Association In Aqueous Solutions Research Articles

Entropy Drives Interpolymer Association in Water: Insights into Molecular Mechanisms.

Interpolymer association in aqueous solutions is essential for many industrial processes, new materials design, and the biochemistry of life. However, our understanding of the association mechanism is limited. Classical theories do not provide molecular details, creating a need for detailed mechanistic insights. This work consolidates previous literature with complementary isothermal titration calorimetry (ITC) measurements and molecular dynamics (MD) simulations to investigate molecular mechanisms to provide such insights. The large body of ITC data shows that intermolecular bonds, such as ionic or hydrogen bonds, cannot drive association. Instead, polymer association is entropy-driven due to the reorganization of water and ions. We propose a unifying entropy-driven association mechanism by generalizing previously suggested polyion association principles to include nonionic polymers, here termed polydipoles. In this mechanism, complementary charge densities of the polymers are the common denominators of association, for both polyions and polydipoles. The association of the polymers results mainly from two processes: charge exchange and amphiphilic association. MD simulations indicate that the amphiphilic assembly alone is enough for the initial association. Our proposed mechanism is a step toward a molecular understanding of the formation of complexes between synthetic and biological polymers under ambient or biological conditions.

The characteristics and flocculation performance of hydrophobic association poly‐(3‐methacryloylamido propyl trimethyl ammonium chloride)

AbstractThe cationic polymer plays a crucial role in the flocculation process for solid–liquid separation. A hydrophobic‐associated cationic polymer was prepared through micellar free‐radical polymerization of cationic monomer 3‐methyl acrylamide propyl trimethyl ammonium chloride (MAPTAC) and hydrophobic monomer Poly (ethylene glycol) Octadecyl methacrylate (OEMA). The Poly‐MAPTAC‐OEMA can form network structure through intermolecular hydrophobic association in aqueous solution, which leads to the solution viscosity increase and the salt thickening property. The critical associating concentrations (CACs) of Poly‐MAPTAC‐OEMA are 5818–6992 mg/L in aqueous solution. For the diatomite suspensions, at the dosage above about 5 mg/L, the Poly‐MAPTAC‐OEMA can show higher flocculation efficiency compared with Poly‐MAPTAC. Specifically, at the dosage of 8 mg/L, the enhancement rate of sedimentation rate can reach 7.27%–32.31%. Meanwhile, the hydrophobic association mainly enhances the bridging ability but has no significant effect on the improvement of the electric neutralization ability of Poly‐MAPTAC‐OEMA. The flocculation performance‐enhanced dosage of Poly‐MAPTAC‐OEMA is obviously lower than the CAC of Poly‐MAPTAC‐OEMA; this may be because during the flocculation process, the Poly‐MAPTAC‐OEMA first absorb and deeply concentrate on the particle surface, and then the hydrophobic association and bridging enhancement of Poly‐MAPTAC‐OEMA can occur more easily on the particle surface.

Ion hydration and association in aqueous solutions of zinc sulfate by dielectric spectroscopy

Aqueous solutions of zinc sulfate, ZnSO4(aq), have been studied at 25°C by dielectric relaxation spectroscopy (DRS) over the frequency range 0.2≤ν/GHz≤89 at concentrations 0.04≲c/mol L−1≲2.4. The spectra obtained could be accounted for mostly by the presence of four Debye processes (a 4D model). These processes consisted of two solvent-related modes at higher frequencies plus two solute-related modes at lower frequencies. At low solute concentrations (c≤0.34molL−1) it was necessary to include an additional small amplitude mode which was thought to be due to ion-cloud relaxation (a (D) + 4D model). While the DR spectra for ZnSO4(aq) were broadly similar to those of other divalent metal sulfate solutions there were also differences. In particular, no evidence was found for the significant formation of double-solvent-separated ion pairs (2SIP). Further, the mode centered around 8 GHz, which for similar systems is usually assigned to the presence of contact ion pairs (CIPs), appears to be an unresolved mixture of contributions from CIPs and dynamically-retarded (‘slow’) water molecules. Analysis of the solvent-related modes indicated that the free ions (Zn2+(aq) and SO42−(aq)) and the ion pairs (SIPs and CIPs) were strongly hydrated. The decline in their effective hydration numbers (Z values) with increasing c is common and is thought to result from ion/IP interactions. The overall association constant for the ion pairs was found to be consistent with literature data.

Simple Coacervation of Guanidinium-Containing Polymers Induced by Monovalent Salt

Liquid–liquid phase separation (LLPS) of macromolecules, called coacervation, is induced by non-covalent intermolecular associations in aqueous solutions, which is frequently observed in biological processes including cellular compartmentation, signaling, and regulation. Recently, associative interactions between π-conjugated residues have emerged to induce LLPS, along with electrostatic interaction. An arginine residue having a positively charged guanidinium group plays a pivotal role in protein phase behavior because the orientational amphiphilicity of guanidinium groups allows face-to-face π–π stacking despite Coulombic repulsion. In this study, we investigate the simple coacervates of guanidinium-functionalized polyelectrolytes (i.e., poly-arginine) in aqueous media as a function of salt concentration, salt type, and temperature to understand the exclusive role of π-conjugated moieties. Contrary to ammonium-functionalized polyelectrolyte (i.e., poly-lysine) solutions, guanidinium-functionalized polyelectrolyte solutions become turbid by adding monovalent salts and exhibit the upper critical solution temperature (UCST) behavior; the critical temperature is harnessed by salt concentration and salt type. Although a π–π stacked guanidinium pair can exist at a lower salt concentration, LLPS occurs when the number of intermolecular guanidinium pairs goes beyond a critical value to produce the network structure. Furthermore, the enthalpically favored π–π interaction directly affects the bulk rheological behavior and the interfacial property of the coacervates. Our findings provide insights into the underlying interactions of protein phase separation and shed new light on the critical role of π–π stacking in the biological process and material design.

Molecular Dynamics Simulation of Association Processes in Aqueous Solutions of Maleate Salts of Drug-like Compounds: The Role of Counterion.

The study of the formation of microstructures during the interaction of a protonated drug-like compound (API) with a maleic acid monoanion sheds light on the assembly processes in an aqueous solution at the molecular level. Molecular dynamics (MD) simulations coupled with density functional theory (DFT) calculations made it possible to find initial hydrogen bonding motifs during the assembly process, leading to the formation of heterodimers and trimers. The process of trimer formation [protonated API—maleic acid monoanion—protonated API] proceeds through the formation of three intermolecular H-bonds by the CO2− group of the maleic acid monoanion in both systems. The total enthalpy/energy of these H-bonds is more than 70 kJ/mol. Thus, the maleic acid monoanion plays a key role in the processes of association in aqueous solution, and the interaction of the maleic acid monoanion with API is more preferable than the interaction of API molecules with each other. DFT computations in the discrete continuum approximation reveal the spectral features of heterodimers and trimers, and the ATR-IR spectra confirmed these findings. MD simulations followed by DFT calculations made it possible to describe the initial stages of the formation of pharmaceutical cocrystals in an aqueous solution.

Fluorescence Study of the Influence of the Structure and Hydrophobicity of Fluorescent Dyes and Cationic Surfactants on their Association in Aqueous Solutions

The statistical characteristics of the dependences of the fluorescence signal of analytical systems as a function of the integral parameters of the structure of fluorescent reagents and cationic surfactants on their association in aqueous solutions has been investigated. Molecular weight, surface area, and their first-order molecular connectivity index have been taken as parameters of the structure of the reagents and cationic surfactants. The influence of the hydrophobicity of the reagent and cationic surfactants, such as the octanol–water distribution constant and octanol–water partition coefficient, on the fluorescence signal of the reagent–cationic surfactant associates have also been investigated. It is shown that the associates of anionic reagents with cationic surfactant counter ions are characterised by high stability and a higher analytical signal compared with associates in which there is no electrostatic attraction between the reagent and the surfactant ion. The effect of hydrophobicity of the reagent and cationic surfactant in the absence of electrostatic attraction between the interacting particles is similar. The increase in the role of the influence of the structure of cationic reagents in their association with cationic surfactants, when the electrostatic attraction is absent and the stability of the associates is due mainly to hydrophobic interactions, is noticeable. The regularities of the influence of the colloid-chemical state on the analytical signal of associated cationic surfactants in solutions have been investigated. The study made it possible to formulate a rational basis for the search and design of analytical systems for the determination of large cations by the fluorescence method.

Molecular insight on ion hydration and association in aqueous choline chloride solutions

The biogenic choline cation (Ch+) is an essential nutrient for humans and many animals. Its interactions with water and other ions are often crucial for various biochemical processes running in living organisms. Nevertheless, the available information on the features of these interactions is rather scarce. In this paper we present the molecular details of ion hydration and association in water for choline chloride (ChCl) as one of the representatives of choline-based ionic compounds. The features of these processes were studied over a solute concentration range up to 1.6 M using the integral equation method in 1D- and 3D-RISM approaches. Analysis of the obtained data revealed that Ch+ has a spacious, loose hydration shell with large total hydration number. Moreover, as found, only –OH group of Ch+ is able to form H-bonds with solvent. An increasing of solute concentration leads to an appropriate dehydration of both ions and weakening of their H-bonding with water. According to the presented results, the Ch+-Cl− association in aqueous solutions is possible by two ways, namely, via the onium moiety by Coulomb interaction or via hydroxyl group by H-bonding. However, the ion binding way depends on the solute concentration. The presented data add new knowledge on the behavior of this compound in biological media.

A New Approach for Improving the Antibacterial and Tumor Cytotoxic Activities of Pipemidic Acid by Including It in Trimethyl-β-cyclodextrin.

Pipemidic acid (HPPA) is a quinolone antibacterial agent used mostly to treat gram-negative infections of the urinary tract, but its therapeutic use is limited because of its low solubility. Thus, to improve drug solubility, natural cyclodextrins (CDs) are used for their ability of including guest molecules within their cavities. The aim of this work was to evaluate the antibacterial activity and the preliminary anticancer activity of HPPA included into Heptakis (2,3,6-tri-O-methyl)-β-cyclodextrin (TRIMEB) as a possible approach for a new innovative formulation. The inclusion complex of HPPA with TRIMEB was prepared in solid state by the kneading method and confirmed by FT-IR and powered X-ray diffraction. The association in aqueous solutions of pipemidic acid with TRIMEB was investigated by UV-Vis spectroscopy. Job’s plots have been drawn by UV-visible spectroscopy to confirm the 1:1 stoichiometry of the host–guest assembly. The antibacterial activity of HPPA, TRIMEB and of their complex was tested on Escherichia coli, Pseudomonas aeruginosa, and Staphilococcus aureus. The complex was able to increase 47.36% of the median antibacterial activity of the free HPPA against E. coli (IC50 = 249 µM vs. 473 µM). Furthermore, these samples were tested on HepG-2 and MCF-7. After 72 h, the median tumoral cytotoxicity exerted by the complex was increased by 78.08% and 94.27% for HepG-2 and MCF-7 respectively, showing a stronger bioactivity of the complex than the single HAPPA.

Understanding of Structure and Thermodynamics of Melamine Association in Aqueous Solution from a Unified Theoretical and Experimental Approach.

The aggregation propensity of melamine molecules in aqueous solutions in a range of melamine concentrations is investigated by means of a combination of theoretical and experimental approaches. It is observed that the hydrogen bonding interactions of sp3 nitrogen atoms of one melamine with sp2 nitrogen atoms of another melamine play a major role in the melamine association. This finding is complemented by the observed favorable electrostatic energies between melamine molecules. The estimation of the orientational probability of melamine aromatic ring rules out any role of π-π interaction in melamine association. Further, the quantum chemical calculations suggest that a melamine molecule prefers to bind with another like molecule with a dihedral angle ranging from 36° to 46°. We have also determined the dimer existence autocorrelation functions to investigate the melamine-dimer stability with time in aqueous solution. Our results are well validated by the experimental findings (Chapman, R. P.; Averell, P. R.; Harris, R. R. Solubility of Melamine in Water. Ind. Eng. Chem. 1943, 35, 137-138. Ahromi, A. J.; Moosheimer, U. Oxygen Barrier Coatings Based on Supramolecular Assembly of Melamine. Macromolecules 2000, 33, 7582-7587. Yang, C.; Liu. Y. Studying on the Steady-State and Time-Resolved Fluorescence Characteristics of Melamine. Spectrochim. Acta A 2010, 75, 1329-1332. Mircescu, N. E.; Oltean, M.; Chis, V.; Leopold, N. FTIR, FT-Raman, SERS and DFT study on Melamine. Vib. Spectrosc. 2012, 62, 165-171. Makowski. S. J.; Lacher. M.; Schnick. W. Supramolecular Hydrogenbonded Structures between Melamine and N-Heterocycles. J. Mol. Struct. 2012, 1013, 19-25. Li, Z.; Chen, G.; Xu, Y.; Wang, X.; Wang, Z. Study of the Structural and Spectral Characteristics of C3N3(NH2)3(n = 1-4) Clusters. J. Phys. Chem. A 2013, 117, 12511-12518. Li, P.; Arman, D. H.; Wang, H.; Weng, L.; Alfooty, K.; Angawi, R. F.; Chen. B. Solvent Dependent Structures of Melamine: Porous or Non-porous. Cryst. Growth Des. 2015, 15, 1871-1875. Chen, J.; Lei, X.; Peng, B. Study on the Fluorescence Spectra of Melamine in Pure Milk. J. Opt. 2017, 46, 183-186.). Moreover, the thermodynamics of melamine association reveals that the association process is essentially driven by enthalpy, and this enthalpy-driven phenomenon is also confirmed by the experimental isothermal titration calorimetry measurements.

Driving Forces for Oppositely Charged Polyion Association in Aqueous Solutions: Enthalpic, Entropic, but Not Electrostatic.

Driving forces for association between oppositely charged biological or synthetic polymers in aqueous solution have long been identified as electrostatic in origin. This attraction is broken down into an entropic component, due to loss of counterions, and an enthalpic component, stemming from Coulombic attraction between opposite charges. While the balance between entropic and enthalpic contributions shifts according to the conditions, the presence of exotherms or endotherms on mixing, though small, are viewed as signatures of Coulombic interactions which support theories of polyelectrolyte association rooted in continuum electrostatics. Here, a head-to-head comparison is made between mechanisms based on electrostatics and those based on specific ion pairing, or ion exchange. Using a Hofmeister series of counterions for a common polycation, poly(diallyldimethylammonium), enthalpy changes on association with poly(styrenesulfonate) are shown to derive from changes in water perturbation, revealed by Raman scattering studies of water O-H vibrations. The free energy for complexation is almost completely entropic over all salt concentrations.

Thermal fluctuations enable rapid protein–protein associations in aqueous solution by lowering the reaction barrier

In hydrophilic protein–protein associations, the dehydration penalty, which can cause the formation of a reaction barrier, must be canceled out; however, its mechanism has not been clarified. Here, we explored the possible mechanism through investigation of the dimerization of nucleotide binding domains (NBDs). We assessed the different dimerization processes by molecular dynamics simulations with and without thermal fluctuations in each NBD. Consequently, the reaction barriers of the former and latter were estimated to be ∼100 and ∼15kcal/mol, respectively, suggesting that thermal fluctuations in the proteins facilitate the exclusion of water molecules from the interfacial region, thereby lowering the barrier.

Recognition and sequestration of ω-fatty acids by a cavitand receptor

One of the largest driving forces for molecular association in aqueous solution is the hydrophobic effect, and many synthetic receptors with hydrophobic interiors have been devised for molecular recognition studies in water. Attempts to create the longer, narrower cavities appropriate for long-chain fatty acids have been thwarted by solvophobic collapse of the synthetic receptors, giving structures that have no internal spaces. The collapse generally involves the stacking of aromatic panels onto themselves. We describe here the synthesis and application of a deep cavitand receptor featuring "prestacked" aromatic panels at the upper rim of the binding pocket. The cavitand remains open and readily sequesters biologically relevant long-chain molecules-unsaturated ω-3, -6, and -9 fatty acids and derivatives such as anandamide-from aqueous media. The cavitand exists in isomeric forms with different stacking geometries and n-alkanes were used to characterize the binding modes and conformational properties. Long alkyl chains are accommodated in inverted J-shaped conformations. An analogous cavitand with electron-rich aromatic walls was prepared and comparative binding experiments indicated the role of intramolecular stacking in the binding properties of these deep container molecules.

Ion association in aqueous solution

The properties of aqueous ionic solutions are determined by strong electrostatic interactions, which are influenced by polarizability and charge transfer interactions. Potential models which include polarizability and charge transfer have been developed for water and single ion properties. Here, the ion–ion interactions are optimized so that the osmotic pressure as a function of concentration is reproduced. Using the optimized potentials, the amount of ion pairing and larger cluster formation is calculated. For NaCl, NaI, and KCl, there is a small amount of pairing, with larger clusters present as well. For KI, there is much more pairing and much larger clusters are observed. The amount of pairing is consistent with the law of matching affinities, with the pairs that show the least pairing also being the most mis-matched in terms of size or solvation free energy. The charge transfered from the anions to water is more than from is transferred from the water to cations, so the water molecules acquire a negative charge, which increases with ion concentration.

Ion hydration and association in aqueous potassium phosphate solutions.

Ionic hydration and ion association in aqueous solutions of KH2PO4, K2HPO4, and K3PO4 at 25 °C up to high concentrations have been investigated using dielectric relaxation spectroscopy (DRS). The three phosphate anions were found to be extensively hydrated, with total hydration numbers at infinite dilution of ~11 (for H2PO4(-)), ~20 (HPO4(2-)), and ~39 (PO4(3-)). These values are indicative of the existence of a second hydration shell around HPO4(2-) and especially PO4(3-). Two types of hydrating water molecules could be quantified: irrotationally bound (ib, H2O molecules essentially "frozen" on the DRS time scale) and "slow" (loosely bound water molecules with identifiably slower dynamics than bulk water). For H2PO4(-) over the entire concentration range and for HPO4(2-) and PO4(3-) at concentrations c ≲ 1 mol L(-1), only "slow" H2O was detected; however, at higher concentrations of the latter two anions, an increasing fraction of ib water appears, making up ~50% of the total hydration number close to the saturation limit of K2HPO4. Contrary to common belief, all three salts showed significant ion pair formation, with standard association constants of the 1:1 species increasing in the order: KH2PO4(0)(aq) < KHPO4(-)(aq) < KPO4(2-)(aq). The main type of ion pair in solution shifted from solvent-shared ion pairs (SIPs) to double-solvent-separated ion pairs (2SIPs) in the same sequence.

Iodine-water-alkanol and potassium iodide-water-alkanol systems: Phase diagrams and regularities of association according to IR and NMR spectroscopic data

The variation of the iodine and potassium iodide solubilities in water-monoatomic alcohol (ethanol, propanol, isopropanol) solvents is considered from the standpoint of IR spectroscopic and chemometric data on association in water-alkanol binary mixtures. The iodine and potassium iodide solubilities in the mixed solvents vary nonlinearly with solvent composition because of the formation of 1 : 1 and 1 : 3 water-alcohol heteroassociates and alcohol homoassociates. Different kinds of phase diagram are observed for the iodine-water-alcohol systems: the I2-H2O-1-C3H7OH and the I2-H2O-2-C3H7OH diagrams have a phase separation region, while the I2-H2O-C2H5OH diagram does not. This fact is explained in terms of the interaction between the components of the systems. The variation of the potassium iodide solubility in the mixed solvent is discussed: a decrease in the KI solubility is symbatic to an increase in the relative concentration of 1 : 1 associates in the water-alcohol solution. The run of the iodine and potassium iodide solubility curves at low alcohol concentrations is explained on the basis of NMR spectroscopic data on association in aqueous solutions of the monoatomic alcohols.

A study of n-dodecylammonium acrylamido-2-methylpropanesulfonate association in aqueous solutions

Association of a micelle-forming monomer, n-dodecylammonium 2-acrylamido-2-methylpropanesulfonate, in aqueous solutions has been studied in a concentration range of 1.5 × 10−3–2.5 × 10−1 M with the use of conductometry, capillary and rotational viscometry, isothermal translational diffusion, and atomic force microscopy. Two critical micelle concentrations have been determined, and the shape of n-dodecylammonium 2-acrylamido-2-methylpropanesulfonate micelles has been proposed.

Stabilization of a Cl––Cl– Anion Pair in the Gas Phase: Ab Initio Microsolvation Study

Despite the confirmation of Cl(-)-Cl(-) association in aqueous solution and crystalline state, there have been no reports about the existence of stable dichloride anion pair in the gas phase. In the current work we performed a systematic ab initio study of microsolvation of dichloride anion pair. The stepwise solvation mechanism observed for free gaseous [Cl2(H2O)n](2-) (n = 2-10) clusters was found to be quite interesting. The lowest structure for dichloride hexahydrate closely resembles cubic water octamer W8 in which two water molecules in the corners of the cube are substituted by two chloride anions. We have also shown that Cl(-)-Cl(-) pair may be completely stabilized by about 36 water molecules in the gas phase. Stabilization of the pair leads to the formation of cyclic H2O structures that bridge the Cl(-) ions. It has been predicted that the large clusters of [Cl2(H2O)36](2-) and [Cl2(H2O)40](2-) may exhibit properties analogous to bulk aqueous solutions, therefore they could become good molecular models for understanding complicated processes of solvation of Cl(-) in the bulk.

Pairing Mechanism among Ionic Liquid Ions in Aqueous Solutions: A Molecular Dynamics Study

In this study, we carried out molecular dynamics simulations to examine the molecular mechanism for ionic liquid pair association in aqueous solutions. We chose the commonly studied imidazolium-based ionic liquid pairs. We computed potentials of mean force (PMF) for four systems: 1,3-dimethlylimidazoliumchloride, 1,3-dimethlylimidazolium iodide, 1-methly-3-octylimidazolium chloride, and 1-methly-3-octylimidazolium iodide. Our PMF studies show a stronger interaction for the ion pairs of systems involving dimethlylimidazolium as the cation species compared with that of the systems containing octylimidazolium. This result indicates a decrease in ion-pair association as the cation alkyl tail length increases. We also studied the kinetics of ion-pair dissociation using different rate theories such as the Grote-Hynes and Kramer's theories. As expected, the computed rate results significantly deviated from results obtained from transition state theory because it does not account for dynamical solvent effects. Dissociative barrier curvatures are found to be very small for the systems investigated because the transmission coefficients computed using Grote-Hynes theory and Kramer's theory are approximately equal. Our analysis of the rotational dynamics of cations revealed that the time scales for molecular reorientation are longer for cations with longer alkyl tails.

Fluorimetric study of the mechanism of molecular association in aqueous solutions of polymethacrylic acid and sodium dodecylbenzenesulfonate

Fluorescent spectroscopy is used to investigate the processes of intermolecular association in mixed solutions of polymethacrylic acid (PMAA) and anionic sodium dodecylbenzenesulfonate (SDBS). We propose a model for describing the stage-by-stage mechanism of association processes and conclude that the nature of intermolecular associates depends on the PMAA-SDBS concentration ratio in the solution. Studying the kinetics of fluorescence decay reveals the simultaneous existence of two types of formations capable of pyrene solubilization.

A Conductance Study of Guanidinium Chloride, Thiocyanate, Sulfate, and Carbonate in Dilute Aqueous Solutions: Ion-Association and Carbonate Hydrolysis Effects

We study the conductance of dilute aqueous solutions for a series of guandinium salts at 298.15 K. The experimental molar conductivities were analyzed within the framework of the Quint-Viallard theory in combination with Debye-Hückel activity coefficients. From this analysis, we find no evidence for significant ion association in aqueous solutions of guanidinium chloride (GdmCl) and guanidinium thiocyanate (GdmSCN), and the molar conductivity of these electrolytes can be modeled assuming a complete dissociation. The limiting ionic conductivity of the guanidinium ion (Gdm(+)) is accurately determined to λ(Gdm(+)) = 51.45 ± 0.10 S cm(2) mol(-1). For the bivalent salts guanidinium sulfate (Gdm(2)SO(4)) and guanidinium carbonate (Gdm(2)CO(3)), the molar conductivities show small deviations from ideal (fully dissociated electrolyte) behavior, which are related to weak ion association in solution. Furthermore, for solutions of Gdm(2)CO(3), the hydrolysis of the carbonate anion leads to distinctively increased molar conductivities at high dilutions. The observed ion association is rather weak for all studied electrolytes and cannot explain the different protein denaturing activities of the studied guanidinium salts, as has been proposed previously.