Temperature-dependent structure of methanol-water mixtures on cooling: X-ray and neutron diffraction and molecular dynamics simulations

Methanol-water liquid mixtures have been investigated by high-energy synchrotron X-ray and neutron diffraction at low temperatures. We are thus able to report the first complete sets of both X-ray and neutron weighted total scattering structure factors over the entire composition range (at 12 different methanol concentrations (xM) from 10 to 100 mol%) and at temperatures from ambient down to the freezing points of the mixtures. The new diffraction data may later be used as reference in future theoretical and simulation studies. The measured data are interpreted by molecular dynamics simulations, in which the all atom OPLS/AA force field model for methanol is combined with both the SPC/E and TIP4P/2005 water potentials. Although the TIP4P/2005 water model was found to be somewhat more successful, both combinations provide at least semi-quantitative agreement with measured diffraction data. From the simulated particle configurations, partial radial distribution functions, as well as various distributions of the number of hydrogen bonds have been determined. As a general trend, the average number of hydrogen bonds increases upon cooling. However, the number of hydrogen bonds between methanol molecules slightly decreases with lowering temperatures in the concentration range between ca. 30 and 60 mol% alcohol content. The same is valid for water-water hydrogen bonds above 70 mol% of methanol content, from room temperature down to 193 K

How Water's Properties Are Encoded in Its Molecular Structure and Energies.

How are water's material properties encoded within the structure of the water molecule? This is pertinent to understanding Earth's living systems, its materials, its geochemistry and geophysics, and a broad spectrum of its industrial chemistry. Water has distinctive liquid and solid properties: It is highly cohesive. It has volumetric anomalies-water's solid (ice) floats on its liquid; pressure can melt the solid rather than freezing the liquid; heating can shrink the liquid. It has more solid phases than other materials. Its supercooled liquid has divergent thermodynamic response functions. Its glassy state is neither fragile nor strong. Its component ions-hydroxide and protons-diffuse much faster than other ions. Aqueous solvation of ions or oils entails large entropies and heat capacities. We review how these properties are encoded within water's molecular structure and energies, as understood from theories, simulations, and experiments. Like simpler liquids, water molecules are nearly spherical and interact with each other through van der Waals forces. Unlike simpler liquids, water's orientation-dependent hydrogen bonding leads to open tetrahedral cage-like structuring that contributes to its remarkable volumetric and thermal properties

Water in Protein Cavities: Free Energy, Entropy, Enthalpy, and its Influences on Protein Structure and Flexibility

Complexes of the antibiotics novobiocin and clorobiocin with DNA gyrase are illustrative of the importance of bound water to binding thermodynamics. Mutants resistantto novobiocin as well as those with a decreased affinity for novobiocin over clorobiocinboth involve a less favorable entropy of binding, which more than compensates for amore favorable enthalpy, and additional water molecules at the proteinligandinterface.Free energy, enthalpy, and entropy for these water molecules were calculated by thermodynamicintegration computer simulations. The calculations show that addition of thewater molecules is entropically unfavorable, with values that are comparable to the measuredentropy differences. The free energies and entropies correlate with the change inthe number of hydrogen bonds due to the addition of water molecules.To examine the wide variety of cavities available to water molecules inside proteins,a model of the protein cavities is developed with the local environment treated at atomicdetail and the nonlocal environment treated approximately. The cavities are then changedto vary in size and in the number of hydrogen bonds available to a water molecule insidethe cavity. The free energy, entropy, and enthalpy change for the transfer of a watermolecule to the cavity from the bulk liquid is calculated from thermodynamic integration.The results of the model are close to those of similar cavities calculated using the fullprotein and solvent environment. As the number of hydrogen bonds resulting from theaddition of the water molecule increases, the free energy decreases, as the enthalpic gainof making a hydrogen bond outweighs the entropic cost. Changing the volume of thecavity has a smaller effect on the thermodynamics. Once the hydrogen bond contributionis taken into account, the volume dependence on free energy, entropy, and enthalpy issmall and roughly the same for a hydrophobic cavity as a hydrophilic cavity.The influences of bound water on protein structure and influences are also evaluatedby performing molecular dynamics simulation for proteins with and without boundwater. Four proteins are simulated, the wildtypebovine pancreatic trypsin inhibitor(BPTI), the wildtypehen egg white lysozyme (HEWL), and two variants of the wildtypeStaphylococcal nuclease (SNase), PHS and PHS/V66E. The simulation reveals that allthese four proteins suffer structural changes upon the removing of bound water molecules,as indicating by their increased RMSD values with respect to the crystal structures. Threeout of the four proteins, BPTI, HEWL, and the PHS mutant of SNase have increased flexibility,while no apparent flexibility change is seen in the PHS/V66E variant of SNase

Water in Protein Cavities: Free Energy, Entropy, Enthalpy, and its Influences on Protein Structure and Flexibility

Complexes of the antibiotics novobiocin and clorobiocin with DNA gyrase are illustrative of the importance of bound water to binding thermodynamics. Mutants resistantto novobiocin as well as those with a decreased affinity for novobiocin over clorobiocinboth involve a less favorable entropy of binding, which more than compensates for amore favorable enthalpy, and additional water molecules at the proteinligandinterface.Free energy, enthalpy, and entropy for these water molecules were calculated by thermodynamicintegration computer simulations. The calculations show that addition of thewater molecules is entropically unfavorable, with values that are comparable to the measuredentropy differences. The free energies and entropies correlate with the change inthe number of hydrogen bonds due to the addition of water molecules.To examine the wide variety of cavities available to water molecules inside proteins,a model of the protein cavities is developed with the local environment treated at atomicdetail and the nonlocal environment treated approximately. The cavities are then changedto vary in size and in the number of hydrogen bonds available to a water molecule insidethe cavity. The free energy, entropy, and enthalpy change for the transfer of a watermolecule to the cavity from the bulk liquid is calculated from thermodynamic integration.The results of the model are close to those of similar cavities calculated using the fullprotein and solvent environment. As the number of hydrogen bonds resulting from theaddition of the water molecule increases, the free energy decreases, as the enthalpic gainof making a hydrogen bond outweighs the entropic cost. Changing the volume of thecavity has a smaller effect on the thermodynamics. Once the hydrogen bond contributionis taken into account, the volume dependence on free energy, entropy, and enthalpy issmall and roughly the same for a hydrophobic cavity as a hydrophilic cavity.The influences of bound water on protein structure and influences are also evaluatedby performing molecular dynamics simulation for proteins with and without boundwater. Four proteins are simulated, the wildtypebovine pancreatic trypsin inhibitor(BPTI), the wildtypehen egg white lysozyme (HEWL), and two variants of the wildtypeStaphylococcal nuclease (SNase), PHS and PHS/V66E. The simulation reveals that allthese four proteins suffer structural changes upon the removing of bound water molecules,as indicating by their increased RMSD values with respect to the crystal structures. Threeout of the four proteins, BPTI, HEWL, and the PHS mutant of SNase have increased flexibility,while no apparent flexibility change is seen in the PHS/V66E variant of SNase

Modeling Molecular Interactions in Water: From Pairwise to Many-Body Potential Energy Functions.

Almost 50 years have passed from the first computer simulations of water, and a large number of molecular models have been proposed since then to elucidate the unique behavior of water across different phases. In this article, we review the recent progress in the development of analytical potential energy functions that aim at correctly representing many-body effects. Starting from the many-body expansion of the interaction energy, specific focus is on different classes of potential energy functions built upon a hierarchy of approximations and on their ability to accurately reproduce reference data obtained from state-of-the-art electronic structure calculations and experimental measurements. We show that most recent potential energy functions, which include explicit short-range representations of two-body and three-body effects along with a physically correct description of many-body effects at all distances, predict the properties of water from the gas to the condensed phase with unprecedented accuracy, thus opening the door to the long-sought "universal model" capable of describing the behavior of water under different conditions and in different environments

Investigating Anions and Hydrophobicity of Deep Eutectic Solvents by Experiment and Computational Simulation

Deep eutectic solvents are a new generation of ionic liquid-like solvents formed by combining hydrogen bond acceptor with hydrogen bond donor which result in the depression of the melting point of the solvent. Like ionic liquids, anions play a critical role in tuning the polarity, physicochemical properties, and thermodynamic behavior of deep eutectic solvent (DES). Choline chloride is the most widely used quaternary ammonium salt (QAS) in the literature and has remarkable advantages from reduced cost to low toxicity and volatility. Choline bromide and choline iodide are other QAS that have not been used often for DES synthesis and applications, probably with the opinion that chlorides form stronger hydrogen bonds. Developing new DES from these anions will broaden the scope of green solvents selection for diverse applications. The first objective of this dissertation looked into the synthesis and characterization of DES from choline chloride, choline bromide, and choline iodide with malic acid, malonic acid, and urea. Also, we studied the thermodynamic behavior of the solvents by measuring their vapor pressure, density, and infinite activity coefficient in polar and nonpolar solvents. The results show that choline bromide can sometimes be used to replace choline chloride because both QAS share comparable physicochemical behavior. In most cases, choline iodide forms weaker hydrogen bonding with the donors leading to the formation of a solid at room temperature. Nevertheless, all the solvents have melting temperature below 100℃. In summary, DES can be synthesized from the choline cation bonded with the halides, with the melting point and nature of the solvent dependent on the hydrogen bond donor (HBD). Secondly, despite the rapid rise in publications and applications since their inception in 2001, most of the DES synthesized are generally hydrophilic. The low cost, low toxicity, and bioavailability of DES make the solvent green and sustainable for diverse applications. Conversely, the hydrophilicity of DES practically limits their application to only polar compounds, which is a major drawback of the solvent. For the past three years, hydrophobic deep eutectic solvents (HDES) have emerged as alternative extractive media capable of extracting nonpolar molecules from aqueous environments. In chapter three of this dissertation, the general objective was to design a cost-effective hydrophobic DES from choline chloride and fatty acids. Varying the alkyl chain of the fatty acid broadened our understanding about the role of HBD in DES and also helped in the tunability of the HDES polarity. Due to the infancy of HDES, for the first time, this dissertation expands on the design, synthesis, and physicochemical characterization of HDES developed from choline chloride and fatty acids. To understand the hydrogen-bonding pattern of HDES, a multivariate unsupervised principal component analysis was used to cluster HDES by using known DES as a control. The HDES was able to extract about 70% of piperine, a bioactive compound from Piper nigrum. In the future, it is believed that HDES could replace the majority of toxic organic solvents used for analytical purposes. Lastly, the electronic and molecular properties of the HDES synthesized were studied by using a solvatochromic molecular probes and a hybrid density functional theory at 6-31G (d) basis set. The empirical polarity assay and quantum theoretical calculations showed that decreasing the alkyl chain length of the hydrogen bond donor increases viscosity of the DES. Optimization of the DES molecular geometry indicates a reduced bond angle between the C15-O16-H17 atoms in choline chloride, signifying a change in electronegativity of the central atom (O16) during DES formation. From our results, we predict a possible molecular reorientation between the donor and the acceptor molecules during DES formation. The combined theoretical calculations and experimental approaches are useful to establish clear correlations between electronic parameters and physiochemical parameters like polarity, viscosity, and stability of carboxylic acid-DES and can be extended to other conventional solvents

Fluctuation solution theory

Doctor of PhilosophyDepartment of ChemistryPaul E. SmithThe Kirkwood-Buff (KB) theory of solutions, published in 1951, established a route from integrals over radial (pair) distribution functions (RDFs) in the grand canonical ensemble to a set of thermodynamic quantities in an equivalent closed ensemble. These “KB integrals” (KBIs) can also be expressed in terms of the particle-particle (i.e., concentration or density) fluctuations within grand canonical ensemble regions. Contributions by Ben-Naim in 1977 provided the means to obtain the KBIs if one already knew the set of thermodynamic quantities for the mixture of interest; that is, he provided the inversion procedure. Thus, KB theory provides a two-way bridge between local (microscopic) and global (bulk/thermodynamic) properties. Due to its lack of approximations, its wide ranging applicability, and the absence of a competitive theory for rigorously understanding liquid mixtures, it has been used to understand solution microheterogeneity, solute solubility, cosolvent effects on biomolecules, preferential solvation, etc. Here, after using KB theory to test the accuracy of pair potentials, we present and illustrate two extensions of the theory, resulting in a general Fluctuation Solution Theory (FST). First, we generalize KB theory to include two-way relationships between the grand canonical ensemble’s particle-energy and energy-energy fluctuations and additional thermodynamic quantities. This extension allows for non-isothermal conditions to be considered, unlike traditional KB theory. We illustrate these new relationships using analyses of experimental data and molecular dynamics (MD) simulations for pure liquids and binary mixtures. Furthermore, we use it to obtain conformation-specific infinitely dilute partial molar volumes and compressibilities for proteins (other properties will follow) from MD simulations and compare the method to a non-FST method for obtaining the same properties. The second extension of KB theory involves moving beyond doublet particle fluctuations to additionally consider triplet and quadruplet particle fluctuations, which are related to derivatives of the thermodynamic properties involved in regular KB theory. We present these higher order fluctuations obtained from experiment and simulation for pure liquids and binary mixtures. Using the newfound experimental third and fourth cumulants of the distribution of particles in solution, which can be extracted from bulk thermodynamic data using this extension, we also probe particle distributions’ non-Gaussian nature