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 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.     

How ions affect the structure of water

We model ion solvation in water. We use the MB model of water, a simple two-dimensional statistical mechanical model in which waters are represented as Lennard-Jones disks having Gaussian hydrogen-bonding arms. We introduce a charge dipole into MB waters. We perform (NPT) Monte Carlo simulations to explore how water molecules are organized around ions and around nonpolar solutes in salt solutions. The model gives good qualitative agreement with experiments, including Jones-Dole viscosity B coefficients, Samoilov and Hirata ion hydration activation energies, ion solvation thermodynamics, and Setschenow coefficients for Hofmeister series ions, which describe the salt concentration dependence of the solubilities of hydrophobic solutes. The two main ideas captured here are (1) that charge densities govern the interactions of ions with water, and (2) that a balance of forces determines water structure: electrostatics (water's dipole interacting with ions) and hydrogen bonding (water interacting with neighboring waters). Small ions (kosmotropes) have high charge densities so they cause strong electrostatic ordering of nearby waters, breaking hydrogen bonds. In contrast, large ions (chaotropes) have low charge densities, and surrounding water molecules are largely hydrogen bonded.     

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.     

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.     

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.     

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.     

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).     

Hydration forces underlie the exclusion of salts and of neutral polar solutes from hydroxypropylcellulose

The distance dependence for the preferential exclusion of several salts and neutral solutes from hydroxypropyl cellulose (HPC) has been measured via the effect of these small molecules on the thermodynamic forces between HPC polymers in ordered arrays. The concentration of salts and neutral solutes decreases exponentially as the spacing between apposing nonpolar HPC surfaces decreases. For all solutes, the spatial decay lengths of this exclusion are remarkably similar to those observed between many macromolecules at close spacings where intermolecular forces have been ascribed to the energetics of water structuring. Exclusion magnitudes depend strongly on the nature and size of the particular salt or solute; for the three potassium salts studied, exclusion follows the anionic Hofmeister series. The change in the number of excess waters associated with HPC polymers is independent of solute concentration suggesting that the dominating interactions are between solutes and the hydrated polymer. These findings further confirm the importance of solvation interactions and reveal an unexpected unity of Hofmeister effects, preferential hydration, and hydration forces.     

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.     

The Nature of Aqueous Solutions: Insights into Multiple Facets of Chemistry and Biochemistry from Freezing‐Point Depressions

Contrary to current widely held beliefs, many concentrated aqueous solutions of electrolytes and nonelectrolytes behave ideally. For both, the same simple equation yields mole fractions of water that are equal to the theoretical activities of water. No empirical activity coefficients or ad hoc parameters are needed. Thermodynamic hydration numbers and the number of particles produced per mole of solute are found by searching freezing‐point depression measurements, as if asking the water, “How much available water solvent is left and how many solute particles are there?” The results answer questions currently under debate: Do solutes alter the nature of water outside their immediate surroundings? What is the number of ion pairs formed by various electrolytes and what affects extents of their formation? What are some factors that cause precipitation of proteins, latexes, and so forth from aqueous solutions upon addition of other solutes (Hofmeister series)? Which nonelectrolytes form aggregates in water and what are the implications? Why do different solutes affect viscosity differently? How do ion‐selective channels in cell membranes function at the molecular level?     

Watching the low-frequency motions in aqueous salt solutions: the terahertz vibrational signatures of hydrated ions

The details of ion hydration still raise fundamental questions relevant to a large variety of problems in chemistry and biology. The concept of water "structure breaking" and "structure making" by ions in aqueous solutions has been invoked to explain the Hofmeister series introduced over 100 years ago, which still provides the basis for the interpretation of experimental observations, in particular the stabilization/destabilization of biomolecules. Recent studies, using state-of-the-art experiments and molecular dynamics simulations, either challenge or support some key points of the structure maker/breaker concept, specifically regarding long-ranged ordering/disordering effects. Here, we report a systematic terahertz absorption spectroscopy and molecular dynamics simulation study of a series of aqueous solutions of divalent salts, which adds a new piece to the puzzle. The picture that emerges from the concentration dependence and assignment of the observed absorption features is one of a limited range of ion effects that is confined to the first solvation shell.     

The influence of Hofmeister series ions on hyaluronan swelling and viscosity

The dissolution of hyaluronan in water leads to its degradation, and as a result its molecular weight decreases. The degradation of hyaluronan is mainly influenced by temperature, solution composition, and also its pH. This study describes the influence of Hofmeister series ions on hyaluronan behaviour and hyaluronan film swelling by solutions of these ions. It was found that Hofmeister ions show lyotropic effects influencing the entanglement of hyaluronan coils and their expansion from solid polymer films into swollen gel state. The hydrophobic and hydrophilic interactions in the structure of hyaluronan macromolecules are represented by the mutual diffusion coefficient D(c), the mean mutual diffusion coefficient D(s), the expansion work of coil swelling RA(delta,s), the activation enthalpy of diffusion connected with swelling H(D,s) and kinematic viscosity of hyaluronan-ions solutions nu.     

Influence of salt ions on binding to molecularly imprinted polymers

Salt ions were found to have an influence on template binding to two model molecularly imprinted polymers (MIPs), targeted to penicillin G and propranolol, respectively, in water–acetonitrile mixtures. Water was detrimental to rebinding of penicillin G whereas propranolol bound in the entire water–acetonitrile range tested. In 100% aqueous solution, 3-M salt solutions augmented the binding of both templates. The effects followed the Hofmeister series with kosmotropic ions promoting the largest increase. Binding was mainly of a non-specific nature under these conditions. In acetonitrile containing low amounts of water, the specific binding to the MIPs increased with the addition of salts. Binding of penicillin G followed the Hofmeister series while an ion-exchange mechanism was observed for propranolol. The results suggest that hydration of kosmotropic ions reduces the water activity in water-poor media providing a stabilizing effect on water-sensitive MIP–template interactions. The effects were utilized to develop a procedure for molecularly imprinted solid-phase extraction (MISPE) of penicillin G from milk with a recovery of 87%.     

Hofmeister effects in surface tension of aqueous electrolyte solution

The surface tension of electrolyte solutions shows marked specific ion effects. We here show an important role for both ionic solvation energies and ionic dispersion potentials in determining this ion specific surface tension of salt solutions. The ion self-free energy changes when an ion moves from bulk solution into the interfacial region, with its decreasing water density profile. We will show that the solvation energies of different ions correlate very well with the surface tension of salt solutions. Inclusion of this distance-dependent self-free energy contribution brings qualitative agreement with experiments and the right Hofmeister series. This is so not only for surface tension changes but also for measured surface potentials. The inclusion of ionic dispersion interaction potentials further improves the agreement with experiments. We discuss how further progress in the theory of the surface tension of salts can be achieved.     

Ions at interfaces: the central role of hydration and hydrophobicity

It is increasingly being accepted that solvation properties of ions and interfaces (hydration of ions, hydrophobic or hydrophilic character of interfaces) play a fundamental role in ion-surface interaction in water. However, a fundamental understanding of the precise role of solvation in ionic specificity in colloidal systems is still missing, although important progress has been made over the last years. We present in this contribution experimental evidences (including also ions not usually included in specific ion studies) together with Molecular Dynamics (MD) simulations that highlight the importance of the hydration of ions and surfaces in order to understand the origin of ionic specificity. We first show that both surface polarity and ion hydration determine the sorting of ions according to their ability to induce specific effects (the so-called Hofmeister series). We extend these classical series by considering the addition of the inorganic anions IO₃⁻, BrO₃⁻ and ClO₃⁻, which present unusual properties as compared with the ions considered in classical Hofmeister series. We also consider big hydrophobic organic ions such as tetraphenylborate anion (Ph₄B⁻) and tetraphenylarsonium cation (Ph₄As⁺) that in the context of the Hofmeister series behave as super-chaotropes ions.     

The influence of ion binding and ion specific potentials on the double layer pressure between charged bilayers at low salt concentrations

Measurements of surface forces between double-chained cationic bilayers adsorbed onto molecularly smooth mica surfaces across different millimolar salt solutions have revealed a large degree of ion specificity [Pashley et al., J. Phys. Chem. 90, 1637 (1986)]. This has been interpreted in terms of highly specific anion binding to the adsorbed bilayers. We show here that inclusion in the double layer theory of nonspecific ion binding and ion specific nonelectrostatic potentials acting between ions and the two surfaces can account for the phenomenon. It also gives the right Hofmeister series for the double layer pressure.     

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.     

Why pH titration in protein solutions follows a Hofmeister series

Measurements of pH in single-phase cytochrome c suspensions are reported. The pH, as determined by a glass electrode, has a fixed value. With the addition of salt, the supposedly fixed pH changes strongly. The pH depends on salt type and concentration and follows a Hofmeister series. A theoretical interpretation is given that provides insights into such Hofmeister effects. These occur generally in protein solutions. While classical electrostatic models provide partial understanding of such trends in protein solutions, they fail to explain the observed ion specificity. Such models neglect electrodynamic fluctuation (dispersion) forces acting between ions and proteins. We use a Poisson-Boltzmann cell model that takes these ionic dispersion potentials between ions and proteins into account. The observed ion specificity can then be accounted for. Proteins act as buffers that display similar salt-dependent pH trends not previously explained.