Small Hydrophobic Solutes Research Articles

The role of the water contact layer on hydration and transport at solid/liquid interfaces

Understanding the structure in the nanoscopic region of water that is in direct contact with solid surfaces, so-called contact layer, is key to quantifying macroscopic properties that are of interest to e.g. catalysis, ice nucleation, nanofluidics, gas adsorption, and sensing. We explore the structure of the water contact layer on various technologically relevant solid surfaces, namely graphene, MoS[Formula: see text], Au(111), Au(100), Pt(111), and Pt(100), which have been previously hampered by time and length scale limitations of ab initio approaches or force field inaccuracies, by means of molecular dynamics simulations based on ab initio machine learning potentials built using an active learning scheme. Our results reveal that the in-plane intermolecular correlations of the water contact layer vary greatly among different systems: Whereas the contact layer on graphene and on Au(111) is predominantly homogeneous and isotropic, it is inhomogeneous and anisotropic on MoS[Formula: see text], on Au(100), and on the Pt surfaces, where it additionally forms two distinct sublayers. We apply hydrodynamics and the theory of the hydrophobic effect, to relate the energy corrugation and the characteristic length-scales of the contact layer with wetting, slippage, the hydration of small hydrophobic solutes and diffusio-osmotic transport. Thus, this work provides a microscopic picture of the water contact layer and links it to macroscopic properties of liquid/solid interfaces that are measured experimentally and that are relevant to wetting, hydrophobic solvation, nanofluidics, and osmotic transport.

S.O.S: Shape, orientation, and size tune solvation in electrocatalysis.

Current models to understand the reactivity of metal/aqueous interfaces in electrochemistry, e.g., volcano plots, are based on the adsorption free energies of reactants and products, which are often small hydrophobic molecules (such as in CO2 and N2 reduction). Calculations played a major role in the quantification and comprehension of these free energies in terms of the interactions that the reactive species form with the surface. However, solvation free energies also come into play in two ways: (i) by modulating the adsorption free energy together with solute-surface interactions, as the solute has to penetrate the water adlayer in contact with the surface and get partially desolvated (which costs free energy); (ii) by regulating transport across the interface, i.e., the free energy profile from the bulk to the interface, which is strongly non-monotonic due to the unique nature of metal/aqueous interfaces. Here, we use constant potential molecular dynamics to study the solvation contributions, and we uncover huge effects of the shape and orientation (on top of the already known size effect) of small hydrophobic and amphiphilic solutes on their adsorption free energy. We propose a minimal theoretical model, the S.O.S. model, that accounts for size, orientation, and shape effects. These novel aspects are rationalized by recasting the concepts at the base of the Lum-Chandler-Weeks theory of hydrophobic solvation (for small solutes in the so-called volume-dominated regime) into a layer-by-layer form, where the properties of each interfacial region close to the metal are explicitly taken into account.

A Heteronuclear NMR Study of Aqueous Lithium Salt Solutions of l-Alanine: Revealing Solute Hydrophobic Association through the NMR B' Coefficient.

In the present study, a set of heteronuclear NMR approaches has been adopted to investigate the solution behavior of a small hydrophobic solute l-alanine in the presence of lithium (Li) salts. The presence of salts plays a major role in determining the structure and solvation of biomolecules. It therefore evokes interest to understand the effect of Li salts on amino acids (alanine), the building block of biomolecules. The ionic solute dynamics in the present case has been probed using 1H, 7Li, and 13C nuclei available in the aqueous Li salt solution of l-alanine. Nuclear longitudinal spin relaxation of alanine protons was examined at a variable concentration range of three lithium salts, i.e., LiCl, Li2SO4 and LiClO4, to introduce the NMR B' coefficient for each salt defining ionic solute/solvent interaction in the solution. Analysis of the active relaxation mechanism of 7Li spin-lattice relaxation further revealed the presence of alanine in the solvation shell of Li ion depending on the anionic counterpart.

Size-Dependent Order-Disorder Crossover in Hydrophobic Hydration: Comparison between Spherical Solutes and Linear Alcohols.

Theory and computer simulation studies have predicted that water molecules around hydrophobic molecules should undergo an order–disorder transition with increasing solute size around a 1 nm length scale. Some theories predict the formation of a clathrate-like ordered structure around smaller hydrophobic solutes (<1 nm) and the formation of disordered vapor–liquid interfaces around larger solutes (>1 nm) and surfaces. Experimental validation of these predictions has often been elusive and contradictory. High-resolution Raman spectroscopy has detected that water around small hydrophobic solutes shows a signature similar to that of bulk water at lower temperature (increased ordering and a stronger hydrogen-bonded network). Similarly, water around larger solutes shows an increasing population of dangling OH bonds very similar to higher temperature bulk water. Thus, the solute size dependence of the structure and dynamics of water around hydrophobic molecules seems to have an analogy with the temperature dependence in bulk water. In this work, using atomistic classical molecular dynamics (MD) simulations, we have systematically investigated this aspect and characterized this interesting analogy. Structural order parameters including the tetrahedral order parameter (Q), hydrogen bond distribution, and vibrational power spectrum highlight this similarity. However, in contrast to the experimental observations, we do not observe any length-dependent crossover for linear hydrophobic alcohols (n-alkanols) using classical MD simulations. This is in agreement with earlier findings that linear alkane chains do not demonstrate the length-dependent order–disorder transition due to the presence of a sub-nanometer length scale along the cross section of the chain. Moreover, the collapsed state of linear hydrocarbon chains is not significantly populated for smaller chains (number of carbons below 20). In the context of our computational results, we raise several pertinent questions related to the sensitivity of various structural and dynamical parameters toward capturing these complex phenomena of hydrophobic hydration.

Temperature Dependence of Hydrophobic and Hydrophilic Forces and Interactions.

Molecular dynamics simulations are used to compare the forces and Gibbs free energies associated with bringing small hydrophobic and hydrophilic solutes together in an aqueous solution at different temperatures between 280 and 360 °K. For the hydrophilic solutes, different relative orientations are used to distinguish between direct, intersolute hydrogen bonds (Hbond) and solutes simultaneously hydrogen bonding to a solvent water bridge. Interestingly, the temperature dependence of the hydrophobic and directly hydrogen bonding solutes turns out to be opposite to that of the bridged hydrophilic solutes, with the ΔG becoming more negative for the former and less negative for the latter with increasing temperature. Dissection of the free energy curves into enthalpy and entropy contributions, and further separation of the enthalpy term into solute-solute, solute-solvent, and solvent-solvent components provides insight into the physical molecular causes for the distinctive thermodynamic results. Finally, it is reasoned how the opposite temperature dependencies of the two types of hydrophilic interactions provide a rationale for the cold denaturation of proteins.

Size dependence of hydrophobic hydration at electrified gold/water interfaces

Hydrophobic hydration at metal/water interfaces actively contributes to the energetics of electrochemical reactions, e.g. [Formula: see text] and [Formula: see text] reduction, where small hydrophobic molecules are involved. In this work, constant applied potential molecular dynamics is employed to study hydrophobic hydration at a gold/water interface. We propose an adaptation of the Lum-Chandler-Weeks (LCW) theory to describe the free energy of hydrophobic hydration at the interface as a function of solute size and applied voltage. Based on this model we are able to predict the free energy cost of cavity formation at the interface directly from the free energy cost in the bulk plus an interface-dependent correction term. The interfacial water network contributes significantly to the free energy, yielding a preference for outer-sphere adsorption at the gold surface for ideal hydrophobes. We predict an accumulation of small hydrophobic solutes of sizes comparable to CO or [Formula: see text], while the free energy cost to hydrate larger hydrophobes, above 2.5-Å radius, is shown to be greater at the interface than in the bulk. Interestingly, the transition from the volume dominated to the surface dominated regimes predicted by the LCW theory in the bulk is also found to take place for hydrophobes at the Au/water interface but occurs at smaller cavity radii. By applying the adapted LCW theory to a simple model addition reaction, we illustrate some implications of our findings for electrochemical reactions.

Characterizing Polymer Hydration Shell Compressibilities with the Small-System Method.

The small-system method (SSM) exploits the unique feature of finite-sized open systems, whose thermodynamic quantities scale with the inverse system size. This scaling enables the calculation of properties in the thermodynamic limit of macroscopic systems based on computer simulations of finite-sized systems. We herein extend the SSM to characterize the hydration shell compressibility of a generic hydrophobic polymer in water. By systematically increasing the strength of polymer-water repulsion, we find that the excess inverse thermodynamic correction factor () and compressibility () of the first hydration shell change sign from negative to positive. This occurs with a concurrent decrease in water hydrogen bonding and local tetrahedral order of the hydration shell water. The crossover lengthscale corresponds to an effective polymer bead diameter of 0.7 nm and is consistent with previous works on hydration of small and large hydrophobic solutes. The crossover lengthscale in polymer hydration shell compressibility, herein identified with the SSM approach, relates to hydrophobic interactions and macromolecular conformational equilibria in aqueous solution. The SSM approach may further be applied to study thermodynamic properties of polymer solvation shells in mixed solvents.

Salt Effects on Hydrophobic Solvation: Is the Observed Salt Specificity the Result of Excluded Volume Effects or Water Mediated Ion-Hydrophobe Association?

The solubility of hydrophobic molecules in water is sensitive to salt addition in an ion-specific manner. Such "salting-out" and "salting-in" properties have been shown to be a major contributor to the measured ion-specific Hofmeister effects that are observed in many biophysical phenomena. Various theoretical models have suggested a number of disparate mechanisms for salting-out (salting-in) of hydrophobic moieties, the most popular of which include preferential interaction, water-mediated association, and electrostriction models. However, a complete molecular level description of this ion-specificity is not yet available. This work investigates the ion-specific nature of hydrophobic solvation by studying how sodium and chloride salts affect the thermodynamics of 1,2-hexanediol micellization. The results of this study are analyzed in terms of scaled-particle theory and we show that salt addition can affect hydrophobic solvation in two modalities: salt addition changes the cavitation free energy; salt addition also influences the solvent-solute interaction energy by changing the hydration of the hydrophobic solute. These two effects are salt specific in nature and we suggest that for small hydrophobic solutes these effects are the main cause of salt-specific Hofmeister effects on their solubility.

Why do water molecules around small hydrophobic solutes form stronger hydrogen bonds than in the bulk?

Molecular solutes are known to have a strong effect on the structural and dynamical properties of the surrounding water. In our recent study (PNAS, 114, 322 (2017)) we have identified the presence of strengthened water hydrogen bonds near hydrophobic solutes by using both IR spectroscopy and ab-initio molecular dynamics simulations. The water molecules involved in the enhanced hydrogen bonding have been shown to display extensive structural ordering and restricted mobility. We observed that an individual pair of water molecules can make stronger hydrogen bond to each other if it is not surrounded by intercalating water molecules. Here we present compelling simulation results which unravel a simple mechanistic picture of the emergence of the hydrogen bond (HB) strengthening around solvated methane. We show explicitly that actual absence of water molecules within the excluded volume due to the hydrophobic molecule assures smaller residual torque on neighboring water molecules enabling the formation of stronger HBs between them.

Importance of Solvents' Translational-Rotational Coupling for Translational Jump of a Small Hydrophobic Solute in Supercooled Water.

Despite clear evidence of sudden translational jump occurrence of a solute in supercooled water, a detailed mechanism of this jump is still lacking. A previous work [ Indra , S. ; Daschakraborty , S. Chem. Phys. Lett. 2017 , 685 , 322 - 327 ] put forward a mechanism of this jump from an initial solvent cage to a final one. The proposed mechanism is astoundingly similar to that of the electron/proton transfer reaction in aqueous solution. The above study identified the spatial prearrangement (rearrangement before the jump occurrence) of cage forming water solvent molecules as the actual reaction coordinate. However, the study completely ignored the contribution of the orientational prearrangement of solvent water molecules. In this study, we have monitored both the spatial and the orientational prearrangements of water solvent molecules at subzero temperatures during the jump occurrence of the solute. We have found overwhelming contributions of both the spatial and orientational prearrangements of water, which symmetrize the hydration structure at the initial and final cage positions to facilitate the jump event. Through a systematic temperature dependence study (from T = 240 to 270 K), we have found clear evidence that a strong synchronization between translational and rotational prearrangements of the solvent water molecules is crucial for the solute's jump from one solvent cage to another in supercooled water (below T = 252 K). The above translation-rotation synchronization is probably due to the cooperative movement of solvent water molecules forming clusters in the supercooled region. Since these cooperative dynamics are the consequence of the spatiotemporal heterogeneity in the medium, we infer that the large-amplitude translational jump of the nonpolar solute probably stems from the spatiotemporal heterogeneity of supercooled water. At temperatures above the melting point, this cooperativity is partly lost since the translational and orientational prearrangements become somewhat independent of each other.

Replica Ornstein-Zernike Theory Applied for Studying the Equilibrium Distribution of Electrolytes across Model Membranes.

By means of replica Ornstein-Zernike theory (supplemented in a few cases by Monte Carlo simulations) we examined the distribution of an annealed primitive model +1:-1 electrolyte in a mixture with uncharged hard spheres, or another model +1:-1 or +2:-1 electrolyte inside and outside the quenched vesicles, decorated by a model membrane, and across the membrane phase. We explored the influence of the size and charge of the annealed fluid on the partition equilibrium, as well as the effect of the vesicle size and membrane interaction parameters (repulsive barrier height, attractive depth, and membrane width). A hydrophobic cation, present in the mixture with NaCl, slightly enhanced the concentration of sodium ions inside the model vesicle, compared to pure NaCl solution. The replica theory was in good agreement with computer simulations and as such adequate for studying partitioning of small and hydrophobic ions or hydrophobic solutes across model membranes.

Molecular dynamics study of the structure of anionic SDS, cationic DTAC, zwitterionic DDAO, and nonionic C12E8 spherical micelles in solution

Molecular dynamics calculations for anionic SDS, cationic DTAC, zwitterionic DDAO, nonionic C12E8 micelles, and dodecane droplets as a reference, were carried out in order to obtain the relation between the head group charges and structure of the micelle. The radial density profile of the carbon atom of hydrophobic tail shows a low-density region at the micelle center, where small hydrophobic solutes may be solubilized. This is commonly found among the micelles investigated in the present study. This indicates that the deep part of the micelle core is not influenced by the head group charges. In contrast, structure of surface of the hydrophobic core of the micelles is strongly influenced by the head groups. Fluctuation of the surface of the ionic SDS micelle is restricted by the strong Coulombic interaction between the charges of the sulfate groups and counter sodium ions. In the other micelles, this effect disappears so that a large fluctuation occurs on the micelle surface. The volume of solvent water decreases when the ionic SDS and DTAC micelles dissolved into water. Because of the strong electrostatic field around the micelle, orientation of water molecules has strong correlations with the micelles. Then, the tetrahedral water structure breaks. In particular, the density increases around the SDS micelles because of the strong attraction toward the sulfate groups. Thus, the volume shrinkage occurs.

Regenerated Cellulose Capsules for Controlled Drug Delivery, Part 2: Modulating Membrane Permeability by Incorporation of Depolymerized Cellulose and Altering Membrane Thickness

For application of regenerated cellulose (RC) membranes in capsule dosage forms, the methods to modify drug release from these membranes are described. Membranes were fabricated by blending native and depolymerized celluloses dissolved in dimethyl sulfoxide and paraformaldehyde solvent system, prior to casting on molds, precipitation in water, and thermal annealing. The effect of laminating layers of RC to fabricate membranes with increasing thickness was also investigated. Solute diffusion studies using ionic and hydrophobic solutes, as well as large protein molecules, were conducted in side-by-side diffusion cells. Microscopic as well as physiological evaluation of these membranes indicated that pore size, porosity, and water uptake decreased as the fraction of depolymerized cellulose increased in the membranes. Permeability analysis of small ionic and hydrophobic solutes indicated that the solute transport across the hydrated membrane occurs through diffusion in the water-filled pores that are formed in situ. The apparent path for solute diffusion increases as the fraction of depolymerized cellulose increases. Permeability analysis of large protein molecules indicated that the pore sizes and distribution in these membranes is heterogeneous. Increasing the membrane thickness by lamination of RC does not influence porosity but causes formation of dead-end pores because of blocking by subsequent laminate layers.

Thermodynamic and Structural Evidence for Reduced Hydrogen Bonding among Water Molecules near Small Hydrophobic Solutes.

The structure of water molecules near a hydrophobic solute remains elusive despite a long history of scrutiny. Here, we re-examine the subtle issue by a combination of thermodynamic analysis for Henry's constants of several nonpolar gases over a broad range of temperatures and molecular dynamic simulations for the water structure in the hydration shell using several popular semiempirical models of liquid water. Both the structural and thermodynamic data indicate that hydrophobic hydration reduces the degree of the hydrogen bonding among water molecules, and the effect becomes more prominent at high temperatures. Hydrogen-bond formation is slightly hindered near a hydrophobic solute due to the restriction of the degree of freedom for water molecules in the solvation shell, and the confinement effect becomes more significant as temperature increases. Reduction in the extent of hydrogen bonding is fully consistent with a positive contribution of a small hydrophobic solute to the solution heat capacity. As predicted by the scaled-particle theory, both Henry's constants and simulation results suggest that the hydration entropy is determined primarily by cavity formation in liquid water, with its magnitude rising with the solute size but declining with temperature.

Water around fullerene shape amphiphiles: A molecular dynamics simulation study of hydrophobic hydration.

Fullerene C60 sub-colloidal particle with diameter ∼1 nm represents a boundary case between small and large hydrophobic solutes on the length scale of hydrophobic hydration. In the present paper, a molecular dynamics simulation is performed to investigate this complex phenomenon for bare C60 fullerene and its amphiphilic/charged derivatives, so called shape amphiphiles. Since most of the unique properties of water originate from the pattern of hydrogen bond network and its dynamics, spatial, and orientational aspects of water in solvation shells around the solute surface having hydrophilic and hydrophobic regions are analyzed. Dynamical properties such as translational-rotational mobility, reorientational correlation and occupation time correlation functions of water molecules, and diffusion coefficients are also calculated. Slower dynamics of solvent molecules—water retardation—in the vicinity of the solutes is observed. Both the topological properties of hydrogen bond pattern and the "dangling" -OH groups that represent surface defects in water network are monitored. The fraction of such defect structures is increased near the hydrophobic cap of fullerenes. Some "dry" regions of C60 are observed which can be considered as signatures of surface dewetting. In an effort to provide molecular level insight into the thermodynamics of hydration, the free energy of solvation is determined for a family of fullerene particles using thermodynamic integration technique.

Water structuring over the hydrophobic surface of cellulose.

Many important biological solutes possess not only polar and hydrogen-bonding functionalities but also weakly hydrating, or hydrophobic, surfaces. While the aggregation of these hydrophobic surfaces has been shown to play an important role in the aggregation of individual chains of cellulose, it is not known whether the water structuring imposed by these hydrophobic surfaces more closely resembles that associated with small hydrophobic solutes like methane and fats or more closely resembles that associated with extended hydrophobic surfaces like mica or waxy planes. By using molecular dynamics simulations to characterize the water molecule orientations over different regions of the 100 surface of cellulose in contact with water, it was found that the hydrophobic strips of the cellulose crystal are sufficiently narrow that they hydrate like a fatty acid chain, rather than like a more extended surface, suggesting that their aggregation would be dominated by entropy rather than enthalpy.

Single water entropy: hydrophobic crossover and application to drug binding.

Entropy of water plays an important role in both chemical and biological processes e.g. hydrophobic effect, molecular recognition etc. Here we use a new approach to calculate translational and rotational entropy of the individual water molecules around different hydrophobic and charged solutes. We show that for small hydrophobic solutes, the translational and rotational entropies of each water molecule increase as a function of its distance from the solute reaching finally to a constant bulk value. As the size of the solute increases (0.746 nm), the behavior of the translational entropy is opposite; water molecules closest to the solute have higher entropy that reduces with distance from the solute. This indicates that there is a crossover in translational entropy of water molecules around hydrophobic solutes from negative to positive values as the size of the solute is increased. Rotational entropy of water molecules around hydrophobic solutes for all sizes increases with distance from the solute, indicating the absence of crossover in rotational entropy. This makes the crossover in total entropy (translation + rotation) of water molecule happen at much larger size (>1.5 nm) for hydrophobic solutes. Translational entropy of single water molecule scales logarithmically (Str(QH) = C + kB ln V), with the volume V obtained from the ellipsoid of inertia. We further discuss the origin of higher entropy of water around water and show the possibility of recovering the entropy loss of some hypothetical solutes. The results obtained are helpful to understand water entropy behavior around various hydrophobic and charged environments within biomolecules. Finally, we show how our approach can be used to calculate the entropy of the individual water molecules in a protein cavity that may be replaced during ligand binding.

A nucleation-based method to study hydrophobic interactions under confinement: enhanced hydrophobic association driven by energetic contributions.

A novel simulation approach was developed and applied to the study of hydrophobic interactions for a small hydrophobic solute pair under confinement. In this method, the aggregation-volume-bias Monte Carlo algorithm, developed originally for nucleation studies, is used to evaluate the association free energy with water molecules for a methane pair through the gradual addition of water molecules into a nanometer-sized sphere. Through a thermodynamic cycle, this method allows for a convenient examination of the free energy difference between two different solvated configurations without sampling any of the configurations in between. The potential of mean force (PMF) for a methane pair under confinement obtained from this method reveals that the stability of the contact pair configuration can be enhanced compared to that in bulk water, which is in agreement with previous studies. Also, constraining the center of this methane pair at the center of this confined volume yields a PMF with a metastable solvent separated configuration, resembling more closely the PMF from the bulk-phase system compared to previous studies in which this solvent-separated minimum was found to be completely absent. A combination with histogram reweighting enables the study of this association behavior at different thermodynamic conditions without additional simulations. From a comprehensive thermodynamic analysis, it is evident that such hydrophobic association, known to be entropically driven in the bulk-phase system at ambient conditions, is entropically favorable only when a suitable range of solvent molecules is added to the confined system. More importantly, the energetic contributions are a favorable factor that explains the enhanced hydrophobic association toward the high number of solvent molecules.

Characterization of the Methane-Graphene Hydrophobic Interaction in Aqueous Solution from Ab Initio Simulations.

In this article, the interaction between a methane molecule and a graphene plane in liquid water has been characterized employing DFT-based free energy Molecular Dynamics calculations. This system represents a good model to understand the generic interaction between a small hydrophobic solute (methane molecule) and an extense hydrophobic surface (graphene plane). The structural and dynamical properties of graphene and methane hydration water are analyzed and found to be closely related to the main features of the potential of mean force. The results could be used in coarse-grained models to take into account the effect of the hydrophobic interaction in realistic systems relevant to experiment.

On the Thermodynamics and Kinetics of Hydrophobic Interactions at Interfaces

We have studied how primitive hydrophobic interactions between two or more small nonpolar solutes are affected by the presence of surfaces. We show that the desolvation barriers present in the potential of mean force between the solutes in bulk water are significantly reduced near an extended hydrophobic surface. Correspondingly, the kinetics of hydrophobic contact formation and breakage are faster near a hydrophobic surface than near a hydrophilic surface or in the bulk. We propose that the reduction in the desolvation barrier is a consequence of the fact that water near extended hydrophobic surfaces is akin to that at a liquid-vapor interface and is easily displaced. We support this proposal with three independent observations. First, when small hydrophobic solutes are brought near a hydrophobic surface, they induce local dewetting, thereby facilitating the reduction of desolvation barriers. Second, our results and those of Patel et al. (Proc. Natl. Acad. Sci. U.S.A. 2011, 108, 17678-17683) show that, whereas the association of small solutes in bulk water is driven by entropy, that near hydrophobic surfaces is driven by enthalpy, suggesting that the physics of interface deformation is important. Third, moving water away from its vapor-liquid coexistence, by applying hydrostatic pressure, leads to recovery of bulklike signatures (e.g., the presence of a desolvation barrier and an entropic driving force) in the association of solutes. These observations for simple solutes also translate to end-to-end contact formation in a model peptide with hydrophobic end groups, for which lowering of the desolvation barrier and acceleration of contact formation are observed near a hydrophobic surface. Our results suggest that extended hydrophobic surfaces, such as air-water or hydrocarbon-water surfaces, could serve as excellent platforms for catalyzing hydrophobically driven assembly.