Water-mediated aggregation of 2-butoxyethanol.

Water plays an important role in mediating hydrophobic interactions, and yet open questions remain regarding the magnitude, and even the sign, of water-mediated contributions to the potential of mean force between a pair of oily molecules dissolved in water. Here, the water-mediated interaction between 2-butoxyethanol (BE) molecules dissolved in water is quantified using Raman multivariate curve resolution (Raman-MCR), molecular dynamics (MD) simulations, and random mixing (RM) predictions. Our results indicate that the number of contacts between BE molecules at concentrations between 0.2 M and 1 M exceeds RM predictions, but is less than some MD predictions. Moreover, the potential of mean force between BE molecules in water has a well depth that is shallower than the direct interaction between 1-ethoxybutane chains in the gas phase, and thus the water-mediated contribution to BE aggregation is repulsive, as it pulls BE molecules apart rather than pushing them together.

Finite lattice model for molecular aggregation equilibria. Boolean statistics, analytical approximations, and the macroscopic limit.

Molecular processes, ranging from hydrophobic aggregation and protein binding to mesoscopic self-assembly, are typically driven by a delicate balance of energetic and entropic non-covalent interactions. Here, we focus on a broad class of such processes in which multiple ligands bind to a central solute molecule as a result of solute-ligand (direct) and/or ligand-ligand (cooperative) interaction energies. Previously, we described a weighted random mixing (WRM) mean-field model for such processes and compared the resulting adsorption isotherms and aggregate size distributions with exact finite lattice (FL) predictions, for lattices with up to n = 20 binding sites. Here, we compare FL predictions obtained using both Bethe-Guggenheim (BG) and WRM approximations, and find that the latter two approximations are complementary, as they are each most accurate in different aggregation regimes. Moreover, we describe a computationally efficient method for exhaustively counting nearest neighbors in FL configurations, thus making it feasible to obtain FL predictions for systems with up n = 48 binding sites, whose properties approach the thermodynamic (infinite lattice) limit. We further illustrate the applicability of our results by comparing lattice model and molecular dynamics simulation predictions pertaining to the aggregation of methane around neopentane.

Contacts Between Alcohols in Water Are Random Rather than Hydrophobic.

Given the importance of water-mediated hydrophobic interactions in a wide range of biological and synthetic self-assembly processes, it is remarkable that both the sign and the magnitude of the hydrophobic interactions between simple amphiphiles, such as alcohols, remain unresolved. To address this question, we have performed Raman hydration-shell vibrational spectroscopy and polarization-resolved femtosecond infrared experiments, as well as random mixing and molecular dynamics simulations. Our results indicate that there are no more hydrophobic contacts in aqueous solutions of alcohols ranging from methanol to tertiary butyl alcohol than in random mixtures of the same concentration. This implies that the interaction between small hydrophobic groups is weaker than thermal energy fluctuations. Thus, the corresponding water-mediated hydrophobic interaction must be repulsive, with a magnitude sufficient to negate the attractive direct van der Waals interaction between the hydrophobic groups.

Micelle Structure and Hydrophobic Hydration.

Despite the ubiquity and utility of micelles self-assembled from aqueous surfactants, longstanding questions remain regarding their surface structure and interior hydration. Here we combine Raman spectroscopy with multivariate curve resolution (Raman-MCR) to probe the hydrophobic hydration of surfactants with various aliphatic chain lengths, and either anionic (carboxylate) or cationic (trimethylammonium) head groups, both below and above the critical micelle concentration. Our results reveal significant penetration of water into micelle interiors, well beyond the first few carbons adjacent to the headgroup. Moreover, the vibrational C-D frequency shifts of solubilized deuterated n-hexane confirm that it resides in a dry, oil-like environment (while the localization of solubilized benzene is sensitive to headgroup charge). Our findings imply that the hydrophobic core of a micelle is surrounded by a highly corrugated surface containing hydrated non-polar cavities whose depth increases with increasing surfactant chain length, thus bearing a greater resemblance to soluble proteins than previously recognized.

Influence of a Neighboring Charged Group on Hydrophobic Hydration Shell Structure.

Raman multivariate curve resolution (Raman-MCR), as well as quantum and classical calculations, are used to probe water structural changes in the hydration shells of carboxylic acids and tetraalkyl ammonium ions with various aliphatic chain lengths. The results reveal that water molecules in the hydration shell around the hydrophobic chains undergo a temperature and chain length dependent structural transformation resembling that previously observed in aqueous solutions of n-alcohols. Deprotonation of the carboxylic acid headgroup (at pH ∼ 7) is found to suppress the onset of the hydration-shell structural transformation around the nearest aliphatic methylene group. Tetraalkyl ammonium cations are found to more strongly suppress the water structural transformation, perhaps reflecting the greater intramolecular charge delocalization and suppression of dangling OH defects in water's tetrahedral H-bond network. The observed coupling between ionic and hydrophobic groups, as well as the associated charge asymmetry, may influence the hydrophobicity of proteins and other materials.

Charge asymmetry at aqueous hydrophobic interfaces and hydration shells.

Guilty as charged: Water is often modeled as a dielectric continuum, but the molecular structure of water is asymmetric. Two ions that have a virtually identical size, shape, and structure, but an opposite charge sign have been investigated to see whether charge makes a fundamental difference to water structuring. The spectroscopic data for the hydration and interface structures are found to be remarkably different for opposite charges.

Molecular aggregation equilibria. Comparison of finite lattice and weighted random mixing predictions.

Molecular aggregation equilibria are described using finite lattice and mean field theoretical modeling strategies, both built upon a random mixture reference system. The resulting predictions are compared with each other for systems in which each aggregate consists of a central solute molecule whose first coordination shell can accommodate multiple bound ligands. Solute-ligand (direct) and ligand-ligand (cooperative) interactions are found to influence aggregate size distributions in qualitatively different ways, as direct interactions produce a shape-invariant transformation of the aggregate size distribution, whereas cooperative interactions can lead to a vapor-liquid-like transformation. When half the ligand binding sites are filled, the corresponding aggregate size distributions are invariably unimodal in the absence of cooperative interactions, but when the latter interactions are attractive, the distributions are predicted to be bimodal below and unimodal above a critical temperature. Mean field and finite lattice predictions are found to be in globally good agreement with each other, except under near-critical conditions, and even there, the predicted average aggregate sizes and equilibrium constants are remarkably similar. Potential applications of these theoretical predictions to the analysis of experimental and molecular dynamics aggregation results are discussed.

Specific ion effects in amphiphile hydration and interface stabilization.

Specific ion effects can influence many processes in aqueous solutions: protein folding, enzyme activity, self-assembly, and interface stabilization. Ionic amphiphiles are known to stabilize the oil/water interface, presumably by dipping their hydrophobic tails into the oil phase while sticking their hydrophilic head groups in water. However, we find that anionic and cationic amphiphiles adopt strikingly different structures at liquid hydrophobic/water interfaces, linked to the different specific interactions between water and the amphiphile head groups, both at the interface and in the bulk. Vibrational sum frequency scattering measurements show that dodecylsulfate (DS(-)) ions do not detectably perturb the oil phase while dodecyltrimethylammonium (DTA(+)) ions do. Raman solvation shell spectroscopy and second harmonic scattering (SHS) show that the respective hydration-shells and the interfacial water structure are also very different. Our work suggests that specific interactions with water play a key role in driving the anionic head group toward the water phase and the cationic head group toward the oil phase, thus also implying a quite different surface stabilization mechanism.

On the cooperative formation of non-hydrogen-bonded water at molecular hydrophobic interfaces.

The unique structural, dynamical and chemical properties of air/water and oil/water interfaces are thought to play a key role in various biological, geological and environmental processes. For example, non-hydrogen-bonded ('dangling') OH groups--which create surface defects in water's hydrogen bonding network and are experimentally detected at both macroscopic (air/water or oil/water) and microscopic (dissolved hydrophobic molecule) interfaces--are thought to catalyse some chemical reactions. However, how the size, curvature or charge of the exposed hydrophobic surface influences water's propensity to form dangling OH defects has not yet been established quantitatively. Here we use Raman multivariate curve resolution to probe spectroscopically the hydrophobic hydration shell and, using a statistical multisite analysis, we show that such interfacial dangling OH structures are entropically stabilized and their formation is cooperative (the probability that a non-hydrogen-bonded OH group will form depends nonlinearly on the hydrophobic surface area). We thus expose an important difference between the chemical properties of molecular and macroscopic oil/water interfaces.

Analysis of molecular aggregation equilibria using random mixing statistics.

Aggregation processes in both the gas phase and aqueous solutions are analyzed by comparing aggregate size distributions obtained from molecular dynamics simulations with analytical predictions pertaining to a nonaggregating random mixture. The latter predictions are obtained by using the binomial distribution to predict the statistical properties of a uniformly mixed solution containing molecules of the same size and concentration as those in the solution of interest. Simulations are performed on systems containing neopentane dissolved in either methane, aqueous methanol, or aqueous NaI solutions. Comparisons of the theoretical and simulation results are used to both classify and quantify the influence of intermolecular interactions on such aggregation processes, including the equilibrium constants and thermodynamic functions pertaining to the partitioning of molecules between the bulk and first coordination shell of neopentane. Although the present results are primarily intended to describe and illustrate the random mixing analysis strategy, they also imply that neopentane has a greater tendency to aggregate with methane in the dense gas phase than with either methanol or iodide ions in aqueous solutions.

Interactions between halide anions and a molecular hydrophobic interface.

Interactions between halide ions (fluoride and iodide) and t-butyl alcohol (TBA) dissolved in water are probed using a recently developed hydration-shell spectroscopic technique and theoretical cluster and liquid calculations. High ignal-to-noise Raman spectroscopic measurements are combined with multivariate curve resolution (Raman-MCR) to reveal that while there is little interaction between aqueous fluoride ions and TBA, iodide ions break down the tetrahedral hydration-shell structure of TBA and produce a red-shift in its CH stretch frequency, in good agreement with the theoretical effective fragment potential (EFP) molecular dynamics simulations and hybrid quantum/EFP frequency calculations. The results imply that there is a significantly larger probability of finding iodide than fluoride in the first hydration shell of TBA, although the local iodide concentration is apparently not as high as in the surrounding bulk aqueous NaI solution.

Expulsion of ions from hydrophobic hydration shells.

Raman spectroscopy is combined with multivariate curve resolution to quantify interactions between ions and molecular hydrophobic groups in water. The molecular solutes in this study all have similar structures, with a trimethyl hydrophobic domain and a polar or charged headgroup. Our results imply that aqueous sodium and fluoride ions are strongly expelled from the first hydration shells of the hydrophobic (methyl) groups, while iodide ions are found to enter the hydrophobic hydration shell, to an extent that depends on the methyl group partial charge. However, our quantitative estimates of the corresponding ion binding equilibrium constants indicate that the iodide concentration in the first hydrophobic hydration shell is generally lower than that in the surrounding bulk water, and so an iodide ion cannot be viewed as having a true affinity for the molecular hydrophobic interface, but rather is less strongly expelled from such an interface than fluoride.

Distinguishing aggregation from random mixing in aqueous t-butyl alcohol solutions.

Raman spectroscopic measurements are combined with various multivariate curve resolution (Raman-MCR) strategies, to characterize the aggregation of t-butyl alcohol (TBA) in aqueous solutions. The resulting TBA solute-correlated (SC) spectra reveal perturbed water OH features arising from the hydration-shell of TBA as well as shifts in the TBA CH vibrational frequency arising from TBA-TBA interactions. Our results indicate that at low concentrations (below approximately 0.5 M), there is virtually no TBA aggregation. The first aggregates formed above 0.5 M remain highly hydrated, while those formed above approximately 2 M are significantly less hydrated. Comparisons with predictions pertaining to a randomly mixed (non-aggregating) solution indicate that below approximately 1 M there are fewer TBA-TBA contacts than would be present in a random mixture, thus implying that the thermodynamic stability of the first hydration-shell of TBA suppresses the formation of direct contact aggregates at low TBA concentrations. Our results further suggest that microheterogeneous domains containing many water-separated TBA-TBA contacts form near a TBA concentration of approximately 1 M, while at higher concentrations the TBA-rich domain size distribution may resemble that in a non-aggregating random mixture.