Specific ion effects on protein interfaces have been observed for many years, but yet comprehensive explanations regarding the mechanism by which ions interact with proteins and more general aqueous interfaces are still under investigation. Realistically, ion specificity on protein stability is due to numerous contributions and interactions between the solution and protein. However, the most important contribution is arguably the hydrophobic effect, specifically the change in free energy when water molecules are liberated from the interfacial region upon protein folding. In the work presented here, the effects of different ions on the critical micelle concentration (CMC) of 1, 2 –Hexanediol were examined to study salt effects on hydrophobicity by the means of fluorescence spectroscopy. Our results show that anions and cations do exhibit the specific effects on hydrophobic interactions. However, the origin of these specific ion effects different for cations and anions. Cation specific effects are caused by their ability to form cavities in solution, while anion specific effects arise from their ability to interact with the interface. These results are of interest to the researchers in the protein folding field, providing significant experimental hydrophobicity data necessary for theoretical biologists that are attempting to predict protein structures. / February 2015

archives@tulane.edu / Solubility is the ability of a molecule to favorably interact with a solvent. While seemingly simple in application many phenomena arise from knife-edge like conditions between solubility and insolubility. Herein, three of these phenomena; co-non-solvency, the hydrophobic effect, and the direct and reverse Hofmeister effects are investigated in detail to parse out a mechanistic view of solubility in each case. The first phenomenon, co-non-solvency, is the insolubility of a thermo-responsive polymer and a mixture of two good cosolvents. Host-guest systems are used to probe small molecule interactions in the presence of cosolvents for co-non-solvent effects. The second phenomenon, the hydrophobic effect, is often colloquially described as “oil and water do not mix.” However, this is much more complex when diving into the energetic contributions. Host-guest systems are used to determine structural effects novel hosts and guests have on the hydrophobic effect in collaboration with the computational community. The third phenomenon, the Hofmeister effects, are explored through the fine tuning of solubility of lysozyme through the addition of sodium perchlorate in varying pHs. This is used to determine a mechanistic view of protein solubility in the presence of salts. / 1 / Nicholas Ernst

Abstract: Greener synthetic routes for producing organic molecules are desirable to reduce environmental pollution and lower manufacturing costs.2 In this context, Sharpless & co-workers reported that it is possible to achieve dramatic rate enhancements in a number of cycloaddition reactions, if they were conducted in vigorously mixed oil-water emulsions instead of bulk organic solvents.1 These interfacial reactions – which came to be known as “on-water” reactions – thus present a tantalizing prospect for green chemistry. However, despite many experimental and theoretical studies along this theme, a clear understanding of the governing factors and mechanisms remains unavailable. For instance, proposed mechanisms vary from dangling hydrogen bonds stabilizing transition states, to the specific adsorption of hydroxide ions at the water-organic interface, and the partial dissolution of reactants in water leading to products.3,4,5Additional effects include sharp variations in dielectric constants and hydration levels across the interface and hydrodynamic effects during vigorous stirring. In this thesis, we investigate a Diels-Alder reaction between two water-insoluble reactants – trans,trans-2,4-hexadienyl acetate and N-propylmaleimide– to disentangle the contributions of bulk reactions from interfacial reactions. We compare the conversion of reactants into products in the following scenarios: pure reactants (i) mixed into each other (neat condition), (ii) dissolved in hexane, (iii) dissolved in hexane and vigorously stirred with water (1:1 v/v), and (iv) dissolved in hexane and vigorously stirred in water-methanol mixtures. In addition to vigorously-stirred emulsions that produce polydisperse emulsions, we designed and developed microfluidic devices that allowed us to precisely controlled the water-organic interfacial area. With this6 device, we pin-point interfacial effects on the reaction rates.

Various studies suggest tannins act as antioxidants, anticarcinogens, cardio-protectants, anti-inflammatory agents, and antimicrobials. However, more investigation is needed to examine the bioavailability of tannins. Tannins bind to salivary peptides by hydrophilic and hydrophobic mechanisms. Electrospray Ionization Mass Spectrometry (ESI-MS) has been used to assess both hydrophilic and hydrophobic components of protein complexes. ESI-MS could potentially be an effective tool for screening the bioavailability of tannins. Weaker binding tannins are predicted to be more highly absorbed by the body, and should therefore exhibit greater bioavailability. Rannulu and Cole have used ESI-MS to measure binding affinities of procyanidin tannin stereoisomers for salivary peptides in aqueous solution. The condensed tannins procyanidin B1, B2, B3, and B4 demonstrated significantly different binding affinities (binding strengths) for the Histatin 5 salivary peptide. The procyanidin-Histatin 5 binding mechanisms in the ESI-MS experiments by Rannulu and Cole were investigated using the FRED docking program combined with molecular dynamics optimization in the AMBER software suite. The simulations suggest residual liquid-phase binding interactions in procyanidin-Histatin 5 complexes are maintained in the gas phase under conditions resembling those in ESI-MS experiments, though the gas-phase interaction energies were enhanced. Increased hydrogen bonding and decreased π-π stacking interactions were also detected in gas versus liquid-phase procyanidin-Histatin 5 complexes. In addition, simulation results suggest multiple conformations of procyanidins bind Histatin 5 at several sites and procyanidin binding does not fix the Histatin 5 peptide backbone. The simulations agree with previous studies which indicate aromatic Histatin 5 residues are responsible for procyanidin-Histatin 5 binding and tannins can bind salivary peptides in multiple conformations. The effects of Hofmeister salts on complexation of an amphiphilic guest adamantane carboxylic acid to the hydrophobic surface of a deep-cavity cavitand have been investigated by Gibb et al. Adamantane-cavitand binding was found to be largely enthalpically driven, though adamantane binding in the presence of the salting-in anions perchlorate and thiocyanate was entropically driven. Gibb et al. also found that perchlorate-cavitand binding was enthalpically favorable, though entropically unfavorable. Potential-of-mean-force (PMF) calculations for perchlorate-cavitand and thiocyanate-cavitand complexation were performed using umbrella sampling with a modified version of the sander module from the Amber 9 software suite to further investigate the thermodynamic properties of Hofmeister-anion binding to the hydrophobic cavitand. The enthalpy for salting-in anion-cavitand complexation was calculated from the potential energy difference between the bound and unbound state (the potential energy of binding) along with the entropy. The binding entropy and enthalpy were also calculated using a finite difference approximation to the entropy. The enthalpy for perchlorate-cavitand complexation calculated from the binding energy and the finite difference approximation to the entropy was favorable with an unfavorable entropy. The binding enthalpy and entropy for thiocyanate-cavitand complexation calculated from the binding energy and finite difference approximation to the entropy were unfavorable and favorable, respectively, perhaps due to a classical hydrophobic effect. The orientation of the ligand, the number of water molecules displaced from the ligand and cavitand upon complexation, and the number of nearest-neighbor atom contacts between the ligand and the cavitand were also calculated. Additionally, the energetics of various interactions involved in salting-in anion-cavitand complexation including the anion-cavitand, anion-water, cavitand-water, and water-water interactions were assessed, though the data were inconclusive.

Temperature, pressure, and length scale dependence of the solvation of simple solvophobic solutes is investigated in the Jagla liquid, a simple liquid consisting of particles that interact via a spherically symmetric potential combining hard and soft core interactions. The results are compared with identical calculations for a model of a typical atomic liquid, the Lennard-Jones (LJ) potential, and with predictions for hydrophobic solvation in water using the recently developed cavity equation of state and the extended simple point charge model. We find that the Jagla liquid captures the qualitative thermodynamic behavior of hydrophobic hydration as a function of temperature and pressure for both small and large length scale solutes. In particular, for both the Jagla liquid and water, we observe temperature-dependent enthalpy and entropy of solvation for all solute sizes as well as a negative solvation entropy for sufficiently small solutes at low temperature. This feature of water-like solvation is distinct from the strictly positive and temperature independent enthalpy and entropy of cavity solvation observed in the Lennard-Jones fluid. The results suggest that a competition between two energy scales that favors low-density, open structures as temperature is decreased is an essential interaction of a liquid that models hydrophobic hydration. In addition the Jagla liquid dewets surfaces of large radii of curvature less readily than the Lennard-Jones liquid, and the so-called ``length scale crossover'' in solvation, whereby solvation free energies change from scaling with the solute volume to scaling with the solute surface area, occurs at length scales that are larger relative to the solvent size. Both features reflect a greater flexibility or elasticity in the Jagla liquid structure than that of a typical liquid, similar to water's ability to maintain its hydrogen bond network. The implications of the differences in crossover behavior between water-like and typical liquids are examined in the context of a simple thought experiment on the aggregation of solvophobic solutes that builds on ideas from Chandler and Rajamani et al. We find that water-like crossover behavior exposes a size range of solvophobic aggregates to destabilization upon cooling and pressurizing, which may thereby precipitate phenomena such as cold and pressure denaturation of proteins. Statistics of density fluctuations, void space, and pair distributions are analyzed for molecular-scale volumes. The pair distribution functions are used to provide an estimate of the size of the Jagla particle with a physical basis. The void distributions are observed to be distinct in the three liquids, with low temperature distributions in the LJ and Jagla liquids demonstrating a high degree of skewness. The void distributions observed in LJ liquid are hard sphere-like, while those of water and the Jagla liquid exhibit a higher degree of density inhomogeneity relative to a hard sphere system. The well-known Gaussian behavior of density fluctuations in molecular volumes in water is not generally observed in other liquids, as evidenced by the fact that this behavior is not consistently observed in either the LJ or the Jagla liquids. An exploratory study of the effects of explicit solvent on the sequence energy landscape of model heteropolymers has been performed. For a fixed set of configurations, the energy landscape of all possible sequences taken from a two letter alphabet consisting of only solvophilic and solvophobic monomers is characterized at different solvent temperatures. Non-trivial solvent and temperature effects are manifest in the distribution of sequences, confirming that the negation of these effects may have profound consequences on designability. / text

No description available.

Water is a simple molecule but is an essential part of life. One key aspect of the properties of water is the hydrophobic effect, and whilst there is an appreciation of this phenomenon at the macro-scale (raindrops falling off leaves) and the micro-scale (the structure of cellular systems), a complete understanding at the molecular level still eludes science. Addressing this issue, our studies involve synthetic supramolecular compounds that assemble in water via the hydrophobic effect. First of all, a novel water-soluble deep-cavity cavitand was synthesized. It possesses four endo methyl groups on top rim of the cavitand, eight water-solubilizing carboxylic acid groups coated on the cavitand exterior, and a relatively large hydrophobic interior. Compared to a previous well-studied water-soluble deep-cavity cavitand octa-acid (OA), this novel cavitand (TEMOA) possesses a non-monotonic assembly profile in the presence of a homologous series of straight-chain alkanes. Three supramolecular species were observed: 1:1, 2:2, and 2:2 and they are approximately isoenergetic. Second, we examined the guest-controlled self-sorting in assemblies. A mixture of OA and TEMOA formed hetero-capsular complex driven by the hydrophobic effect. The extent of homo- or hetero-dimerization is intimately tied to the size of the guest being encapsulated. TEMOA is less predisposed to dimerize than OA, thus TEMOA possesses the ability to form various self-assembled states, such as tetrameric and hexameric assemblies. Furthermore, we also discussed our observation of how external stimuli such as changing the nature or concentration of a co-solute salt influences a unique, unusual transition from one assembled state to another.

Neste trabalho estudamos o efeito hidrofóbico no sistema benzenoágua. Nossa estratégia é avaliar as propriedades das ligações de hidrogênio entre as moléculas de água nas proximidades da molécula e benzeno. Utilizamos as ferramentas da mecânica quântica e o método de simulação computacional para este estudo. A análise estrutural e energética detalhada dos clusters benzenoágua mostra que a ligação de hidrogênio é mais forte quando na presença do benzeno. A investigação pelo método de simulação Monte Carlo corrobora estas conclusões e ainda fornece os efeitos da variação de tempeatura. Verificamos que o aumento da temperatura afeta todas as moléculas aumentando a desordem líquida, no entanto, constatamos a manutenção de uma estrutura de ligações de hidrogênio mais fortes as proximidades do benzeno. A interação entre duas moléculas de benzeno também foi analisada, mostrando que a interação benzenobenzeno é bem mais forte na presença da água. / The hydrophobic effect is studied for the benzene-water system. The properties of the hydrogen bond between the water molecules around the benzene is evaluated using both classical and quantum mechanical methods. Hydrophobic hydration analysis shows that the hydrogen bond interaction is stronger in the presence of benzene. This is verified both by ab initio quantum mechanical methods and classical Monte Carlo simulation. Temperature dependence is investigated. Although increasing temperature increases the disorder the hydrogen bonds between the water molecules are still stronger for those in the proximities of the benzene. Hydrophobic interaction is also investigated. It is seen that the benzene-benzene interaction is stronger in the water environment.

The hydrophobic effect has been a topic of research for decades, not only due to its importance as the primary building block of much of chemistry (it dictates which solvent can dissolve which solutes) and biology (guiding protein binding and gene expression) but also due to it being a fundamental physical process. The commonly held opinion is that 'like dissolve like', implying polar substances can readily mix with other polar substances, and similarly for apolar ones, but polar and apolar would separate and tend to stay isolated from one another (like oil in water). We have developed a quantitative imaging method that can be used in tandem with Raman spectroscopy in order to investigate the effect of high pressure on a model hydrophobic system - water and methane. Our study revealed an unexpectedly large increase in the amount of methane that can readily mix with water once a rather modest pressure has been applied to the system. Thus, the solubility of CH4 in H2O starts abruptly increasing at 1.3 GPa and reaches a maximum of 44(3) mole % at 2.1 GPa, showing no pressure dependence upon further compression. We have tried to reproduce the observed experimental behaviour using classical molecular dynamics simulations deploying a range of widely used water potentials (SPC/E, TIP4P, TIP3P), but unfortunately no quantitative or even qualitative agreement was reached with experiments. Finally, in order to understand the atomic level changes that enable this increased amount of methane to dissolve in water, we have performed neutron scattering measurements along with EPSR (empirical potential structure refinement) fits to the data in order to solve the structure of the fluid mixture. These revealed a tendency towards maintaining the H-bond network present in water and homogeneous mixing. Despite the network staying similar to the one found in pure fluid water at milder pressures and temperatures (close to ambient conditions), the H-bonds seem more disordered and show a greater variability in their lengths.

Neste trabalho estudamos o efeito hidrofóbico no sistema benzenoágua. Nossa estratégia é avaliar as propriedades das ligações de hidrogênio entre as moléculas de água nas proximidades da molécula e benzeno. Utilizamos as ferramentas da mecânica quântica e o método de simulação computacional para este estudo. A análise estrutural e energética detalhada dos clusters benzenoágua mostra que a ligação de hidrogênio é mais forte quando na presença do benzeno. A investigação pelo método de simulação Monte Carlo corrobora estas conclusões e ainda fornece os efeitos da variação de tempeatura. Verificamos que o aumento da temperatura afeta todas as moléculas aumentando a desordem líquida, no entanto, constatamos a manutenção de uma estrutura de ligações de hidrogênio mais fortes as proximidades do benzeno. A interação entre duas moléculas de benzeno também foi analisada, mostrando que a interação benzenobenzeno é bem mais forte na presença da água. / The hydrophobic effect is studied for the benzene-water system. The properties of the hydrogen bond between the water molecules around the benzene is evaluated using both classical and quantum mechanical methods. Hydrophobic hydration analysis shows that the hydrogen bond interaction is stronger in the presence of benzene. This is verified both by ab initio quantum mechanical methods and classical Monte Carlo simulation. Temperature dependence is investigated. Although increasing temperature increases the disorder the hydrogen bonds between the water molecules are still stronger for those in the proximities of the benzene. Hydrophobic interaction is also investigated. It is seen that the benzene-benzene interaction is stronger in the water environment.