Here we further analyze the conformational and energetic properties of our model. We show that the chromatin fiber within TADs can easily fluctuate between several conformational states, which are hierarchically organized and are not separated by important free energy barriers, and that this is facilitated by the fact that the chromatin fiber within TADs is close to the onset of the coil-globule transition. We further show that in this dynamic state the properties of the chromatin fiber, and its contact probabilities in particular, are determined in a nontrivial manner not only by site-specific interactions between strongly interacting loci along the fiber, but also by nonlocal correlations between pairs of contacts. Finally, we use live-cell experiments to measure the dynamics of the chromatin fiber in mouse embryonic stem cells, in combination with dynamical simulations, and predict that conformational changes within one TAD are likely to occur on timescales that are much shorter than the duration of one cell cycle. This suggests that genes and their regulatory elements may come together and disassociate several times during a cell cycle. These results have important implications for transcriptional regulation as they support the concept of highly dynamic interactions driven by a complex interplay between site-specific interactions and the intrinsic biophysical properties of the chromatin fiber.

Effects of Complementary DNA and Salt on the Thermoresponsiveness of Poly(N-isopropylacrylamide)-b-DNA.

The thermoresponsive structural transition of poly(N-isopropylacrylamide) (PNIPAAm)-b-DNA copolymers was explored. Molecular assembly of the block copolymers was facilitated by adding salt, and this assembly was not nucleated by the association between DNA strands but by the coil-globule transition of PNIPAAm blocks. Below the lower critical solution temperature (LCST) of PNIPAAm, the copolymer solution remained transparent even at high salt concentrations, regardless of whether DNA was hybridized with its complementary partner to form a double-strand (or single-strand) structure. At the LCST, the hybridized copolymer assembled in spherical nanoparticles, surrounded by double-stranded DNA; subsequently, the non-cross-linking aggregation occurred, while the nanoparticles were dispersed if the salt concentration was low or DNA blocks were unhybridized. When the DNA duplex was denatured to a single-stranded state by heating, the aggregated nanoparticles redispersed owing to the recovery of the steric repulsion of the DNA strands. The changes in the steric and electrostatic effects by hybridization and the addition of salt did not result in any specific attraction between DNA strands but merely decreased the repulsive interactions. The van der Waals attraction between the nanoparticles overcame such repulsive interactions so that the non-cross-linking aggregation of the micellar particles was mediated.

Dimensions, energetics, and denaturant effects of the protein unstructured state.

Determining the energetics of the unfolded state of a protein is essential for understanding the folding mechanics of ordered proteins and the structure-function relation of intrinsically disordered proteins. Here, we adopt a coil-globule transition theory to develop a general scheme to extract interaction and free energy information from single-molecule fluorescence resonance energy transfer spectroscopy. By combining protein stability data, we have determined the free energy difference between the native state and the maximally collapsed denatured state in a number of systems, providing insight on the specific/nonspecific interactions in protein folding. Both the transfer and binding models of the denaturant effects are demonstrated to account for the revealed linear dependence of inter-residue interactions on the denaturant concentration, and are thus compatible under the coil-globule transition theory to further determine the dimension and free energy of the conformational ensemble of the unfolded state. The scaling behaviors and the effective θ-state are also discussed.

A temperature-dependent coarse-grained model for the thermoresponsive polymer poly(N-isopropylacrylamide).

A coarse-grained (CG) model is developed for the thermoresponsive polymer poly(N-isopropylacrylamide) (PNIPAM), using a hybrid top-down and bottom-up approach. Nonbonded parameters are fit to experimental thermodynamic data following the procedures of the SDK (Shinoda, DeVane, and Klein) CG force field, with minor adjustments to provide better agreement with radial distribution functions from atomistic simulations. Bonded parameters are fit to probability distributions from atomistic simulations using multi-centered Gaussian-based potentials. The temperature-dependent potentials derived for the PNIPAM CG model in this work properly capture the coil-globule transition of PNIPAM single chains and yield a chain-length dependence consistent with atomistic simulations.