Hydrophobic Hydration Research Articles

Hydrophobic Effect of Alkyl Groups Stabilizing Self-Assembled Colloids in Water.

Self-assembling behavior of hydrophobic molecules in water confirms that the hydrophobic effect (HE) of alkyl groups stabilizes the aqueous colloids. Fe(CO){CO(CH2)n-1CH3}(Cp)(PPh3) molecules (FpCn) with a Fp head and alkyl tail are water-insoluble. FpC1 aggregates in water precipitated in hours, whereas the hydrophobic interaction (HI) of long alkyl groups drove FpCn (n = 6-18) molecules assemble into colloids in water. The alkyl tails interacted and stretched as indicated by IR analysis, while the separation of Fp head groups at the surface of colloids was indicated by the redox behavior of Fe elements. The molecules therefore arranged into a proposed "Y" shape with hydration cavities. The IR and cyclic voltammetry (CV) analyses indicated that the longer the alkyl tail, the larger the hydration cavity and the stronger the HI. Both HI and hydrophobic hydration (HH) were identified as the HE stabilizing the colloids in water. This knowledge is applicable for a broad range of disciplines, including biology, chemistry, and material science.

Water structure around hydrophobic amino acid side chain analogs using different water models.

The water structure around hydrophobic groups governs various biochemical processes. There is an ongoing debate on whether water molecules near hydrophobic groups are more ordered with greater participation in water-water hydrogen bonding with respect to water in the pure bulk state. The water structure around six different hydrophobic amino acid side chain analog molecules has been studied in pure water using molecular dynamics simulations. The analysis of water tetrahedral order parameter and the number of hydrogen bonds formed by the individual water molecules in the first hydration shell of the hydrophobic analogs provide evidence that both ordering and hydrogen bonds involving water molecules are to some extent reduced in the hydrophobic hydration shell. It is revealed that the water tetrahedrality in the outer part of the first hydrophobic hydration shell is equivalent to bulk water for all the water models except for the TIP4P-2005 model which shows marginally higher tetrahedrality. However, irrespective of the model employed, water tetrahedrality has always been found to be reduced in the inner part of the first hydration shell, which eventually makes the overall water tetrahedrality in the first hydrophobic hydration shell marginally lower than that observed for pure bulk water. Importantly, it is noticed that the decrease in water structuring exhibits solute size dependencies. Around a small solute like methane, the water tetrahedral ordering or hydrogen bonding propensity is quite similar to that of the bulk state. The effect, reduction in water structuring, is however more pronounced for relatively larger solutes.

Preferential solvation of rosmarinic acid in binary solvent mixtures of ethanol + water and methanol + water according to the inverse Kirkwood–Buff integrals method

The preferential solvation parameters (δx1,3) of rosmarinic acid in binary solvent mixtures of ethanol+water and methanol+water were derived from their thermodynamic properties by means of the inverse Kirkwood–Buff integrals method. δx1,3 was negative in water-rich mixtures but positive in solvent compositions from 0.20 or 0.24 to 1 in mole fraction of methanol or ethanol, respectively. It was conjecturable that in water-rich mixtures, the hydrophobic hydration around the nonpolar aromatic groups of rosmarinic acid played a relevant role in the solvation. The higher solvation by methanol or ethanol in mixtures of similar co-solvent compositions could be mainly due to polarity effects. The preference of rosmarinic acid in intermediate compositions and in methanol-rich or ethanol-rich mixtures could be explained in terms of the higher acidic behavior of rosmarinic acid molecules interacting with the hydrogen acceptor groups in methanol or ethanol. The calculations were required in the pharmaceutical and chemical industries to save time and money in the optimization of the solubilization and/or crystallization process designs.

Solubility modelling and preferential solvation of paclobutrazol in co-solvent mixtures of (ethanol, n-propanol and 1,4-dioxane) + water

The equilibrium solubility of paclobutrazol in co-solvent mixtures of ethanol (1)+water (2), n-propanol (1)+water (2) and 1,4-dioxane (1)+water (2) were determined experimentally by using isothermal dissolution equilibrium method within the temperature range from (278.15 to 313.15)K under atmospheric pressure (101.1kPa). At the same temperature and mass fraction of co-solvent, the mole fraction solubility of paclobutrazol in the three binary co-solvent mixtures obeyed the following order from high to low: 1,4-dioxane (1)+water (2)>n-propanol (1)+water (2)>ethanol (1)+water (2). The preferential solvation parameters were derived from their thermodynamic solution properties by means of the inverse Kirkwood–Buff integrals. The preferential solvation parameters for ethanol, n-propanol or 1,4-dioxane (δx1,3) were negative in water-rich mixtures but positive in compositions from 0.24 (0.19, 0.18) in mole fraction of ethanol (n-propanol or 1,4-dioxane) to pure ethanol (n-propanol or 1,4-dioxane). The preferential solvation magnitude of paclobutrazol by the co-solvent was highest in ethanol (1)+water (2) mixtures and lowest in n-propanol (1)+water (2). It was conjecturable that in the former case hydrophobic hydration around the aromatic rings played the main role in the drug’s solvation. The higher solvation by ethanol (n-propanol or 1,4-dioxane) in intermediate compositions and in colsolvent-rich mixtures could be explained in terms of the higher basic behaviour of this co-solvent interacting with the Lewis acidic groups of the paclobutrazol. Besides, the drugs’ solubilities were mathematically represented by using the Jouyban-Acree model, van’t Hoff-Jouyban-Acree model and Apelblat-Jouyban-Acree model obtaining average relative deviations lower than 4.73% for correlative studies.

Thermodynamics of the Thermal Denaturation of Acid Molten Globule State of Cytochrome c Indicate a Reversible High-Temperature Oligomerization Process.

In this study, we performed differential scanning calorimetry (DSC) and pressure perturbation calorimetry (PPC) analysis of the thermal transition of cytochrome c from an acidic molten globule (MG) state with the protein concentrations of 0.5-18.2 mg/mL. DSC profiles were highly reversible and showed clear protein-concentration dependence, indicating that reversible oligomerization occurred accompanying the thermal transition from the MG state. The DSC and PPC data required at least a six-state model (MG1 ⇄ MG2 ⇄ D ⇄ 1/2 I2 ⇄ 1/3 I3 ⇄ 1/4 I4) including three new oligomeric states: dimer (I2), trimer (I3), and tetramer (I4) in addition to the three monomeric states previously characterized. Dynamic light scattering confirmed the oligomerization during the thermal transition. The partial specific volumes of these oligomeric states were found to be smaller than those of the monomeric states, MG2 and D, indicating dehydration of hydrophobic surface or hydration of released anions may occur with the reversible oligomerization.

Molecular Aggregation in Binary Mixtures of Pyrrolidine, N-Methylpyrrolidine, Piperidine, and N-Methylpiperidine with Water: Thermodynamic, SANS, and Theoretical Studies.

Piperidine and N-methylpiperidine hydrates aggregate in liquid aqueous solutions due to hydrogen bonds between hydration water molecules. No such effects occur in the mixtures of the amines with methanol, that supports the idea of active role of water solvent in the aggregation. However, the question of contributions in thermodynamic functions due to specific interactions, van der Waals forces, and the size and shape of the molecules remains open. In the present study, limiting partial molar enthalpies of solution of pyrrolidine, N-methylpyrrolidine, piperidine, and N-methylpiperidine in water and methanol and vice versa were measured and compared with those assessed from theoretically calculated molecular interaction energies using a simple "chemical reaction" model. Nearly quantitative agreement of the enthalpies was achieved for the systems studied, except the amines in water. The latter required an empirical hydrophobic hydration term to be considered. The hydrogen bonds formation and breaking which accompany the mixtures formation leads to considerable excess volumes, while the size of the solute molecules is manifested rather in the compressibility of aqueous solutions. SANS evidenced that aqueous solutions are microheterogeneous on the nanometer-order length scale. The propensity to promote phase separation increases in the order: N-methylpiperidine < N-methylpyrrolidine < piperidine < pyrrolidine.

Hydration properties of glycylglycine in aqueous ionic liquid solutions at different temperatures: Volumetric and acoustic approach

The apparent molar volume and isentropic compression of glycylglycine in aqueous 1-methylimidazolium chloride, [mim][Cl], 1-ethyl-3-methylimidazolium chloride [C2mim][Cl], and 1-methyl-3-octylimidazolium chloride [C8mim][Cl] solutions have been calculated from the measured experimental data on density and speed of sound at temperature, T=288.15, 298.15 and 308.15K. The apparent molar volumes at infinite dilution, Vϕ0 and the apparent isentropic molar compression at infinite dilution Kϕ,S0, were also calculated. Furthermore, apparent specific volumes, apparent molar expansivity, Eϕ0, Hepler's constant values, ∂Eϕ0∂TP and hydration numbers, nH, have been evaluated to support the conclusions obtained from the volumetric and acoustic studies. The Hepler's constant values were found negative which indicating the peptide under study is predominantly a structure breaker due to hydrophobic hydration of small peptide in aqueous ionic liquid.

Dense Semi-Clathrates at High Pressure: A Study of the Water-tert-Butylamine System.

In situ high-pressure crystallization and diffraction techniques have been applied to obtain two very structurally distinct semi-clathrates of the tert-butylamine-water system with hydration numbers 5.65 and 5.8, respectively, thereby considerably reducing a notable hydration gap between the monohydrate and the 71/4 -hydrate that results when crystallization space is explored by temperature alone. Both structures can be considered as an intriguing solid-state example of hydrophobic hydration, in which the water network creates wide tert-butylamine-filled channels stabilized by cross-linking hydrogen bonds. The existence of interconnected channels might also add low hydration structures to a list of potential targets for hydrogen storage. A detailed analysis of the topology of host water and host-guest interactions is reported and extended to those of other hydrates of the compound. This analysis offers new insight into properties of the tert-butylamine-water system and provides some clues as to the occurrence of the sizable number of hydrates of this compound.

Solubility and preferential solvation of some n-alkyl-parabens in methanol + water mixtures at 298.15 K

Methyl, ethyl and propyl parabens equilibrium solubility was determined in (methanol+water) binary mixtures at 298.15K. The mole fraction solubility of these compounds increased in 503 (from 2.40×10−4 to 0.121), 1377 (from 9.86×10−5 to 0.136) and 4597 (from 3.73×10−5 to 0.171) times when passing from neat water to neat methanol, for methyl, ethyl and propyl parabens, respectively. All these solubility values were correlated with the Jouyban-Acree model. Preferential solvation parameters by methanol (δx1,3) of these parabens were derived from their thermodynamic solution properties using the inverse Kirkwood-Buff integrals (IKBI) method. For all compounds δx1,3 values are negative in water-rich mixtures but positive in mixtures with methanol mole fraction greater than 0.32. It is conjecturable that in the former case the hydrophobic hydration around non-polar groups of parabens plays a relevant role in the solvation. Besides, the preferential solvation of these solutes by methanol in mixtures of similar co-solvent compositions and in methanol-rich mixtures could be explained in terms of the higher basic behaviour of methanol.

Hydrophobic hydration and anomalous diffusion of elastin in an ethanolic solution.

Elastin is an important structural protein that confers elasticity to tissues. It is widely used in the biosynthesis of human elastic tissues and exhibits interesting properties. This study reports an insight into the unusual dispersion and anomalous diffusion of elastin in an ethanolic solution. Due to its complex hydrophobic structure, its dispersibility was found to be sensitive towards the hydrophobicity of the solvent. Electrophoresis measurements (zeta-potential data) revealed that its net polarity changed from an anionic to a cationic state with the decreasing solvent hydrophobicity (ethanol content in the solvent). An interesting transition temperature of ∼297 K was observed above which the hydrophobic interactions among the protein molecules became dominant. Double-layer repulsion between protein molecules competes with attractive hydrophobic interactions and causes molecular self-organization. A DLVO-based theoretical model showed that hydrophobic interactions were facilitated by a binary solvent (ethanol-water), and the repulsive double layer screening provided sufficient energy to overcome the interactions between hydrophobic domains in the protein molecule and allow the self-assembly to occur.

Aqueous self-assembly of hydrophobic macromolecules with adjustable rigidity of the backbone.

P(FpC3P) (Fp: CpFe(CO)2; C3P: propyl diphenyl phosphine) has a helical backbone, resulting from piano stool metal coordination geometry, which is rigid with intramolecular aromatic interaction of the phenyl groups. The macromolecule is hydrophobic, but the polarized CO groups can interact with water for aqueous self-assembly. The stiffness of P(FpC3P), which is adjustable by temperature, is an important factor influencing the morphologies of kinetically trapped assemblies. P(FpC3P)7 self-assembles in DMSO/water (10/90 by volume) into lamellae at 25 °C, vesicles at 40 °C and irregular aggregates at higher temperatures (60 and 70 °C). The colloidal stability decreases in the order of lamellae, vesicles and irregular aggregates. Dissipative particle dynamics (DPD) simulation reveals the same temperature-dependent self-assembled morphologies with an interior of hydrophobic aromatic groups covered with the metal coordination units. The rigid backbone at 25 °C accounts for the formation of the layered morphology, while the reduced rigidity of the same P(FpC3P)7 at 40 °C curves up the lamellae into vesicles. At a higher temperature (60 or 70 °C), P(FpC3P)7 behaves as a random coil without obvious amphiphilic segregation, resulting in irregular aggregates. The stiffness is, therefore, a crucial factor for the aqueous assembly of macromolecules without obvious amphiphilic segregation, which is reminiscent of the solution behavior observed for many hydrophobic biological macromolecules such as proteins.

The physicochemical properties and viscosity behavior of crown ether 18C6 in the mixture of water with N,N-dimethylformamide

Abstract The viscosity of 18-crown-6 (18C6) in the mixtures of N,N-dimethylformamide (DMF) and water (W) is measured within the temperature range of (293.15 to 308.15) K. The values of both dynamic, η, and relative viscosity, ηr, is calculated on the basis of the fluid flow time. The analysis of the viscosity coefficient B of Jones-Dole's equation as well as its derivative relative to temperature (dB/dT) is made. These functions play an important role in showing and discussing the interactions between the mixture component molecules. Moreover, it makes possible to determine their destroying or reinforcing influence on the solvent structure. The effective volume of (18C6 + nH2O) unit is calculated using Breslau-Miller equation and the hydration number of 18C6 supports the existence of hydrophobic hydration of those compounds. The results obtained are discussed in comparison to the results presented in our previous papers. The analysis performed demonstrates the fundamental difference in interactions between the water molecules and hydrophilic urea molecules as well as water molecules and hydrophobic 18C6 molecules. The effect of ring size of cyclic ethers such interactions was also shown.

Molecular dynamics study of micelles properties according to their size

Surfactants are molecules able to spontaneously self-assemble to form aggregates with well-defined properties, such as spherical micelles, planar bilayers, cylindrical micelles or vesicles. Micelles have notably several applications in many domains, such as drug delivery or membrane protein solubilization. In this context, the study of micelle formation in relation with the structural and physico-chemical properties of surfactants is of great interest to better control their use in the different application fields.In this work, we use the MD approach developed by Yoshii et al. and extend it to surfactants with different structures. We aim to systematically investigate different micellar properties as a function of the aggregates size by a molecular dynamics approach, to get an insight into the micellar organization and to collect some relevant descriptors about micelle formation. For this, we perform short MD simulations of preformed micelles of various sizes and analyze three parameters for each micelle size, namely the eccentricity of the micelles, the hydrophobic/hydrophilic surface ratio and the hydrophobic tails hydration. If these parameters are known descriptors of micelles, they were not yet studied in this way by MD.We show that eccentricity, used as “validator” parameter, exhibits minimal values when the aggregate size is close to the experimental aggregation number for surfactants that are known to form spherical micelles. This hence indicates that our methodology gives consistent results. The evolution of the two descriptors follows another scheme, with a sharp increase and decrease, respectively, followed by a leveling-off. The aggregate sizes at which this stabilization starts to occur are close to the respective aggregation number of each surfactant. In our approach, we validate the use of these descriptors to follow micelle formation by MD, from “simple” surfactants to more complex structures, like lipopeptides. Our calculations also suggest that some peculiar behavior, like that of TPC, can be highlighted by our approach.In the context of peptidic surfactants, our methodology could further help to improve computer simulations combined to molecular thermodynamic models to predict micellar properties of those more complex amphiphilic molecules.

Structural and Dynamic Insights of the Interaction between Tritrpticin and Micelles: An NMR Study

A large number of antimicrobial peptides (AMPs) acts with high selectivity and specificity through interactions with membrane lipid components. These peptides undergo complex conformational changes in solution; upon binding to an interface, one major conformation is stabilized. Here we describe a study of the interaction between tritrpticin (TRP3), a cathelicidin AMP, and micelles of different chemical composition. The peptide’s structure and dynamics were examined using one-dimensional and two-dimensional NMR. Our data showed that the interaction occurred by conformational selection and the peptide acquired similar structures in all systems studied, despite differences in detergent headgroup charge or dipole orientation. Fluorescence and paramagnetic relaxation enhancement experiments showed that the peptide is located in the interface region and is slightly more deeply inserted in 1-myristoyl-2-hydroxy-sn-glycero-3-phospho-1′-rac-glycerol (LMPG, anionic) than in 1-lauroyl-2-hydroxy-sn-glycero-3-phosphocholine (LLPC, zwitterionic) micelles. Moreover, the tilt angle of an assumed helical portion of the peptide is similar in both systems. In previous work we proposed that TRP3 acts by a toroidal pore mechanism. In view of the high hydrophobic core exposure, hydration, and curvature presented by micelles, the conformation of TRP3 in these systems could be related to the peptide’s conformation in the toroidal pore.

Zeta potential of PNIPAM microgel particles dispersed in water—effects of charged radical initiators vs. OH− ion adsorption

It has been known that zeta potential (ζ) or electrophoretic mobility of poly(N-isopropyl acrylamide) (PNIPAM) gel particles in water significantly increase in the magnitude with increasing the temperature. This phenomenon has been interpreted as caused by an enhancement of the surface charge density, which was derived from charged initiator used for the gel preparation, due to the temperature-induced gel deswelling. On the other hand, it has also been established that oil droplets dispersed in water show a negative ζ, which has been ascribed to a specific adsorption of OH− ions from aqueous phase to the hydrophobic hydration layer around the nonpolar droplets. In the present study, we attempted to see if the OH− adsorption actually contributes toζ of PNIPAM microgel particles prepared with four kinds of radical initiators including neutral one. ζ measurements were carried out to find that not only the neutral gel particles but also weakly cationic ones showed a significantly negativeζ at the higher temperature region where the gel collapse occurred. ζ values in the presence of 10−4 M NaCl, NaOH, or HCl were also measured and proved to be consistent with the OH− ion adsorption mechanism.

Further Numerical Analyses on the Solubility of Sulfapyridine in Ethanol + Water Mixtures

Background: Dissolution thermodynamic quantities of sulfapyridine (SP) have been reported in the literature for aqueous alcoholic mixtures. Nevertheless, no attempts to evaluate the preferential solvation of this drug in this binary system, have been reported. In this way, the inverse Kirkwood-Buff integrals (IKBI) were used to evaluate this behavior in solution. Methods: Solubility data for SP dissolved in binary ethanol (EtOH) + water mixtures at various temperatures were mathematically represented using the Jouyban-Acree (J-A) model. The preferential solvation parameters of SP by EtOH (δx1,3) in EtOH + water mixtures were obtained from some thermodynamic properties of the mixtures by means of the IKBI method. Results: Solubility of SP in EtOH + water mixtures is adequately described by the J-A model in second order. Moreover, SP is sensitive to specific solvation effects, so the δx1,3 values are negative in water-rich and EtOH-rich mixtures indicating preferential solvation by water in these mixtures. By contrary, δx1,3 values are positive in the range 0.24 < x1 < 0.53 indicating preferential solvation by EtOH in these mixtures. Conclusion: It can be assumed that in water-rich mixtures the hydrophobic hydration around the aromatic rings plays a relevant role in the solvation. The higher drug solvation by EtOH in mixtures of similar solvent proportions could be due to polarity effects. Moreover, in EtOH + water mixtures SP could be acting as a Lewis acid with the EtOH molecules and in EtOH-rich mixtures the drug could be acting as a Lewis base with water molecules.

Solubility and Preferential Solvation of the Flavonoid Naringenin in Some Aqueous/Organic Solvent Mixtures

The solubility of the antioxidant flavonoid naringenin as well as its preferential solvation was studied in different aqueous solutions containing 0–100 % (v/v) of acetonitrile (ACN) and 1,4-dioxane (DOX) at temperature 25.0 ± 0.1 °C. From the solubility data, both the Gibbs energy changes involved with the solublization process, $$ \Delta G_{\text{s}}^{\text{o}} $$ , and the preferential solvation parameters of the solute naringenin by these co-solvents, δx cosolv,S, were determined. The results show that the equilibrium solubility increases with increasing co-solvent concentration. Moreover, it became clear that the preferential solvation of naringenin is sensitive to changes in solvent composition, so the preferential solvation parameters δx ACN,S and δx DOX,S are negative in water-rich mixtures but positive in compositions from 50 % (v/v) ACN (x ACN = 0.25) and DOX (x DOX = 0.17) up to the pure co-solvents. Possibly, in water-rich mixtures the structuring of water molecules around the non-polar groups by hydrophobic hydration contributes to lowering of the net δx cosolv,S to negative values. The preferential solvation by the co-solvent in the range 50–100 % (v/v) could be related to the greater basicity of the co-solvents and its interactions with hydroxyl groups of the flavonoid.

Solubility and preferential solvation of phenacetin in methanol + water mixtures at 298.15 K

ABSTRACTThe mole fraction solubility of phenacetin (PNC) in methanol + water binary solvent mixtures at 298.15 K was determined along with density of the saturated solutions. All these solubility values were correlated with the Jouyban–Acree model. Preferential solvation parameters of PNC by methanol (δx1,3) were derived from their thermodynamic solution properties using the inverse Kirkwood–Buff integrals (IKBI) method. δx1,3 values are negative in water-rich mixtures but positive in methanol mole fraction of >0.32. It is conjecturable that in the former case the hydrophobic hydration around non-polar groups of PNC plays a relevant role in the solvation. The higher solvation by methanol in mixtures of similar cosolvent compositions and methanol-rich mixtures could be explained in terms of the higher basic behaviour of methanol.

Studies of relationship between polymer structure and hydration environment in amphiphilic polytartaramides

ABSTRACTThe relationships between the chemical structures and hydration environment of the polymers can provide significant insight into the water‐amphiphilic polymer interactions. Here, the hydrophobicity of amphiphilic block copolymers poly(ethylene tartaramide‐b‐alkyl isocyanate) is gradually tuned by using of a series of pendant alkyl (isopropyl, n‐butyl, cyclopentyl, and cyclohexyl) groups. Dynamics of hydration probed by low‐field NMR relaxometry exhibits a heterogeneous environment of water molecules, corresponding to tightly bound water with slow re‐orientational mobility and loosely bound water with fast re‐orientational mobility. Progressively larger amounts of bound water are present in the copolymers, ongoing from pendant isopropyl, n‐butyl, cyclopentyl, and finally to cyclohexyl group. Water in the copolymer bearing the cyclohexyl group has a significantly high partial specific heat capacity. Therefore, hydrophobic interaction between the polymer and water is enhanced when the hydrophobicity of the polymer is increased, resulting in considerable hydrophobic hydration with decreased mobility of the bound water. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2017, 55, 138–145

Solubility and Preferential Solvation of Sulfanilamide, Sulfamethizole and Sulfapyridine in Methanol + Water Mixtures at 298.15 K

The equilibrium solubilities of sulfanilamide, sulfamethizole and sulfapyridine in methanol + water mixtures at 298.15 K were determined and the preferential solvation parameters were derived from their thermodynamic solution properties by means of the inverse Kirkwood–Buff integrals. In all cases the drug solubility was the lowest in neat water and highest in neat methanol. The preferential solvation parameters for methanol (δx 1,3) are negative in water-rich mixtures but positive in compositions from 0.32 in mole fraction of methanol to pure methanol. Based on these results it is conjecturable that in the former case hydrophobic hydration around the aromatic rings plays the main role in the drug’s solvation. The higher solvation by methanol in mixtures of similar cosolvent compositions and in methanol-rich mixtures can be explained in terms of the higher basic behavior of this co-solvent interacting with the Lewis acidic groups of the drugs. Besides, the drugs’ solubilities were mathematically represented by using the Jouyban–Acree model obtaining average percentage deviations lower than 2.6 % for correlative studies.