Thermodynamics of non-electrolyte transfer between octanol and water

The apparent enthalpy, free energy and entropy of transfer from aqueous buffer (pH 7) to water-saturated octanol were determined for the aliphatic alcohols methanol to octanol using an isoperibol flow-calorimeter. For the higher homologues, a linear relationship between enthalpy and free energy change is found indicating an enthalpy-entropy compensation effect. The thermodynamics of transfer were rationalized in terms of the thermodynamics of solvation in the separate phases, including water itself as a solute. The role of water as a cosolvent in the octanol phase is discussed.Presented at the sixth Italian meeting on Calorimetry and Thermal Analysis (AICAT) held in Naples, December 4–7, 1984.     

Hydration patterns and salting effects in sodium chloride solution

The salting effects of 2M sodium chloride electrolyte are studied based on a series of model solutes with properties ranging from hydrophobic to hydrophilic. Generally, hydrophobic solutes will be salted out and hydrophilic solutes will be salted in by NaCl solution. The solvation free energy changes are highly correlated with Kirkwood-Buff integrals. The underlying mechanism resorts to the preferential binding of ions and water to solutes. Our results demonstrate that the salting effect not only depends on the salt's position in Hofmeister series, but also on the solutes' specifics. Taking the hydration free energies of solutes and ions as independent variables, a schematic diagram of salting effects is suggested. The resolved multifaceted salting effects rely on the sensitive balance of the tripartite interaction among solutes, ions, and water.     

Dispersion self-free energies and interaction free energies of finite-sized ions in salt solutions

The role for many-body dipolar (dispersion) potentials in ion-solvent and ion-solvent-interface interactions is explored. Such many-body potentials, accessible in principle from measured dielectric data, are necessary in accounting for Hofmeister specific ion effects. Dispersion self-energy is the quantum electrodynamic analogue of the Born electrostatic self-energy of an ion. We here describe calculations of dispersion self-free energies of four different anions (OH-, Cl-, Br-, and I-) that take finite ion size into account. Three different examples of self-free energy calculations are presented. These are the self-free energy of transfer of an ion to bulk solution, which influences solubility; the dispersion potential acting between one ion and an air-water interface (important for surface tension calculations); and the dispersion potential acting between two ions (relevant to activity coefficient calculations). To illustrate the importance of dispersion self-free energies, we compare the Born and dispersion contributions to the free energy of ion transfer from water to air (oil). We have also calculated the change in interfacial tension with added salt for air (oil)-water interfaces. A new model is used that includes dispersion potentials acting on the ions near the interface, image potentials, and ions of finite size that are allowed to spill over the solution-air interface. It is shown that interfacial free energies require a knowledge of solvent profiles at the interface.     

Do hydration forces play a role in thin film drainage and rupture observed in electrolyte solutions?

The mechanism that controls bubble coalescence in electrolyte solutions remains unresolved. The problem is difficult as sensitive dynamic thin film processes are critical. Here we discuss the relationship between film dynamics, specific-ion effects and the combining rules that codify electrolyte effects on bubble coalescence. The relationship with Hofmeister effects is explored, revealing that these very different manifestations of specific ion effects ultimately have the same origin, being the interfacial positioning of ions, which for the air–water interface correlates with the empirically derived α and β assignments used in the combining rules. Ion hydration is important as it strongly influences the interfacial positioning of ions and therefore ultimately bubble coalescence, however dynamic events determine if a collision results in coalescence and therefore we conclude that hydration forces play no role in bubble coalescence in electrolyte solutions.     

Surprising Hofmeister Effects on the Bending Vibration of Water

The Hofmeister series, which originally described the specific ion effects on the solubility of macromolecules in aqueous solutions, has been a long‐standing unsolved and exceptionally challenging mystery in chemistry. The complexity of specific ion effects has prevented a unified theory from emerging. Accumulating research has suggested that the interactions among ions, water and various solutes play roles. However, among these interactions, the binding between ions and solutes is receiving most of the attention, whereas the effects of ions on the hydrogen‐bond structure in liquid water have been deemed to be negligible. In this study, attenuated‐total‐reflectance Fourier transform infrared spectroscopy is used to study the infrared spectra of salt solutions. The results show that the red‐ and blue‐shifts of the water bending band are in excellent agreement with the characteristic Hofmeister series, which suggests that the ions’ effects on water structure might be the key role in the Hofmeister phenomenon.     

Thermodynamic origin of hofmeister ion effects

Quantitative interpretation and prediction of Hofmeister ion effects on protein processes, including folding and crystallization, have been elusive goals of a century of research. Here, a quantitative thermodynamic analysis, developed to treat noncoulombic interactions of solutes with biopolymer surface and recently extended to analyze the effects of Hofmeister salts on the surface tension of water, is applied to literature solubility data for small hydrocarbons and model peptides. This analysis allows us to obtain a minimum estimate of the hydration b1 (H2O A(-2)), of hydrocarbon surface and partition coefficients Kp, characterizing the distribution of salts and salt ions between this hydration water and bulk water. Assuming that Na+ and SO4(2-) ions of Na2SO4 (the salt giving the largest reduction in hydrocarbon solubility as well as the largest increase in surface tension) are fully excluded from the hydration water at hydrocarbon surface, we obtain the same b1 as for air-water surface (approximately 0.18 H2O A(-2)). Rank orders of cation and anion partition coefficients for nonpolar surface follow the Hofmeister series for protein processes, but are strongly offset for cations in the direction of exclusion (preferential hydration). By applying a coarse-grained decomposition of water accessible surface area (ASA) into nonpolar, polar amide, and other polar surface and the same hydration b1 to interpret peptide solubility increments, we determine salt partition coefficients for amide surface. These partition coefficients are separated into single-ion contributions based on the observation that both Cl- and Na+ (also K+) occupy neutral positions in the middle of the anion and cation Hofmeister series for protein folding. Independent of this assignment, we find that all cations investigated are strongly accumulated at amide surface while most anions are excluded. Cation and anion effects are independent and additive, allowing successful prediction of Hofmeister salt effects on micelle formation and other processes from structural information (ASA).     

Free energy of solvation of simple ions: molecular-dynamics study of solvation of Cl- and Na+ in the ice/water interface

Molecular-dynamics simulations of Cl(-) and Na(+) ions are performed to calculate ionic solvation free energies in both bulk simple point-charge/extended water and ice 1 h at several different temperatures, and at the basal ice 1 h/water interface. For the interface we calculate the free energy of "transfer" of the ions across the ice/water interface. For the ions in bulk water in the NPT ensemble at 298 K and 1 atm, results are found to be in good agreement with experiments, and with other simulation results. Simulations performed in the NVT ensemble are shown to give equivalent solvation free energies, and this ensemble is used for the interfacial simulations. Solvation free energies of Cl(-) and Na(+) ions in ice at 150 K are found to be approximately 30 and approximately 20 kcal mol(-1), respectively, less favorable than for water at room temperature. Near the melting point of the model the solvation of the ions in water is the same (within statistical error) as that measured at room temperature, and in the ice is equivalent and approximately 10 kcal mol(-1) less favorable than the liquid. The free energy of transfer for each ion across ice/water interface is calculated and is in good agreement with the bulk observations for the Cl(-) ion. However, for the model of Na(+) the long-range electrostatic contribution to the free energy was more negative in the ice than the liquid, in contrast with the results observed in the bulk calculations.     

Comparison of two simulation methods to compute solvation free energies and partition coefficients

The thermodynamic integration (TI) and expanded ensemble (EE) methods are used here to calculate the hydration free energy in water, the solvation free energy in 1‐octanol, and the octanol‐water partition coefficient for a six compounds of varying functionality using the optimized potentials for liquid simulations (OPLS) all‐atom (AA) force field parameters and atomic charges. Both methods use the molecular dynamics algorithm as a primary component of the simulation protocol, and both have found wide applications in fields such as the calculation of activity coefficients, phase behavior, and partition coefficients. Both methods result in solvation free energies and 1‐octanol/water partition coefficients with average absolute deviations (AAD) from experimental data to within 4 kJ/mol and 0.5 log units, respectively. Here, we find that in simulations the OPLS‐AA force field parameters (with fixed charges) can reproduce solvation free energies of solutes in 1‐octanol with AAD of about half that for the solute hydration free energies using a extended simple point charge (SPC/E) model of water. The computational efficiency of the two simulation methods are compared based on the time (in nanoseconds) required to obtain similar standard deviations in the solvation free energies and 1‐octanol/water partition coefficients. By this analysis, the EE method is found to be a factor of nine more efficient than the TI algorithm. For both methods, solvation free energy calculations in 1‐octanol consume roughly an order of magnitude more CPU hours than the hydration free energy calculations. © 2012 Wiley Periodicals, Inc.     

Hofmeister anionic effects on hydration electric fields around water and peptide

Specific ion effects on water dynamics and local solvation structure around a peptide are important in understanding the Hofmeister series of ions and their effects on protein stability in aqueous solution. Water dynamics is essentially governed by local hydrogen-bonding interactions with surrounding water molecules producing hydration electric field on each water molecule. Here, we show that the hydration electric field on the OD bond of HOD molecule in water can be directly estimated by measuring its OD stretch infrared (IR) radiation frequency shift upon increasing ion concentration. For a variety of electrolyte solutions containing Hofmeister anions, we measured the OD stretch IR bands and estimated the hydration electric field on the OD bond to be about a hundred MV∕cm with standard deviation of tens of MV∕cm. As anion concentration increases from 1 to 6 M, the hydration electric field on the OD bond decreases by about 10%, indicating that the local H-bond network is partially broken by dissolved ions. However, the measured hydration electric fields on the OD bond and its fluctuation amplitudes for varying anions are rather independent on whether the anion is a kosmotrope or a chaotrope. To further examine the Hofmeister effects on H-bond solvation structure around a peptide bond, we examined the amide I' and II' mode frequencies of N-methylacetamide in various electrolyte D(2)O solutions. It is found that the two amide vibrational frequencies are not affected by ions, indicating that the H-bond solvation structure in the vicinity of a peptide remains the same irrespective of the concentration and character of ions. The present experimental results suggest that the Hofmeister anionic effects are not caused by direct electrostatic interactions of ions with peptide bond or water molecules in its first solvation shell. Furthermore, even though the H-bond network of water is affected by ions, thus induced change of local hydration electric field on the OD bond of HOD is not in good correlation with the well-known Hofmeister series. We anticipate that the present experimental results provide an important clue about the Hofmeister effect on protein structure and present a discussion on possible alternative mechanisms.     

Interactions of halophenols with aqueous micellar systems

The interaction of a series of halophenols with sodium dodecyl sulphate and hexadecyltrimethylammonium bromide micelles was studied by different techniques (high-performance liquid chromatography, apparent acidity constant, spectral shift). The contributions of the halogens to the free energy of transfer from water to micelles are calculted. Correlations between the free energy of transfer for water/micellar solutions and for the classical octanol/water system are good. The application of micellar systems in chromatography and acid-base titrations is verified.     

Transferability of fragmental contributions to the octanol/water partition coefficient: an NDDO-based MST study

This study examines the transferability of fragmental contributions to the octanol/water partition coefficient. As a previous step, we report the parameterization of the AM1 and PM3 versions of the MST model for n-octanol. The final AM1 and PM3 MST models reproduce the experimental free energy of solvation and the octanol/water partition coefficient (log P(ow)) with a root-mean-square deviation of around 0.7 kcal/mol and 0.5 (in units of log P), respectively. Based on this parameterization, an NNDO-based procedure is presented to dissect the free energy of transfer between octanol and water in contributions directly associated with specific atoms or functional groups. The application of this procedure to a set of representative molecular systems illustrates the dependence of the log P(ow) fragmental contribution due to electronic, hydrogen bonding, and steric effects, which cannot be easily accounted for in simple additive-based empirical schemes. The results point out the potential use of theoretical methods to refine the fragmental contributions in empirical methods.     

Hofmeister离子对水溶液中热响应聚合物的局域环境的影响

The Hofmeister ion effect is a very interesting but elusive phenomenon, the importance of which is revealed in self-assembly, ion recognition, and protein folding regulation. With an increasing number of studies suggesting that interactions between ions and solutes play a role in the Hofmeister ion effect, the nature of the Hofmeister phenomenon becomes more debatable. Yet, it is not clear whether the Hofmeister ion effect is a local effect or bulk effect that can reach beyond many hydration shells, where specific interactions between ions and solutes play key roles. In order to further explore this, we applied proton nuclear magnetic resonance (¹H-NMR) spectroscopy to study the effects of specific ions on the local environment around N, N-dimethylpropionamide (NDA) and N-isopropylisobutyramide (NPA), which are the model compounds for poly(2-ethyl-2-oxazoline) and poly(N-isopropylacrylamide), respectively. These polymers are important bio-engineering materials that possess thermoresponsive properties and are also subject to specific ion effects. By correlating the changes in chemical shifts of the two methyl groups on either side of the amide bond, it was found that the Hofmeister ion effects on NPA were more anisotropic than on NDA, and that the cationic effects were more anisotropic than the anionic effects on NPA. These results indicated that the effects of specific ions were almost identical for all methyl groups of NDA. On the other hand, NPA is a larger molecule; thus, not all of its methyl groups were subjected to the specific ion effects to the same extent. The calculation of the electrostatic potential surfaces of NDA and NPA suggested that these observations on the Hofmeister ion effects might be due to steric hindrance, and that the observations on the cationic effects might be due to the interactions between cations and NPA being stronger than the interactions between anions and NPA. This would explain why the highly charged cations caused a significant anisotropicity. Additionally, we found that the chemical shift of the water protons (Δδ_H2O) of conventional kosmotropic anions was larger than zero, which suggested a stronger HB and more charge transfer between water and these anions. The Δδ_H2O of conventional chaotropic anions was less than zero. Despite the different solutes, the results were indifferent in both NDA and NPA solutions. Surprisingly, the Δδ_H2O of Cl^- at concentrations lower than 1 mol∙L^-1 was zero, thus becoming the benchmark between chaotropes and kosmotropes. These results suggested a quantitative measurement of kosmotropicity/chaotropicity, where the anion would be kosmotropic if its Δδ_H2O were higher than that of Cl^- and chaotropic for the opposing condition. Moreover, the results showed that the effects of the cations on the water structure were minimal, which was consistent with minimal charge transfer between the cations and water. The overall results of this study suggest that the Hofmeister ion effect is a global effect, while local interactions of ions with solutes also play a key role.     

On the mechanism of the hofmeister effect

Vibrational sum frequency spectroscopy was used to probe fatty amine monolayers spread on various electrolyte solutions. The spectra revealed ion specific changes in both monolayer ordering and water structure with the former following the Hofmeister series. Separate measurements of the surface potential as a function of ion tracked closely to changes in alkyl chain structure, but less closely to changes in water structure. The disruption of the monolayer ordering could be ascribed to the relative ability of the ions to penetrate past the hydrophilic surface of the monolayer's headgroups and into the more hydrophobic portion of the thin film. The corresponding trends observed in the surface water structure showed significant deviations from the Hofmeister series, leading to the conclusion that the changes in surface water structure, often credited with being the origin of Hofmeister effects, are probably not of primary importance. On the other hand, dispersion forces almost certainly play a large role in the order of the Hofmeister series.     

Direct calculation of 1-octanol-water partition coefficients from adaptive biasing force molecular dynamics simulations

The 1-octanol-water partition coefficient log K(ow) of a solute is a key parameter used in the prediction of a wide variety of complex phenomena such as drug availability and bioaccumulation potential of trace contaminants. In this work, adaptive biasing force molecular dynamics simulations are used to determine absolute free energies of hydration, solvation, and 1-octanol-water partition coefficients for n-alkanes from methane to octane. Two approaches are evaluated; the direct transfer of the solute from 1-octanol to water phase, and separate transfers of the solute from the water or 1-octanol phase to vacuum, with both methods yielding statistically indistinguishable results. Calculations performed with the TIP4P and SPC∕E water models and the TraPPE united-atom force field for n-alkanes show that the choice of water model has a negligible effect on predicted free energies of transfer and partition coefficients for n-alkanes. A comparison of calculations using wet and dry octanol phases shows that the predictions for log K(ow) using wet octanol are 0.2-0.4 log units lower than for dry octanol, although this is within the statistical uncertainty of the calculation.     

Hofmeister effects at low salt concentration due to surface charge transfer

We present a theoretical comparison of the surface forces between two graphite-like surfaces at salt concentrations below 10 mM with surfaces charged by various mechanisms. Surface forces include a surface charging or chemisorption contribution to the total free energy. Surfaces are charged by charge regulation (H⁺ binding), site competition (H⁺ and cation binding) and redox charging with electrodes coupled to a countercell. Constant surface charge is also considered. Surface parameters are calibrated to give the same potential when isolated. Nonelectrostatic physisorption energies of the potential determining ions provide a specific and significant contribution to the charging energy. Consequently ion specificity is found in the surface forces at concentrations of 1–10 mM, which is not observed under constant charge conditions. The force between redox electrodes continues to show Hofmeister effects at 0.01 mM. We refer to this low concentration Hofmeister effect as “Hofmeister charging”, and suggest that the more common high concentration ion specific effects may be known as “Hofmeister screening”. Hofmeister series are considered over LiCl, NaCl, KCl and NaNO₃, NaClO₄, NaSCN with the cations (or H⁺) being the potential determining ions. A K⁺ anomaly is attributed to the small size of the weakly hydrated chaotropic K⁺ ion, with Li⁺ and Na⁺ explicitly modelled as strongly hydrated cosmotropes.     

Measurement of real free energies of transfer of individual ions from water to other solvents with the jet cell

Resolution of the activities of solutions of electrolytes into the individual ionic contributions cannot be carried out rigorously and requires the introduction of extrathermodynamic assumptions which have inherent uncertainties. The most commonly used approaches are basically similar in that they are based on the assumed solvent independence of the difference in the enthalpy or Gibbs energy of transfer of pairs of model solutes, e.g., tetraphenylarsonium and tetraphenylborate ions, or ferricinium ion and ferrocene. In this work we follow an alternative approach pioneered by Parsons involving measurement in the jet (Kenrick) cell of outer-potential differences between solutions of the same electrolyte in two solvents. These potential differences provide the real free energies of transfer of individual ions which, in turn, differ from the usual Gibbs energies of transfer by the work required to transfer the ion through the dipolar layers at the two solvent-gas interfaces. One objective of this work was to improve the reliability of real free energy of transfer measurements, which are experimentally demanding, to within ca. ±0.5 kJ-mol^–1 in order to match typical uncertainties in Gibbs transfer energies of electrolytes. This goal was met, in most instances, by careful evaluation of experimental parameters (particularly jet pressure). A major improvement over previous measurements was made by adding a supporting electrolyte which allowed stable potentials to be obtained at test electrolyte concentrations as low as 10^–4M. Real free energy changes are reported for the transfer of silver ion from water to methanol, ethanol, acetonitrile, propylene carbonate and dimethyl sulfoxide, as well as for the transfer of chloride ion from water to methanol and ethanol. Reliable data of this kind may lead to improved understanding of either the properties of the surfaces of solvents or the interactions of model solutes with solvents, depending on which of the two fields develops most.     

Solubility of naproxen in several organic solvents at different temperatures

By using the van’t Hoff and Gibbs equations the thermodynamic functions Gibbs free energy, enthalpy, and entropy of solution, were evaluated from solubility data of naproxen (NAP) determined at several temperatures in octanol, isopropyl myristate, chloroform, and cyclohexane, as pure solvents. The water-saturated organic solvents also were studied except cyclohexane. The excess free energy and the activity coefficients of the solutes, and the mixing and solvation thermodynamic quantities were also determined. The NAP solubilities were higher in chloroform and octanol with respect to those obtained in cyclohexane. In addition, by using literature values for NAP aqueous solubility, the thermodynamic functions relative to transfer of this drug from water to organic solvents were also estimated.     

A study of salt effects on the complexation between β-cyclodextrins and bile salts based on the Hofmeister series

The Hofmeister series is the ranking of ions according to their ability to strengthen (kosmotropic ions) or weaken (chaotropic ions) hydrophobic interactions. Such ions are therefore expected to affect the strength of cyclodextrin (CD) inclusion complexes and may thereby affect the release of CD bound drug molecules. The influence of Hofmeister ions on the binding constants of complexes between CDs (β-CD and hydroxypropylated β-CD) and bile salts (glycocholate and glycochenodeoxycholate) were examined by isothermal titration calorimetry. The chaotropic anions tended to weaken these inclusion complexes. Conversely, kosmotropic ions increased the binding strength and this effect scaled with the buried hydrophobic surface area. Both effects are relatively weak at physiological ion concentrations and may be neglected for most pharmaceutical purposes.     

Ions interacting in solution: Moving from intrinsic to collective properties

A crucial determinant of Hofmeister effects is the direct interaction of ions in solution with the charged groups on the surface of larger particles. Understanding ion–ion interactions in solution is therefore a necessary first step to explaining Hofmeister effects. Here, we advocate an approach to modeling these types of properties where state of the art Ab Initio Molecular Dynamics (AIMD) simulation of ions in solution is used to establish benchmark values for the intrinsic properties of ions in solution such as solvation structures and ion–ion Potentials of Mean Force (PMFs). This information can then be combined with, or used to parametrize and improve, reduced models, which use approximations such as the continuum solvent model (CSM). These reduced models can then be used to calculate collective and concentration dependent properties of electrolyte solution and so make accurate predictions about complex systems of relevance for direct applications. We provide an example of this approach using AIMD calculations of the sodium chloride PMF to calculate osmotic coefficients of all 20 alkali halide electrolytes.