Phase Behavior Of Aqueous Solutions Research Articles

Experimental and Theoretical Studies on the Phase Behavior of Aqueous Solutions of Structurally Controlled Hyperbranched Poly(N-isopropylacrylamide)s

Structurally controlled hyperbranched poly(N-isopropylacrylamide)s (HB-PNIPAMs) having different branching densities were systematically synthesized, and their phase behavior, i.e., lower critical solution temperatures (LCSTs), in water was studied. The branching significantly affects LCSTs, and they decrease with an increase in the branching density. The origin of the experimental results was theoretically analyzed on the basis of the concept of cooperative hydration, which is the sequential formation of hydrogen bonds between polymer chains and water molecules. Assuming that the cooperativity of hydration does not propagate beyond the branching points, we calculate the spinodal curves, binodal curves, and critical points and construct the phase diagrams. The degrees of hydration of the subchains, branching points, and end groups are also calculated to examine their hydration effect on the phase behavior. In this investigation, we consider the following two situations: (i) only subchains can be hydrated, and (ii) every part of HB polymers, including branching points and end groups, can be hydrated. We compare the theory with the reported observations of the cloud points of structurally well-controlled HB-PNIPAMs in water. Qualitative agreement is obtained by using the same value of cooperativity as the study of aqueous solutions of linear PNIPAMs. We also show that the hydration behavior of the end groups and the branching points strongly influences the phase behavior and illustrate that the binodal temperature is determined by the balance between the effect of promoting hydration by their hydration and suppressing hydration due to the inhibition of cooperative hydration by the branching points.

The phase behaviour of cetyltrimethylammonium chloride surfactant aqueous solutions at high concentrations: an all-atom molecular dynamics simulation study.

We explore the phase behaviour of aqueous solutions of the cetyltrimethyl ammonium chloride (CTAC) surfactant and in particular the transition from the micellar phase (L1) to the hexagonal columnar phase (H1) by employing all-atom (AA) molecular dynamics (MD) simulations for six CTAC concentrations in the range of 34.1 wt% to 70.5 wt%, at the temperature of 318 K and pressure of 1 atm. For the concentrations considered, we examine the spontaneous occurrence of the H1 phase by testing a number of plausible values for the linear density (molecules per unit length) along the cylindrical columns. Using large simulation cells and starting from random initial configurations, the MD simulations demonstrate that the micellar phase occurs for concentrations up to 50.0 wt%, with CTAC molecules self-assembling into a mixture of spherical and rod-like micelles. At even higher concentrations, the system self-organizes into the H1 phase in accordance with the available experimental data. For the analysis of the MD trajectories, we devise a clustering algorithm based on Voronoi tesselation which enables (a) the thorough characterization of the shape and structure of both molecules and assemblies, and (b) the investigation of the positional and orientational order in the system that are further scrutinised using radial pair correlation functions and X-ray diffraction patterns. Our work paves the way for the investigation of the phase behaviour at high concentrations of other surfactants.

Role of entropy in determining the phase behavior of protein solutions induced by multivalent ions.

Recent experiments have reported lower critical solution temperature (LCST) phase behavior of aqueous solutions of proteins induced by multivalent ions, where the solution phase separates upon heating. This phenomenon is linked to complex hydration effects that result in a net entropy gain upon phase separation. To decipher the underlying molecular mechanism, we use all-atom molecular dynamics simulations along with the two-phase thermodynamic method for entropy calculation. Based on simulations of a single BSA protein in various salt solutions (NaCl, CaCl2, MgCl2, and YCl3) at temperatures (T) ranging 283-323 K, we find that the cation-protein binding affinity increases with T, reflecting its thermodynamic driving force to be entropic in origin. We show that in the cation binding process, many tightly bound water molecules from the solvation shells of a cation and the protein are released to the bulk, resulting in entropy gain. To rationalize the LCST behavior, we calculate the ζ-potential that shows charge inversion of the protein for solutions containing multivalent ions. The ζ-potential increases with T. Performing simulations of two BSA proteins, we demonstrate that the protein-protein binding is mediated by multiple cation bridges and involves similar dehydration effects that cause a large entropy gain which more than compensates for rotational and translational entropy losses of the proteins. Thus, the LCST behavior is entropy-driven, but the associated solvation effects are markedly different from hydrophobic hydration. Our findings have direct implications for tuning the phase behavior of biological and soft-matter systems, e.g., protein condensation and crystallization.

Thermoresponsive Glycopolymers Based on Enzymatically Synthesized Oligo-β-Mannosyl Ethyl Methacrylates and N-Isopropylacrylamide.

We present here a series of thermoresponsive glycopolymers in the form of poly(N-isopropylacrylamide)-co-(2-[β-manno[oligo]syloxy] ethyl methacrylate)s. These copolymers were prepared from oligo-β-mannosyl ethyl methacrylates that were synthesized through enzymatic catalysis, and were subsequently investigated with respect to their aggregation and phase behavior in aqueous solution using a combination of 1H NMR spectroscopy, dynamic light scattering, cryogenic transmission electron microscopy (TEM), and small-angle X-ray scattering (SAXS). The thermoresponsive glycopolymers were prepared by conventional free radical copolymerization of different mixtures of 2-(β-manno[oligo]syloxy)ethyl methacrylates (with either one or two saccharide units) and N-isopropylacrylamide (NIPAm). The results showed that below the lower critical solution temperature (LCST) of poly(NIPAm), the glycopolymers readily aggregate into nanoscale structures, partly due to the presence of the saccharide moieties. Above the LCST of poly(NIPAm), the glycopolymers rearrange into a heterogeneous mixture of fractal and disc/globular aggregates. Cryo-TEM and SAXS data demonstrated that the presence of the pendant β-mannosyl moieties in the glycopolymers induces a gradual conformational change over a wide temperature range. Even though the onset of this transition is not different from the LCST of poly(NIPAm), the gradual conformational change offers a variation of the temperature-dependent properties in comparison to poly(NIPAm), which displays a sharp coil-to-globule transition. Importantly, the compacted form of the glycopolymers shows a larger colloidal stability compared to the unmodified poly(NIPAm). In addition, the thermoresponsiveness can be conveniently tuned by varying the sugar unit-length and the oligo-β-mannosyl ethyl methacrylate content.

Extension and Limits of Cryoscopy for Nanoconfined Solutions.

This work investigates the phase behavior of aqueous solutions of glycerol confined in MCM-41 and SBA-15 nanoporous matrixes by calorimetry. Limitations due to overfilling and eutectic freezing are prevented by the absence of an external liquid reservoir and by the glass-forming property of glycerol. Consequently, the stability of nanoconfined ice in equilibrium with aqueous solutions is studied over a wide range of compositions. In confinement, a large temperature depression of the liquidus line is observed. A thermodynamic model accounting simultaneously for the cryoscopic and the Gibbs-Thomson effects gives a consistent view of the phase diagram for large pores (Rp = 4.15 nm). For smaller pores (Rp = 1.8 nm), it reveals that the water activity strongly deviates from the bulk solution with the same composition, indicating the possible role of concentration heterogeneities in determining the onset of ice freezing in strongly nanoconfined solutions.

COSMO-RS predicted 1-octanol/water partition coefficient as useful ion descriptor for predicting phase behavior of aqueous solutions of ionic liquids

Abstract 1-Octanol/water partition coefficients (log P) of 450 cations and 132 anions composing ionic liquids (ILs) were estimated with the conductor-like screening model for real solvents (COSMO-RS). For each cation-anion combination mixed with water, the liquid-liquid equilibrium (LLE) compositions at T = 308.15 K and T = 373.15 K were calculated using COSMO-RS. An influence of cation and anion hydrophobicity (measured by log P) on the phase behavior of the {IL + water} mixture. Distinct domains of log P values corresponding to miscible, immiscible and partial solubility behavior, were observed, in particular those with upper and lower critical solution temperature (UCST/LCST). 18 ILs were chosen from different regions of the resulting plot. The ILs were synthesized and their LLE with water has been measured. The predicted phase behavior is in good agreement with the observed data as well as with the literature data in general. The proposed method is simple and allows for rapid and straightforward evaluation of the phase behavior of {IL + water} systems.

Contrast variation of micelles composed of Ca2+ and block copolymers of two negatively charged polyelectrolytes

Block copolymers were prepared with two anionic polyelectrolyte blocks: sodium polyacrylate (PA) and sodium polystyrene sulfonate (PSS), in order to investigate their phase behavior in aqueous solution in the presence of Ca2+ cations. Depending on the concentration of polymer and Ca2+ and on the ratio of the block lengths in the copolymer, spherical micelles were observed. Micelle formation arises from the specific interaction of Ca2+ with the PA block only. An extensive small-angle scattering study was performed in order to unravel the structure and dimensions of the block copolymer micelles. Deuteration of the PA block enabled us to perform contrast variation experiments using small-angle neutron scattering at variable ratios of light and heavy water which were combined with information from small-angle X-ray scattering and dynamic light scattering.Graphical Block copolymers with two anionic polyelectrolyte blocks, sodium polyacrylate (PA) and sodium polystyrene sulfonate (PSS) self-assemble in response to an addition of Ca2+ cations. Deuteration of the PA block made possible contrast variation experiments using SANS at variable ratios of H2O/D2O, which in combination with SAXS revealed the morphology of the self-assemblies.

Phase behavior of aqueous solutions of ethaline deep eutectic solvent

We have established a detailed phase diagram of a prototypical DES as a function of the hydration level. Two distinct thermal phase behaviors are observed depending on the water content with respect to a cross-over composition Wg’ = 30%. For W < Wg’, the formation of ice is not observed under the experimental conditions used in this study, and the solution falls in the category of glassforming systems. Fully vitreous states could also be obtained between 30% and 50%, but they are metastable with respect to water crystallization. For W > Wg’, ice crystallization occurs but the residual DES solution remains amorphous (liquid or glassy). In the latter case, whatever the initial water fraction, this transformation finally ends at the fixed composition Wg’ corresponding to 6 to 10 water molecules per choline ion for the two studied DESs. We infer that the residual liquid water molecules forming this maximally freeze-concentrated solution are strongly interacting with DES molecular units. This situation is also known as the “water-in-DES” case. Conversely, ice crystallization concerns free water molecules, provided that W > Wg’, also known as the “DES-in-water” case. This entire phase behavior is explained in the context of maximally freeze-concentrated solutions and attributed to the concomitant effects of ice freezing depression, glassforming ability of weakly hydrated DES (W < Wg’) and water structure distortion. This study also highlights the potential of DESs for their uses in freeze-drying processes and biopreservative applications.

Hand-holding and releasing between the anion and cation to change their macroscopic behavior in water

Despite the similarity of ionic liquid and zwitterion, their some properties such as conductivity and hydrophobicity are different. Here we developed a novel phosphonium salt having a dynamic covalent bond between anion and cation, enabling reversible structural shift between free ion pair and zwitterion. With the phosphonium salt, control of the macroscopic phase behavior in aqueous solution, i.e. forming mono- or bi-phasic systems, upon exposure to an acid or base was reversibly achieved, based on the structural shift of the phosphonium salt. CO2/N2 bubbling reversibly changed the phase behavior as well as acid/base, leading to green separation systems.

The significant effects of linear medium chain fatty alcohols on phase behavior of aqueous solution of mixed cationic–anionic surfactant

The effect of 1-hexanol on the phase behavior of aqueous solutions of sodium dodecyl sulfate (SDS) and cetyl trimethyl ammonium bromide (CTAB) has been systematically studied. The phase ranges of vesicle and liquid crystal (LC) can be greatly extended with the addition of 1-hexanol. These specific structures distributed symmetrically on the two sides of the SDS/CTAB equimolar line in the pseudo ternary phase diagram. The aqueous two phase system (ATPS) contained vesicles that would transform into lamellar LC with the change of ratio of SDS/CTAB. The phase behaviors of SDS/CTAB system with addition of different alcohols (C5OH–C8OH) showed similar trends in structural transition except for phase span, demonstrating that the obstruction of electrostatic interaction between surfactant polar heads was affected by the insertion depth of the added alcohols.

Thermodynamic modeling of methane hydrate formation in the presence of imidazolium-based ionic liquids using two-step hydrate formation theory and CPA EoS

In this study, thermodynamic modeling is performed to predict the P-T equilibrium conditions of methane gas hydrate formation in presence of ionic liquids. The imidazolium-based ionic liquids including [EMIM][HSO4], [EMIM][EtSO4], [BMIM][BF4], [OH-EMIM][BF4], [BMIM][Cl] and [BMIM][Br] are modeled through two-step hydrate formation theory of Chen and Guo coupled with CPA EoS for calculating the fugacities of species in liquid and gas phase. The CPA pure component parameters for ionic liquids and also the majority of binary interaction parameters are adjusted using the liquid density and binary VLE data, respectively. The thermodynamic modeling is carried out in the presence of 0.1 weight fractions of all the studied imidazolium based ionic liquids. Moreover, the effect of three various concentrations of [BMIM][BF4] on the P-T equilibrium diagram of methane hydrate are predicted at 0.1, 0.15 and 0.20 weight fractions of this ionic liquid. The results indicate that the CPA EoS can satisfactorily model the phase behavior of aqueous solutions of imidazolium based ionic liquids considering 2B scheme for the association term. In addition, the results indicate good predictions of the proposed model for methane hydrate equilibrium conditions in the presence of imidazolium-based studied ionic liquids including concentration changes such that the absolute average deviations of methane hydrate formation pressures is obtained below 4.2%.

Effect of Additives on the Phase Behavior of SDS/CTAB/H2O Systems

Abstract The effect of additives on the phase behavior of aqueous solutions of sodium dodecyl sulfate (SDS) and cetyl trimethyl ammonium bromide (CTAB) has been studied in detail for extended applications. The results showed that both the widths of an anionic two-phase aqueous system (ATPSa) region with SDS in excess and a aqueous cationic two-phase system (ATPSc) region with CTAB in excess are very narrow, less than 1% in absence of any additives. However, phase regions of ATPS move toward the corresponding isotropic single phase regions and become wider in the presence of inorganic additives such as NaBr in the aqueous surfactant solutions. This is because the addition of inorganic salt increases the concentration of inorganic counter-ions and therefore the electrostatic interactions between counter-ions and surfactant aggregates. Meanwhile, the organic salts, sodium salicylate and tetrabutylammonium bromide, have been found to have a greater capacity to expand the range of ATPS because the electrostatic interactions between organic ions and aggregates were adjustable through the deformation of the electron cloud of organic ions. Organic additives with different properties can effectively extend the range of either ATPSc or ATPSa. Wherein, sodium salicylate can expand ATPSc efficiently and tetrabutylammonium bromide can expand ATPSa significantly.

Tuning Nanoparticle-Micelle Interactions and Resultant Phase Behavior.

The evolution of the interaction between an anionic nanoparticle and a nonionic surfactant and their resultant phase behavior in aqueous solution in the presence of electrolyte and ionic surfactants have been studied. The mixed system of anionic silica nanoparticles (Ludox LS30) with nonionic surfactant decaethylene glycol monododecylether (C12E10) forms a highly stable clear phase over a wide concentration range of surfactant. Small-angle neutron scattering (SANS) and dynamic light scattering data show that the surfactant micelles adsorb on the surface of the nanoparticle, resulting in micellar-decorated nanoparticle structures. With the addition of a small amount of electrolyte into this system, the stability gets disturbed substantially and turns to a two-phase (turbid) system. The evolution of interaction in this system has been examined, and it was found that micelle-induced long-range depletion attraction (modeled by a double Yukawa potential) between nanoparticles leads to their aggregation. Interestingly, the addition of anionic surfactant sodium dodecyl sulfate (SDS) in this two-phase system transforms it to a transparent one-phase state, suppressing the depletion-mediated aggregation of nanoparticles. This is attributed to the formation of anionic C12E10-SDS mixed micelles, and it is their repulsive micelle-micelle interaction that disrupts the depletion phenomenon. On the other hand, the addition of cationic surfactant dodecyl trimethylammonium bromide (DTAB) to the turbid LS30-C12E10 electrolyte system shows no change in the turbidity arising from an aggregated nanoparticle system. The driving interaction, in this case, is different from that of the surfactant-mediated depletion attraction; it is due to the attraction between the nanoparticles mediated by the presence of oppositely charged DTAB micelles between them, resulting in a charge-driven bridging aggregation of nanoparticles. Each of these multicomponent systems has been investigated using contrast variation SANS measurements for different contrast conditions where the role of individual components (nanoparticle or surfactant) in the mixed system has been selectively studied. These results thus show that nanoparticle-surfactant micelle interactions can be tuned by the presence of electrolyte and/or choice of surfactant combination.

Predictive approach for protein aggregation: Correlation of protein surface characteristics and conformational flexibility to protein aggregation propensity.

The aggregation of proteins became one of the major challenges in the development of biopharmaceu-ticals since the formation of aggregates can affect drug quality and immunogenicity. However, aggregation mechanisms are highly complex and the investigation requires cost, time, and material intensive experi-mental effort. In the present work, the predictive power of protein characteristics for the phase behavior of three different proteins which are very similar in size and structure was studied. In particular, the surface hydrophobicity, zeta potential, and conformational flexibility of human lysozyme, lysozyme from chicken egg white, and α-lactalbumin at pH 3, 5, 7, and 9 were assessed and examined for correlation with experimental stability studies focusing on protein phase behavior induced by sodium chloride and ammonium sulfate. The molecular dynamics (MD) simulation based study of the conformational flexibility without precipitants was able to identify highly flexible protein regions which could be associated to the less regular secondary structure elements and random coiled and terminal regions in particular. Conformational flex-ibility of the entire protein structure and protein surface hydrophobicity could be correlated to differing aggregation propensities among the studied proteins and could be identified to be applicable for predic-tion of protein phase behavior in aqueous solution without precipitants. For prediction of protein phase behavior and aggregation propensity in aqueous solution with precipitants, protein flexibility was further studied in dependency of salt concentration and species by means of human lysozyme. Even though the results of the salt dependent MD simulations could not be shown to be sufficient for prediction of salt depending phase behavior, this study revealed a more pronounced destabilizing effect of ammonium sulfate in comparison to sodium chloride and thus, was found to be in good agreement with theoretical considerations along the Hofmeister series as well as experimentally evaluated phase behavior. Biotechnol. Bioeng. 2017;114: 1170-1183. © 2016 Wiley Periodicals, Inc.

Heat capacity and phase behaviour of aqueous solutions of triethylene glycol monopentyl ether. Two point scaling analysis

The specific heat capacities of triethylene glycol monopentyl ether aqueous solutions have been measured from 278.15 to 338.15 K, over the wide concentration range by DSC. The apparent and partial molar heat capacities were calculated and the two-point scaling theory was used to analyze these data. Obtained results were discussed in terms of aggregation taking place in the solution and influence of the temperature on this process. The separation line between single-phase solution and two-phase system was determined using scanning calorimetry.

Cation-Induced Hydration Effects Cause Lower Critical Solution Temperature Behavior in Protein Solutions.

The phase behavior of protein solutions is important for numerous phenomena in biology and soft matter. We report a lower critical solution temperature (LCST) phase behavior of aqueous solutions of a globular protein induced by multivalent metal ions around physiological temperatures. The LCST behavior manifests itself via a liquid-liquid phase separation of the protein-salt solution upon heating. Isothermal titration calorimetry and zeta-potential measurements indicate that here cation-protein binding is an endothermic, entropy-driven process. We offer a mechanistic explanation of the LCST. First, cations bind to protein surface groups driven by entropy changes of hydration water. Second, the bound cations bridge to other protein molecules, inducing an entropy-driven attraction causing the LCST. Our findings have general implications for condensation, LCST, and hydration behavior of (bio)polymer solutions as well as the understanding of biological effects of (heavy) metal ions and their hydration.

Phase diagram of mixtures of colloids and polymers in the thermal crossover from good to θ solvent.

We determine the phase diagram of mixtures of spherical colloids and neutral nonadsorbing polymers in the thermal crossover region between the θ point and the good-solvent regime. We use the generalized free-volume theory, which takes into account the polymer-concentration dependence of the depletion thickness and of the polymer compressibility. This approach turns out to be quite accurate as long as q = Rg/Rc ≲ 1 (Rg is the radius of gyration of the polymer and Rc is the colloid radius). We find that, close to the θ point, the phase diagram is not very sensitive to solvent quality, while, close to the good-solvent region, changes of the solvent quality modify significantly the position of the critical point and of the binodals. We also analyze the phase behavior of aqueous solutions of charged colloids and polymers, using the approach proposed by Fortini et al. [J. Phys.: Condens. Matter 17, 7783 (2005)].

A new hydrogen bonding local composition based model in obtaining phase behavior of aqueous solutions of sugars

In this research, the local composition based model proposed by Pazuki et al. is developed to consider the hydrogen bonding effect by using the molecular surface area parameter. The proposed model has two terms which account for the combinatorial and residual effects. The Freed-FV model is used for the combinatorial term while the model proposed by Pazuki et al. is developed for the residual term along with hydrogen bonding effects. The interaction parameters of the model are obtained from the experimental data of water activity. Also, the model is used to correlate and predict thermophysical properties of aqueous sugar solutions (glucose, sucrose, fructose, maltose, mannose, maltotriose, xylose and galactose) such as water activity, density, solubility, osmotic coefficient, vapor pressure and boiling point. A comparison between the results obtained from the model and UNIQUAC model shows that the proposed model can successfully predict thermophysical properties of sugar–water systems in various conditions.

Amphiphilic copolymers of sucrose methacrylate and acrylic monomers: Bio-based materials from renewable resource

Regioselective sucrose 1′-O-methacrylate obtained by transesterification catalyzed by Proteinase-N was copolymerized with hydrophilic N-isopropylacrylamide and hydrophobic methyl methacrylate in different molar ratios by free radical polymerization. The copolymers were characterized by 13C nuclear magnetic resonance spectroscopy, gel permeation chromatography, differential scanning calorimetry and thermogravimetry. Solubility and phase behavior of aqueous solutions were also investigated. The glass transition of the copolymers presents a positive deviation from the values of the homopolymers due to the high density of inter and intramolecular hydrogen bonding. Their solubility is strongly dependent on the composition. Copolymers poor in methyl methacrylate are water soluble, while copolymers richer in methyl methacrylate behaves as hydrogel. These hydrogels are not chemically crosslinked and their form can be design prior swelling by the conventional processing methods, such as solvent casting and extrusion for instance. Copolymers of N-isopropylacrylamide are water soluble and their aqueous solutions present a lower critical solution temperature behavior forming thermoreversible hydrogels.

“Schizophrenic” Hemocompatible Copolymers via Switchable Thermoresponsive Transition of Nonionic/Zwitterionic Block Self-Assembly in Human Blood

"Schizophrenic" diblock copolymers containing nonionic and zwitterionic blocks were prepared with well-controlled molecular weights via atom-transfer radical polymerization (ATRP). In this work, we report a systematic study of how morphological changes of poly(N-isopropylacrylamide)-block-poly(sulfobetaine methacrylate) (PNIPAAm-b-PSBMA) copolymers affect hemocompatibility in human blood solution. The "schizophrenic" behavior of PNIPAAm-b-PSBMA was observed by (1)H NMR, dynamic light scattering (DLS), and turbidity measurement with double morphological transition, exhibiting both lower critical solution temperature (LCST) and upper critical solution temperature (UCST) in aqueous solution. Below the UCST of PSBMA block, micelles were obtained with a core of insoluble PSBMA association and a shell of soluble PNIPAAm, whereas the opposite micelle structure was observed above the LCST of PNIPAAm block. In between the UCST and LCST, unimers with both soluble blocks were detected. Hydrodynamic size of prepared polymers and copolymers is determined to illustrate the correlations between intermolecular nonionic/zwitterionic associations and blood compatibility of PNIPAAm, PNIPAAm-b-PSBMA, and PSBMA suspension in human blood. Human fibrinogen adsorption onto the PNIPAAm-b-PSBMA copolymers from single-protein solutions was measured by DLS to determine the nonfouling stability of copolymer suspension. The new nonfouling nature of PNIPAAm-b-PSBMA copolymers was demonstrated to show extremely high anticoagulant activity and antihemolytic activity in human blood over a wide range of explored temperatures from 4 to 40 °C. The temperature-independent blood compatibility of nonionic/zwitterionic block copolymer along with their schizophrenic phase behavior in aqueous solution suggests their potential in blood-contacting applications.