Possible origin of the inverse and direct Hofmeister series for lysozyme at low and high salt concentrations

Protein solubility studies below the isoelectric point exhibit a direct Hofmeister series at high salt concentrations and an inverse Hofmeister series at low salt concentrations. The efficiencies of different anions measured by salt concentrations needed to effect precipitation at fixed cations are the usual Hofmeister series (Cl(-) > NO(3)(-) > Br(-) > ClO(4)(-) > I(-) > SCN(-)). The sequence is reversed at low concentrations. This has been known for over a century. Reversal of the Hofmeister series is not peculiar to proteins. Its origin poses a key test for any theoretical model. Such specific ion effects in the cloud points of lysozyme suspensions have recently been revisited. Here, a model for lysozymes is considered that takes into account forces acting on ions that are missing from classical theory. It is shown that both direct and reverse Hofmeister effects can be predicted quantitatively. The attractive/repulsive force between two protein molecules was calculated. To do this, a modification of Poisson-Boltzmann theory is used that accounts for the effects of ion polarizabilities and ion sizes obtained from ab initio calculations. At low salt concentrations, the adsorption of the more polarizable anions is enhanced by ion-surface dispersion interactions. The increased adsorption screens the protein surface charge, thus reducing the surface forces to give an inverse Hofmeister series. At high concentrations, enhanced adsorption of the more polarizable counterions (anions) leads to an effective reversal in surface charge. Consequently, an increase in co-ion (cations) adsorption occurs, resulting in an increase in surface forces. It will be demonstrated that among the different contributions determining the predicted specific ion effect the entropic term due to anions is the main responsible for the Hofmeister sequence at low salt concentrations. Conversely, the entropic term due to cations determines the Hofmeister sequence at high salt concentrations. This behavior is a remarkable example of the charge-reversal phenomenon.     

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.     

Hofmeister series: the hydrolytic activity of Aspergillus niger lipase depends on specific anion effects

The specific activity of lipase A (Aspergillus niger) toward the hydrolysis of p-nitrophenyl acetate (p-NPA) is shown to increase as a result of sodium salt addition according to specific ion effects of the Hofmeister series. This shows explicitly that the Hofmeister effect is due to the different specific interactions between anions and the enzymatic surface.     

The electrostatic origins of specific ion effects: quantifying the Hofmeister series for anions

Life as we know it is dependent upon water, or more specifically salty water. Without dissolved ions, the interactions between biological molecules are insufficiently complex to support life. This complexity is intimately tied to the variation in properties induced by the presence of different ions. These specific ion effects, widely known as Hofmeister effects, have been known for more than 100 years. They are ubiquitous throughout the chemical, biological and physical sciences. The origin of these effects and their relative strengths is still hotly debated. Here we reconsider the origins of specific ion effects through the lens of Coulomb interactions and establish a foundation for anion effects in aqueous and non-aqueous environments. We show that, for anions, the Hofmeister series can be explained and quantified by consideration of site-specific electrostatic interactions. This can simply be approximated by the radial charge density of the anion, which we have calculated for commonly reported ions. This broadly quantifies previously unpredictable specific ion effects, including those known to influence solution properties, virus activities and reaction rates. Furthermore, in non-aqueous solvents, the relative magnitude of the anion series is dependent on the Lewis acidity of the solvent, as measured by the Gutmann Acceptor Number. Analogous SIEs for cations bear limited correlation with their radial charge density, highlighting a fundamental asymmetry in the origins of specific ion effects for anions and cations, due to competing non-Coulombic phenomena.

Analysis of ions’ radial charge densities reveals they correlate with many specific ion effects, and provides a new basis to explain and quantify the 130-year-old Hofmeister series for anions.     

Influence of the Hofmeister series of anions on the molecular organization of positively ionized monolayers of a viologen derivative

The effects of the Hofmeister series of ions are ubiquitous in chemistry and biology. In this paper specific ion effects on the surface behavior of a viologen dication, namely 1,1(')-dioctadecyl-4,4(')-bipyridilium, are shown. Surface pressure and surface potential vs area isotherms were obtained on aqueous subphases containing potassium salts with several representative counterions in the Hofmeister series (C6H5O3-7, SO2 -4, HPO2-4, Cl-, Br-, NO-3, I-, and ClO-4). The parameters obtained from the compression isotherms (area per molecule, phase transitions, Young modulus, initial surface potential, and variation of the surface potential upon compression) are dependent on the nature of the counterion, indicating ion specificity. Aqueous subphases containing C6H5O3-7, SO2-4, and HPO2-4 anions yield more expanded viologen monolayers and these anions do not effectively penetrate into the monolayer. Brewster angle microscopy was used to map the different phases of the viologen monolayers at the air-water interface. The Langmuir films were also characterized by UV-vis spectroscopy, with quantitative analysis of the reflection spectra supporting an organizational model in which the viologen chromophore undergoes a gradual transition to a more vertical position with respect to the water surface upon compression. A comparison of the tilt angles of the viologen on the different subphases indicates that anions that can more easily penetrate in the monolayer permit the viologen moieties to adopt a slightly more vertical position with respect to the water surface.     

Ion specific surface forces between membrane surfaces

Entities such as ion distributions and forces between lipid membranes depend on effects due to the intervening salt solution that have not been recognized previously. These specific ion or Hofmeister effects influence membrane fusion. A typical illustrative example is this: measurements of forces between double-chained cationic bilayers adsorbed onto molecularly smooth mica surfaces across different 0.6-2 mM salt solutions have revealed a large degree of ion specificity [Pashley et al. J. Phys. Chem. 1986, 90, 1637]. This has been interpreted in terms of very specific anion "binding" to the adsorbed bilayers, as it would too for micelles and other self-assembled systems. However, we show here that inclusion of nonelectrostatic (NES) or ionic dispersion potentials acting between ions and the two surfaces explains such "ion binding". The observed Hofmeister sequence for the calculated pressure without any direct ion binding is given correctly. This demonstrates the importance of a source of ion specificity that has been ignored. It is due to ionic physisorption caused by attractive NES ionic dispersion potentials. There appear to be some far reaching consequences for interpretations of membrane intermolecular interactions in salt solutions.     

Interactions of Na-salts and 1-propanol in 1-propanol-Na-Salt-H2O systems: toward an understanding the Hofmeister series (IV)

The excess chemical potential of 1-propanol (1P), muE1P, was evaluated in ternary 1P-Na-salt(S)-H2O at 25 degrees C. The counter anions of the Na-salts studied are SO42-, F-, Cl-, I-, and ClO4-. The effect of the anion on muE1P follows the Hofmeister ranking, in that the more kosmotropic ions make the muE1P value more positive. We then evaluate the effect of the Na-salt (S) on muE1P, the 1P-S interaction in terms of excess chemical potential, at a semi-infinite dilution. The results indicate that the 1P-S interaction in terms of excess chemical potential is unfavorable (repulsive) for all of the ions studied. The degree of repulsive interaction decreases in the order of the Hofmeister ranking from the kosmotropic to the chaotropic end. Namely, salting-out samples make the excess part of the chemical potential of 1P more unfavorable, while the salting-in counterparts make it less unfavorable. From earlier calorimetric studies on the same ternary systems, the enthalpic 1P-S interaction function, HE 1P-S , was calculated. Hence, the entropy analogue, S1P-S , was also obtained, and a detailed thermodynamic signature of 1P-S interactions became available. This revealed that both HE 1P-S and SE 1P-S decrease from the kosmotropic ion to the middle of the ranking (Cl-), whereupon they turn to increase toward the chaotropic end. Hence, the build up of unfavorable 1P-S interactions in Hofmeister salts (signified by muE1P) relies on a pronounced enthalpy-entropy compensation, which must be accounted for in attempts to understand the molecular mechanisms underpinning Hofmeister effects.     

Quantification of specific anion binding to non-ionic Triton X-100 micelles

Anion binding to nonionic micelles was quantified by self-diffusion. Four anions were probed by multinuclear PGSTE NMR measurements in a Triton X-100 micellar aqueous solution. The salt concentration used was sufficiently low to avoid any micellar growth affecting surface curvature. The micellar aggregates that provide a model surface are uncharged with hydrophilic headgroups so that electrostatic ion surface interactions play little or no role in prescribing specific anion binding. Anionic affinity to the micellar surface followed a Hofmeister series, (CH(3))(2)AsO(2)(-) ? CH(3)COO(-) > H(2)PO(4)(-) > F(-). The observed ion specificity is rationalized by calling into play the nonelectrostatic interactions occurring between the anions and the micellar surface.     

Reversed Hofmeister series—The rule rather than the exception

Over recent years, the supposedly universal Hofmeister series has been replaced by a diverse spectrum of direct, partially altered and reversed series. This review aims to provide a detailed understanding of the full spectrum by combining results from molecular dynamics simulations, Poisson–Boltzmann theory and AFM experiments. Primary insight into the origin of the Hofmeister series and its reversal is gained from simulation-derived ion–surface interaction potentials at surfaces containing non-polar, polar and charged functional groups for halide anions and alkali cations. In a second step, the detailed microscopic interactions of ions, water and functional surface groups are incorporated into Poisson–Boltzmann theory. This allows us to quantify ion-specific binding affinities to surface groups of varying polarity and charge, and to provide a connection to the experimentally measured long-ranged electrostatic forces that stabilize colloids, proteins and other particles against precipitation. Based on the stabilizing efficiency, the direct Hofmeister series is obtained for negatively charged hydrophobic surfaces. Hofmeister series reversal is induced by changing the sign of the surface charge from negative to positive, by changing the nature of the functional surface groups from hydrophobic to hydrophilic, by increasing the salt concentration, or by changing the pH. The resulting diverse spectrum reflects that alterations of Hofmeister series are the rule rather than the exception and originate from the variation of ion-surface interactions upon changing surface properties.     

Hofmeister effects on the colloidal stability of an IgG-coated polystyrene latex

The effect of various ions related to the Hofmeister series (HS) on different properties of a cationic latex covered with a protein (IgG) is analyzed in this study. NaNO3, NH4NO3, and Ca(NO3)2 were used to compare the specificity of the cations, and NaCl, NaSCN, NaNO3, and Na2SO4, to compare the specificity of the anions. Two pH values, 4 and 10, were chosen to analyze the behavior of these ions acting as counter- and co-ions. At pH 4, the total surface charge is positive, whereas at pH 10 it is negative. Three different phenomena have been studied in the presence of these Hofmeister ions: (1) colloidal aggregation, (2) electrophoretic mobility, and (3) colloidal restabilization. The specific effect of the ions was clearly observed in all experiments, obtaining ion sequences ordered according to their specificity. The most important parameter for ion ordering was the sign of the charge of the colloidal particle. Positively charged particles displayed an ion order opposite that observed for negatively charged surfaces. Another influential factor was the hydrophobic/hydrophilic character of the particle surface. IgG-latex particle surfaces at pH 10 were more hydrophilic than those at pH 4. The SCN- ion had a peculiar specific effect on the phenomena studied (1)-(3) at pH 10. With respect to the restabilization studies at high ionic strengths, new interesting results were obtained. Whereas it is commonly known that cations may provoke colloidal restabilization in negative particles when they act as counterions, our experiments demonstrated that such restabilization is also possible with positively charged particles. Likewise, restabilization of negative surfaces induced by the specific effect of chaotropic anions (acting as co-ions) was also observed.     

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.     

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).     

Molecular hydrophobic attraction and ion-specific effects studied by molecular dynamics

Much is written about "hydrophobic forces" that act between solvated molecules and nonpolar interfaces, but it is not always clear what causes these forces and whether they should be labeled as hydrophobic. Hydrophobic effects roughly fall in two classes, those that are influenced by the addition of salt and those that are not. Bubble adsorption and cavitation effects plague experiments and simulations of interacting extended hydrophobic surfaces and lead to a strong, almost irreversible attraction that has little or no dependence on salt type and concentration. In this paper, we are concerned with hydrophobic interactions between single molecules and extended surfaces and try to elucidate the relation to electrostatic and ion-specific effects. For these nanoscopic hydrophobic forces, bubbles and cavitation effects play only a minor role and even if present cause no equilibration problems. In specific, we study the forced desorption of peptides from nonpolar interfaces by means of molecular dynamics simulations and determine the adsorption potential of mean force. The simulation results for peptides compare well with corresponding AFM experiments. An analysis of the various contributions to the total peptide-surface interactions shows that structural effects of water as well as van der Waals interactions between surface and peptide are important. Hofmeister ion effects are studied by separately determining the effective interaction of various ions with hydrophobic surfaces. An extension of the Poisson-Boltzmann equation that includes the ion-specific potential of mean force yields surface potentials, interfacial tensions, and effective interactions between hydrophobic surfaces. There, we also analyze the energetic contributions to the potential of mean force and find that the most important factor determining ion-specific adsorption at hydrophobic surfaces can best be described as surface-modified ion hydration.     

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.     

Anion Effects on Sodium Ion and Acid Molecule Adduction to Protein Ions in Electrospray Ionization Mass Spectrometry

Gaseous protein–metal ion and protein–molecule complexes can be readily formed by electrospray ionization (ESI) from aqueous solutions containing proteins and millimolar concentrations of sodium salts of various anions. The extent of sodium and acid molecule adduction to multiply charged protein ions is inversely related and depends strongly on the proton affinity (PA) of the anion, with extensive sodium adduction occurring for anions with PA values greater than ~300 kcal·mol^–1 and extensive acid molecule adduction occurring for anions with PA values less than 315 kcal·mol^–1. The role of the anion on the extent of sodium and acid molecule adduction does not directly follow the Hofmeister series, suggesting that direct protein–ion interactions may not play a significant role in the observed effect of anions on protein structure in solution. These results indicate that salts with anions that have low PA values may be useful solution-phase additives to minimize nonspecific metal ion adduction in ESI experiments designed to identify specific protein-metal ion interactions.     

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.     

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.     

The inevitable accumulation of large ions and neutral molecules near hydrophobic surfaces and small ions near hydrophilic ones

The present contribution offers a unified explanation to three central phenomena in physical chemistry of interfaces in contact with aqueous solution: (1) Accumulation of large anions at the air/water interface. (2) Accumulation of neutral gas molecules near hydrophobic surfaces and the resulting hydrophobic interaction between two such surfaces, and (3) The Hofmeister effect, namely, the enhanced propensity of small ions to hydrophilic surfaces and large ions to hydrophobic surfaces. The common thread linking these phenomena is the free energy balance between ion or molecule hydration in solution and the cost of localizing these objects at the water-surface interface. Comparing the results of an abstract lattice-gas model to force spectroscopy data collected by AFM we reveal the underlying principles and demonstrate their universality.     

Rotational dynamics of thiocyanate ions in highly concentrated aqueous solutions

The thiocyanate (SCN(-)) anion is known as one of the best denaturants, which is also capable of breaking the hydrogen-bond network of water and destabilizing native structures of proteins. Despite prolonged efforts to understand the underlying mechanism of such Hofmeister effects, detailed dynamics of the ions in a highly concentrated solution have not been fully elucidated yet. Here, we used a dispersive IR pump-probe spectroscopic method to study the dependence of vibrational lifetimes and rotational relaxation times of thiocyanate ions on KSCN concentration in D(2)O. The nitrile stretch mode is used as a vibrational probe for dispersed IR pump-probe and FTIR measurements. To avoid possible self-attenuation of the IR pump-probe signal by highly concentrated SCN(-) ions, we added a small amount of (13)C-isotope-labeled thiocyanate ions (S(13)CN(-)) and focused on the excited-state absorption contribution to the IR pump-probe signal of the (13)C-isotope-labeled nitrile stretch mode. Quite unexpectedly, the vibrational lifetime of S(13)CN(-) ions is independent of the total KSCN concentration in the range from 0.46 m (molality) to 11.8 m while the rotational relaxation time of S(13)CN(-) ions is linearly dependent on the total KSCN concentration. By combining the present experimental findings with the fact that the dissolved ions of KSCN salt have a strong tendency to form a large ion cluster in a highly concentrated aqueous solution, we believe that the ion clusters consisting of potassium and thiocyanate ion pairs in D(2)O behave like ionic liquids and the ions inside ion clusters are weakly bound by electrostatic Coulombic interactions. The ability of SCN(-) ions to form ion clusters in aqueous protein solutions seems to be a key to understand the Hofmeister ion effect. We anticipate that the present experimental results provide a clue for further elucidating the underlying mechanism of the Hofmeister ion effects on protein stability in the future.     

Novel Applications of Non Hofmeister Ion Specificity in Bubble Interactions

The ion specificity of bubble-bubble interactions in water remains unexplained. Whatever their valence all ion pairs either completely inhibit bubble coalescence or have no effect whatever. The phenomenon appears unrelated to Hofmeister specificity. Salts which inhibit coalescence enable the formation of a high density bubble column evaporator (BCE). If hot gas bubbles are injected into the bubble column evaporator at a significantly higher temperature than the water, the hot bubble surfaces can be used to produce thermal effects in dissolved and dispersed solutes. These two properties can be exploited for a wide range of applications. Among these, high temperature aqueous reactions catalyzed at low solution temperatures, measurement of enthalpies of vaporization of concentrated salt solutions, wastewater treatments by sterilization and de-watering and desalination are a few.