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.

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.

Quantifying the Nearly Random Microheterogeneity of Aqueous tert-Butyl Alcohol Solutions Using Vibrational Spectroscopy.

The microheterogeneous structure of aqueous tert-butyl alcohol (TBA) solutions is quantified by combining experimental, simulations, and theoretical results. Experimental Raman multivariate curve resolution (Raman-MCR) C-H frequency shift measurements are compared with predictions obtained using combined quantum mechanical and effective fragment potential (QM/EFP) calculations, as well as with molecular dynamics (MD), random mixture (RM), and finite lattice (FL) predictions. The results indicate that the microheterogeneous aggregation in aqueous TBA solutions is slightly less than that predicted by MD simulations performed using either CHARMM generalized force field (CGenFF) or optimized parameters for liquid simulations all atom (OPLS-AA) force fields but slightly more than that in a self-avoiding RM of TBA-like molecules. The results imply that the onset of microheterogeneity in aqueous solutions occurs when solute contact free energies are about an order of magnitude smaller than thermal fluctuations, thus suggesting a fundamental bound of relevance to biological self-assembly.

Ion-Size Dependent Adsorption Crossover on the Surface of a Water Droplet.

The adsorption of ionic and neutral spherical solutes on the surface of a liquid water droplet are investigated using molecular dynamics simulations and theoretical analyses. The results reveal a crossover in the sign of the adsorption free energy as a function of ion size, with ions larger than iodide predicted to be increasingly surface active. Adsorption free energies are decomposed into competing energetic and entropic contributions arising from direct solute-water interaction energy and its fluctuations. The entropically driven surface activity of large ions is predicted to increase with ion size, while small ions are typically driven away from the interface by a more delicate balance of energetic and entropic contributions, with a nonmonotonic ion size dependence linked to the ion's hydration-shell structure and stability. The physical interpretation of the results is illuminated by comparisons with dielectric linear response and cavity formation predictions and implications to interfacial acidity and enhanced chemical reactivity are discussed.

Electric buzz in a glass of pure water.

Hydrogen bond charge transfer in water may have far-reaching chemical implications.

Expulsion of Hydroxide Ions from Methyl Hydration Shells.

The affinity of hydroxide ions for methyl hydration shells is assessed using a combined experimental and theoretical analysis of tert-butyl alcohol (TBA) dissolved in pure water and aqueous NaOH and NaI. The experimental results are obtained using Raman multivariate curve resolution (Raman-MCR) and a new three-component total least squares (Raman-TLS) spectral decomposition strategy used to highlight vibrational perturbations resulting from interactions between TBA and aqueous ions. The experiments are interpreted and extended with the aid of effective fragment potential molecular dynamics (EFP-MD) simulations, as well as Kirkwood-Buff calculations and octanol/water partition measurements, to relate TBA-ion distribution functions to TBA solubility changes. The combined experimental and simulation results reveal that methyl group hydration shells more strongly expel hydroxide than iodide anions, whose populations near the methyl groups of TBA are predicted to be correlated with sodium counterion localization near the TBA hydroxyl group.

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 Methylene Fluorination and Chain Length on the Hydration Shell Structure and Thermodynamics of Linear Diols.

The interplay between the local hydration shell structure, the length of hydrophobic solutes, and their identity (perfluorinated or not) remains poorly understood. We address this issue by combining Raman-multivariate curve resolution (Raman-MCR) spectroscopy, simulation, and quantum-mechanical calculations to quantify the thermodynamics and the first principle interactions behind the formation of defects in the hydration shell of alkyl-diol and perfluoroalkyl-diol chains. The hydration shell of the fluorinated diols contains substantially more defects than that of the nonfluorinated diols; these defects are water hydroxy groups that do not donate hydrogen bonds and which either point to the solute (radial-dangling OH) or not (nonradial-dangling OH). The number of radial-dangling OH defects per carbon decreases for longer chains and toward the interior of the fluorinated diols, mainly due to less favorable electrostatics and exchange interactions; nonradial-dangling OH defects per carbon increase with chain length. In contrast, the hydration shell of the nonfluorinated diols only contains radial-dangling defects, which become more abundant toward the center of the chain and for larger chains, predominantly because of more favorable dispersion interactions. These results have implications for how the folding of macromolecules, ligand binding to biomacromolecules, and chemical reactions at water-oil interfaces could be modified through the introduction of fluorinated groups or solvents.

Hydration and Seamless Integration of Hydrogen Peroxide in Water.

Raman multivariate curve resolution is used to decompose the vibrational spectra of aqueous hydrogen peroxide (H2O2) into pure water, dilute H2O2, and concentrated H2O2 spectral components. The dilute spectra reveal four sub-bands in the OH stretch region, assigned to the OH stretch and Fermi resonant bend overtone of H2O2, and two nonequivalent OH groups on water molecules that donate a hydrogen bond to H2O2. At high concentrations, a spectral component resembling pure H2O2 emerges. Our results further demonstrate that H2O2 perturbs the structure of water significantly less than either methanol or sodium chloride of the same concentration, as evidenced by comparing the hydration-shell spectra of tert-butyl alcohol dissolved in the three aqueous solutions.

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.

Complementarity of FT-IR and Raman spectroscopies for the species discrimination of meat and bone meals related to lipid molecular profiles.

The objective of this study is to realise the successful species discrimination of meat and bone meals (MBMs) based on the complementarity of FT-IR and Raman spectra. The spectral variation of typical lipid profiles on FT-IR and Raman spectra of MBMs as well as the chemical structure-related principle of FT-IR and Raman spectroscopies related to lipid characteristics were investigated. Lipids from MBMs were separately collected by FT-IR and Raman spectroscopes, which illustrated both spectra (1800 ~ 900 cm-1) presented different typical lipid peaks. The combination of FT-IR and Raman spectra contributed to establish the more reliable and robust species discrimination model compared to single FT-IR or Raman spectra due to more detailed and integrated molecular vibration information. Degree of unsaturation and cis/trans fatty acid contents were considered the important chemical structure-related factors for ideal species discrimination. Complementation of FT-IR and Raman spectra performed synergistic enhancement to the species discrimination with diverse contributions.

Spectroscopic and Structural Characterization of Water-Shared Ion-Pairs in Aqueous Sodium and Lithium Hydroxide.

The structures of the ion-pairs formed in aqueous NaOH and LiOH solutions are elucidated by combining Raman multivariate curve resolution (Raman-MCR) experiments and ab initio molecular dynamics (AIMD) simulations. The results extend prior findings to reveal that the initially formed ion-pairs are predominantly water-shared, with the hydroxide ion retaining its full first hydration-shell, while direct contact ion-pairing only becomes significant at higher concentrations. Our results confirm previous experiments and simulations indicating greater ion-pairing in aqueous LiOH than NaOH as well as at high temperatures. Our results further imply that NaOH and LiOH ion-pairing free energies have an approximately linear (rather than square-root) dependence on ion concentration (in the molar range), with positive enthalpies and entropies that increase with concentration, thus implying that water-mediated interactions enthalpically disfavor and entropically favor ion-pair formation.

Spectroscopically Quantifying the Influence of Salts on Nonionic Surfactant Chemical Potentials and Micelle Formation.

The influence of two salts (NaSCN and Na2SO4) on the micellization of a nonionic surfactant (1,2-hexanediol) is quantified using Raman multivariate curve resolution spectroscopy, combined with a generalized theoretical analysis of the corresponding chemical potential changes. Although the SCN- and SO42- anions are on opposite ends of the Hofmeister series, they are both found to lower the critical micelle concentration. Our combined spectroscopic and theoretical analysis traces these observations to the fact that in both salt solutions the ions have a greater affinity for (or are less strongly expelled from) the hydration shell of the micelle than the free surfactant monomer, as quantified using the corresponding chemical potentials and Wyman-Tanford coefficients. This probe-free experimental and theoretical analysis strategy may readily be extended to micelle formation processes involving other surfactants, salts, and cosolvents, as well as to other sorts of aggregation and binding processes.

Optimally pooled viral testing.

It has long been known that pooling samples may be used to reduce the total number of tests required in order to identify each infected individual in a population. Pooling is most advantageous in populations with low infection (positivity) rates, but is expected to remain better than non-pooled testing in populations with infection rates up to 30%. For populations with infection rates lower than 10%, additional testing efficiency may be realized by performing a second round of pooling to test all the samples in the positive first-round pools. The present predictions are validated by recent COVID-19 (SARS-CoV-2) pooled testing and detection sensitivity measurements performed using non-optimal pool sizes, and quantify the additional improvement in testing efficiency that could have been obtained using optimal pooling. Although large pools are most advantageous for testing populations with very low infection rates, they are predicted to become highly non-optimal with increasing infection rate, while pool sizes smaller than 10 remain near-optimal over a broader range of infection rates.

Binding-Induced Unfolding of 1-Bromopropane in α-Cyclodextrin.

Raman multivariate curve resolution vibrational spectroscopy and X-ray crystallography are used to quantify changes in the gauche-trans conformational equilibrium of 1-bromopropane (1-BP) upon binding to α-cyclodextrin (α-CD). Both conformers of 1-BP are found to bind to α-CD, although binding favors the unfolded trans conformation. Temperature-dependent measurements of the binding-induced change in the 1-BP conformation equilibrium constant indicate that the trans conformer is both enthalpically and entropically stabilized in the host cavity.

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.

Spontaneous drying of non-polar deep-cavity cavitand pockets in aqueous solution.

There are many open questions regarding the hydration of solvent-exposed non-polar tracts and pockets in proteins. Although water is predicted to de-wet purely repulsive surfaces and evacuate crevices, the extent of de-wetting is unclear when ubiquitous van der Waals interactions are in play. The structural simplicity of synthetic supramolecular hosts imbues them with considerable potential to address this issue. To this end, here we detail a combination of densimetry and molecular dynamics simulations of three cavitands, coupled with calorimetric studies of their complexes with short-chain carboxylates. Our results reveal the range of wettability possible within the ostensibly identical cavitand pockets-which differ only in the presence and/or position of the methyl groups that encircle the portal to their non-polar pockets. The results demonstrate the ability of macrocycles to template water cavitation within their binding sites and show how the orientation of methyl groups can trigger the drying of non-polar pockets in liquid water, which suggests new avenues to control guest complexation.

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.