Interfacial chemical reactivity enhancement.

Interfacial enhancements of chemical reaction equilibria and rates in liquid droplets are predicted using a combined theoretical and experimental analysis strategy. Self-consistent solutions of reaction and adsorption equilibria indicate that interfacial reactivity enhancement is driven primarily by the adsorption free energy of the product (or activated complex). Reactant surface activity has a smaller indirect influence on reactivity due to compensating reactant interfacial concentration and adsorption free energy changes, as well as adsorption-induced depletion of the droplet core. Experimental air-water interfacial adsorption free energies and critical micelle concentration correlations provide quantitative surface activity estimates as a function of molecular structure, predicting an increase in interfacial reactivity with increasing product size and decreasing product polarity, aromaticity, and charge (but less so for anions than cations). Reactions with small, neutral, or charged products are predicted to have little reactivity enhancement at an air-water interface unless the product is rendered sufficiently surface active by, for example, interactions with interfacial water dangling OH groups, charge transfer, or voltage fluctuations.

The freezing behavior of aqueous n-alcohol nanodroplets.

We generate water-rich aerosols containing 1-propanol and 1-pentanol in a supersonic nozzle to study the effects of these solutes on the freezing behavior of water. Condensation and freezing are characterized by two complementary techniques, pressure trace measurements and Fourier Transform Infrared spectroscopy. When 1-pentanol and 1-propanol are present, condensation occurs at higher temperatures because particle formation from the vapor phase is enhanced by the decrease in interfacial free energy of mixed aqueous-alcohol critical clusters relative to those of pure water. FTIR results suggest that when ∼6 nm radius droplets freeze, the tetrahedral structure of the ice is well preserved up to an overall alcohol mole fraction of 0.031 for 1-propanol and 0.043 for 1-pentanol. In this concentration range, the ice nucleation temperature decreases continuously with increasing 1-propanol concentration, whereas the onset of freezing is not significantly perturbed by 1-pentanol up to a mole fraction of 0.03. Furthermore, once freezing starts the ice nucleation rates in the aqueous-alcohol droplets are very close to those for pure water. In contrast, at the highest mole fractions of either alcohol it is not clear whether droplets freeze to form crystalline ice since the final state of the particles cannot be adequately characterized with the available experimental techniques.

Surfactant aggregate size distributions above and below the critical micelle concentration.

Aggregate size distributions in an aqueous solution containing either charged or neutral surfactants are investigated using Raman multivariate curve resolution (Raman-MCR) spectroscopy and analyzed with the aid of a multi-aggregation chemical potential surface (MCPS) modeling strategy. Total least squares decompositions of the concentration-dependent Raman-MCR spectra are used to quantify the free and micelle surfactant populations, and the surfactant's C-H stretch frequency is used as a measure of its average aggregation state. MCPS predictions relate the experimental measurements to the underlying surfactant aggregate size distribution by fitting either the component concentrations or the average C-H frequency to MCPS predictions, and thus determine the critical micelle concentration (CMC) and estimate the corresponding micelle size and polydispersity. The Raman-MCR spectra of aqueous 1,2-hexanediol, sodium octanoate, and sodium dodecyl sulfate, measured both below and above CMC, provide critical tests of the assumed functional form of the MCPS and the presence of low-order premicellar aggregates. Our results indicate that the low-order aggregate population gradually emerges as the CMC is approached and then remains nearly concentration-independent after the appearance of micelles.

Influence of crowding on hydrophobic hydration-shell structure.

The influence of molecular crowding on water structure, and the associated crossover behavior, is quantified using Raman multivariate curve resolution (Raman-MCR) hydration-shell vibrational spectroscopy of aqueous tert-butyl alcohol, 2-butyl alcohol and 2-butoxyethanol solutions of variable concentration and temperature. Changes in the hydration-shell OH stretch band shape and mean frequency are used to identify the temperature at which the hydration-shell crosses over from a more ordered to less ordered structure, relative to pure water. The influence of crowding on the crossover is found to depend on solute size and shape in a way that is correlated with the corresponding infinitely dilute hydration-shell structure (and the corresponding first hydration-shell spectra are invariably very similar to pure water). Analysis of the results using a Muller-like two-state equilibrium between more ordered and less ordered hydration-shell structures implies that crossover temperature changes are dictated primarily by enthalpic stabilization of the more ordered hydration-shell structures.

Quantifying how step-wise fluorination tunes local solute hydrophobicity, hydration shell thermodynamics and the quantum mechanical contributions of solute-water interactions.

The ability to locally tune solute-water interactions and thus control the hydrophilic/hydrophobic character of a solute is key to control molecular self-assembly and to develop new drugs and biocatalysts; it has been a holy grail in synthetic chemistry and biology. To date, the connection between (i) the hydrophobicity of a functional group; (ii) the local structure and thermodynamics of its hydration shell; and (iii) the relative influence of van der Waals (dispersion) and electrostatic interactions on hydration remains unclear. We investigate this connection using spectroscopic, classical simulation and ab initio methods by following the transition from hydrophile to hydrophobe induced by the step-wise fluorination of methyl groups. Along the transition, we find that water-solute hydrogen bonds are progressively transformed into dangling hydroxy groups. Each structure has a distinct thermodynamic, spectroscopic and quantum-mechanical signature connected to the associated local solute hydrophobicity and correlating with the relative contribution of electrostatics and dispersion to the solute-water interactions.

Binding of divalent cations to acetate: molecular simulations guided by Raman spectroscopy.

In spite of the biological importance of the binding of Zn2+, Ca2+, and Mg2+ to the carboxylate group, cation-acetate binding affinities and binding modes remain actively debated. Here, we report the first use of Raman multivariate curve resolution (Raman-MCR) vibrational spectroscopy to obtain self-consistent free and bound metal acetate spectra and one-to-one binding constants, without the need to invoke any a priori assumptions regarding the shapes of the corresponding vibrational bands. The experimental results, combined with classical molecular dynamics simulations with a force field effectively accounting for electronic polarization via charge scaling and ab initio simulations, indicate that the measured binding constants pertain to direct (as opposed to water separated) ion pairing. The resulting binding constants do not scale with cation size, as the binding constant to Zn2+ is significantly larger than that to either Mg2+ or Ca2+, although Zn2+ and Mg2+ have similar radii that are about 25% smaller than Ca2+. Remaining uncertainties in the metal acetate binding free energies are linked to fundamental ambiguities associated with identifying the range of structures pertaining to non-covalently bound species.

Hydration-Shell Vibrational Spectroscopy.

Hydration-shell vibrational spectroscopy provides an experimental window into solute-induced water structure changes that mediate aqueous folding, binding, and self-assembly. Decomposition of measured Raman and infrared (IR) spectra of aqueous solutions using multivariate curve resolution (MCR) and related methods may be used to obtain solute-correlated spectra revealing solute-induced perturbations of water structure, such as changes in water hydrogen-bond strength, tetrahedral order, and the presence of dangling (non-hydrogen-bonded) OH groups. More generally, vibrational-MCR may be applied to both aqueous and nonaqueous solutions, including multicomponent mixtures, to quantify solvent-mediated interactions between oily, polar, and ionic solutes, in both dilute and crowded fluids. Combining vibrational-MCR with emerging theoretical modeling strategies promises synergetic advances in the predictive understanding of multiscale self-assembly processes of both biological and technological interest.

Hydrophobic but Water-Friendly: Favorable Water-Perfluoromethyl Interactions Promote Hydration Shell Defects.

Although perfluorination is known to enhance hydrophobicity and change protein activity, its influence on hydration-shell structure and thermodynamics remains an open question. Here we address that question by combining experimental Raman multivariate curve resolution spectroscopy with theoretical classical simulations and quantum mechanical calculations. Perfluorination of the terminal methyl group of ethanol is found to enhance the disruption of its hydration-shell hydrogen bond network. Our results reveal that this disruption is not due to the associated volume change but rather to the electrostatic stabilization of the water dangling OH···F interaction. Thus, the hydration shell structure of fluorinated methyl groups results from a delicate balance of solute-water interactions that is intrinsically different from that associated with a methyl group.

Water structural transformation at molecular hydrophobic interfaces.

Hydrophobic hydration is considered to have a key role in biological processes ranging from membrane formation to protein folding and ligand binding. Historically, hydrophobic hydration shells were thought to resemble solid clathrate hydrates, with solutes surrounded by polyhedral cages composed of tetrahedrally hydrogen-bonded water molecules. But more recent experimental and theoretical studies have challenged this view and emphasized the importance of the length scales involved. Here we report combined polarized, isotopic and temperature-dependent Raman scattering measurements with multivariate curve resolution (Raman-MCR) that explore hydrophobic hydration by mapping the vibrational spectroscopic features arising from the hydrophobic hydration shells of linear alcohols ranging from methanol to heptanol. Our data, covering the entire 0-100 °C temperature range, show clear evidence that at low temperatures the hydration shells have a hydrophobically enhanced water structure with greater tetrahedral order and fewer weak hydrogen bonds than the surrounding bulk water. This structure disappears with increasing temperature and is then, for hydrophobic chains longer than ~1 nm, replaced by a more disordered structure with weaker hydrogen bonds than bulk water. These observations support our current understanding of hydrophobic hydration, including the thermally induced water structural transformation that is suggestive of the hydrophobic crossover predicted to occur at lengths of ~1 nm (refs 5, 9, 10, 14).

Methane Hydration-Shell Structure and Fragility.

The influence of oily molecules on the structure of liquid water is a question of importance to biology and geology and many other fields. Previous experimental, theoretical, and simulation studies of methane in liquid water have reached widely conflicting conclusions regarding the structure of hydrophobic hydration-shells. Herein we address this question by performing Raman hydration-shell vibrational spectroscopic measurements of methane in liquid water from -10 °C to 300 °C (at 30 MPa, along a path that parallels the liquid-vapor coexistence curve). We show that, near ambient temperatures, methane's hydration-shell is slightly more tetrahedral than pure water. Moreover, the hydration-shell undergoes a crossover to a more disordered structure above ca. 85 °C. Comparisons with the crossover temperature of aqueous methanol (and other alcohols) reveal the stabilizing influence of an alcohol OH head-group on hydrophobic hydration-shell fragility.

Water-Mediated Hydrophobic Interactions.

Hydrophobic interactions are driven by the combined influence of the direct attraction between oily solutes and an additional water-mediated interaction whose magnitude (and sign) depends sensitively on both solute size and attraction. The resulting delicate balance can lead to a slightly repulsive water-mediated interaction that drives oily molecules apart rather than pushing them together and thus opposes their direct (van der Waals) attraction for each other. As a consequence, competing solute size-dependent crossovers weaken hydrophobic interactions sufficiently that they are only expected to significantly exceed random thermal energy fluctuations for processes that bury more than ∼1 nm(2) of water-exposed area.

Influence of Cononsolvency on the Aggregation of Tertiary Butyl Alcohol in Methanol-Water Mixtures.

The term cononsolvency has been used to describe a situation in which a polymer is less soluble (and so is more likely to collapse and aggregate) in a mixture of two cosolvents than it is in either one of the pure solvents. Thus, cononsolvency is closely related to the suppression of protein denaturation by stabilizing osmolytes. Here, we show that cononsolvency behavior can also influence the aggregation of tertiary butyl alcohol in mixtures of water and methanol, as demonstrated using both Raman multivariate curve resolution spectroscopy and molecular dynamics simulations. Our results imply that cononsolvency results from the cosolvent-mediated enhancement of the attractive (solvophobic) mean force between nonpolar groups, driven by preferential solvation of the aggregates, in keeping with Wyman-Tanford theory.

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.

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.

Fluorescence modeling for optimized-binary compressive detection Raman spectroscopy.

The recently-developed optimized binary compressive detection (OB-CD) strategy has been shown to be capable of using Raman spectral signatures to rapidly classify and quantify liquid samples and to image solid samples. Here we demonstrate that OB-CD can also be used to quantitatively separate Raman and fluorescence features, and thus facilitate Raman-based chemical analyses in the presence of fluorescence background. More specifically, we describe a general strategy for fitting and suppressing fluorescence background using OB-CD filters trained on third-degree Bernstein polynomials. We present results that demonstrate the utility of this strategy by comparing classification and quantitation results obtained from liquids and powdered mixtures, both with and without fluorescence. Our results demonstrate high-speed Raman-based quantitation in the presence of moderate fluorescence. Moreover, we show that this OB-CD based method is effective in suppressing fluorescence of variable shape, as well as fluorescence that changes during the measurement process, as a result of photobleaching.

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.

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.

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.

Influence of H+, OH- and salts on hydrophobic self-assembly.

In spite of the ubiquity of acid/base ions and salts in biological systems, their influence on hydrophobic self-assembly remains an open question. Here we use a combined experimental and theoretical strategy to quantify the influence of H+ and OH-, as well as salts containing Li+, Na+, Cl- and Br-, on the hydrophobic self-assembly of micelles composed of neutral oily 1,2-hexanediol surfactants. The distributions of aggregate sizes, both below and above the critical micelle concentration (CMC), are determined using Raman multivariate curve resolution (Raman-MCR) spectroscopy to quantify the multi-aggregation chemical potential surface (MCPS) that drives self-assembly. The results reveal that ions have little influence on the formation of hydrophobic contact dimers but can significantly drive high-order self assembly. Moreover, the hydration-shells of oily solutes are found to expel the above salt ions and OH-, but to attract H+, with wide-ranging implications.