The Hofmeister effect and the behaviour of water at interfaces

Starting from known properties of non-specific salt effects on the surface tension at an air-water interface, we propose the first general, detailed qualitative molecular mechanism for the origins of ion-specific (Hofmeister) effects on the surface potential difference at an air-water interface; this mechanism suggests a simple model for the behaviour of water at all interfaces (including water-solute interfaces), regardless of whether the non-aqueous component is neutral or charged, polar or non-polar. Specifically, water near an isolated interface is conceptually divided into three layers, each layer being I water-molecule thick. We propose that the solute determines the behaviour of the adjacent first interfacial water layer (I1); that the bulk solution determines the behaviour of the third interfacial water layer (I3), and that both I1 and I3 compete for hydrogen-bonding interactions with the intervening water layer (I2), which can be thought of as a transition layer. The model requires that a polar kosmotrope (polar water-structure maker) interact with I1 more strongly than would bulk water in its place; that a chaotrope (water-structure breaker) interact with I1 somewhat less strongly than would bulk water in its place; and that a non-polar kosmotrope (non-polar water-structure maker) interact with I1 much less strongly than would bulk water in its place. We introduce two simple new postulates to describe the behaviour of I1 water molecules in aqueous solution. The first, the 'relative competition' postulate, states that an I1 water molecule, in maximizing its free energy (--delta G), will favour those of its highly directional polar (hydrogen-bonding) interactions with its immediate neighbours for which the maximum pairwise enthalpy of interaction (--delta H) is greatest; that is, it will favour the strongest interactions. We describe such behaviour as 'compliant', since an I1 water molecule will continually adjust its position to maximize these strong interactions. Its behaviour towards its remaining immediate neighbours, with whom it interacts relatively weakly (but still favourably), we describe as 'recalcitrant', since it will be unable to adjust its position to maximize simultaneously these interactions.(ABSTRACT TRUNCATED AT 400 WORDS)     

Wilhelm Hofmeister

Ohne Zusammenfassung     

Water absorbency by wool fibers: Hofmeister effect

Wool is a complex material, composed of cuticle and epicuticle cells, surrounded by a cell membrane complex. Wool fibers absorb moisture from air, and, once immersed in water, they take up considerable amounts of liquid. The water absorbency parameter can be determined from weight gain, according to a standard method, and used to quantify this phenomenon. In this paper we report a study on the water absorbency (or retention) of untreated wool fibers in the presence of aqueous 1 M salt solutions at 29 degrees C and a relative humidity of either 33% or 56%. The effect of anions was determined by selecting a wide range of different sodium salts, while the effect of cations was checked through some chlorides and nitrates. Our results show a significant specific ion and ion pair "Hofmeister" effects, that change the amount of water absorbed by the fibers. To understand this phenomenon, the water absorbency parameter (A(w)) is compared to different physicochemical parameters such as the lyotropic number, free energy of hydration of ions, molar surface tension increment, polarizability, refractive index increment, and molar refractivity. The data indicate that this Hofmeister phenomenon is controlled by dispersion forces that depend on the polarizability of ionic species, their adsorption frequencies, the solvent, and the substrate. These dispersion forces dominate the behavior in concentrated solutions. They are in accord with new developing theories of solutions and molecular interactions in colloidal systems that account for Hofmeister effects.     

The Hofmeister effect on amyloid formation using yeast prion protein

A variety of proteins are capable of converting from their soluble forms into highly ordered fibrous cross‐β aggregates (amyloids). This conversion is associated with certain pathological conditions in mammals, such as Alzheimer disease, and provides a basis for the infectious or hereditary protein isoforms (prions), causing neurodegenerative disorders in mammals and controlling heritable phenotypes in yeast. The N‐proximal region of the yeast prion protein Sup35 (Sup35NM) is frequently used as a model system for amyloid conversion studies in vitro. Traditionally, amyloids are recognized by their ability to bind Congo Red dye specific to β‐sheet rich structures. However, methods for quantifying amyloid fibril formation thus far were based on measurements linking Congo Red absorbance to concentration of insulin fibrils and may not be directly applicable to other amyloid‐forming proteins. Here, we present a corrected formula for measuring amyloid formation of Sup35NM by Congo Red assay. By utilizing this corrected procedure, we explore the effect of different sodium salts on the lag time and maximum rate of amyloid formation by Sup35NM. We find that increased kosmotropicity promotes amyloid polymerization in accordance with the Hofmeister series. In contrast, chaotropes inhibit polymerization, with the strength of inhibition correlating with the B‐viscosity coefficient of the Jones‐Dole equation, an increasingly accepted measure for the quantification of the Hofmeister series.     

Hofmeister effect in confined spaces: halogen ions and single molecule detection

Despite extensive research in the nanopore-sensing field, there is a paucity of experimental studies that investigate specific ion effects in confined spaces, such as in nanopores. Here, the effect of halogen anions on a simple bimolecular complexation reaction between monodisperse poly(ethylene glycol) (PEG) and α-hemolysin nanoscale pores have been investigated at the single-molecule level. The anions track the Hofmeister ranking according to their influence upon the on-rate constant. An inverse relationship was demonstrated for the off-rate and the solubility of PEG. The difference among anions spans several hundredfold. Halogen anions play a very significant role in the interaction of PEG with nanopores although, unlike K⁺, they do not bind to PEG. The specific effect appears dominated by a hydration-dehydration process where ions and PEG compete for water. Our findings provide what we believe to be novel insights into physicochemical mechanisms involved in single-molecule interactions with nanopores and are clearly relevant to more complicated chemical and biological processes involving a transient association of two or more molecules (e.g., reception, signal transduction, enzyme catalysis). It is anticipated that these findings will advance the development of devices with nanopore-based sensors for chemical and biological applications.     

Sulfate anion stabilization of native ribonuclease A both by anion binding and by the Hofmeister effect

Data are reported for T(m), the temperature midpoint of the thermal unfolding curve, of ribonuclease A, versus pH (range 2-9) and salt concentration (range 0-1 M) for two salts, Na(2)SO(4) and NaCl. The results show stabilization by sulfate via anion-specific binding in the concentration range 0-0.1 M and via the Hofmeister effect in the concentration range 0.1-1.0 M. The increase in T(m) caused by anion binding at 0.1 M sulfate is 20 degrees at pH 2 but only 1 degree at pH 9, where the net proton charge on the protein is near 0. The 10 degrees increase in T(m) between 0.1 and 1.0 M Na(2)SO(4), caused by the Hofmeister effect, is independent of pH. A striking property of the NaCl results is the absence of any significant stabilization by 0.1 M NaCl, which indicates that any Debye screening is small. pH-dependent stabilization is produced by 1 M NaCl: the increase in T(m) between 0 and 1.0 M is 14 degrees at pH 2 but only 1 degree at pH 9. The 14 degree increase at pH 2 may result from anion binding or from both binding and Debye screening. Taken together, the results for Na(2)SO(4) and NaCl show that native ribonuclease A is stabilized at low pH in the same manner as molten globule forms of cytochrome c and apomyoglobin, which are stabilized at low pH by low concentrations of sulfate but only by high concentrations of chloride.     

Interactions of macromolecules with salt ions: an electrostatic theory for the Hofmeister effect

Salting-out of proteins was discovered in the nineteenth century and is widely used for protein separation and crystallization. It is generally believed that salting-out occurs because at high concentrations salts and the protein compete for solvation water. Debye and Kirkwood suggested ideas for explaining salting-out (Debeye and MacAulay, Physik Z; 1925;131:22-29; Kirkwood, In: Proteins, amino acids and peptides as ions and dipolar ions. New York: Reinhold; 1943. p 586-622). However, a quantitative theory has not been developed, and such a theory is presented here. It is built on Kirkwood's idea that a salt ion has a repulsive interaction with an image charge inside a low dielectric cavity. Explicit treatment is given for the effect of other salt ions on the interaction between a salt ion and its image charge. When combined with the Debye-Hückel effect of salts on the solvation energy of protein charges (i.e., salting-in), the characteristic curve of protein solubility versus salt concentration is obtained. The theory yields a direct link between the salting-out effect and surface tension and is able to provide rationalizations for the effects of salt on the folding stability of several proteins.     

The effect of Hofmeister anions and protein concentration on the activity and stability of some immobilized NAD-dependent dehydrogenases

The effect of several factors on the activity and stability of alcohol dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase, and 20beta-hydroxysteroid dehydrogenase, both free and immobilized on CNBr-activated Sepharose 4B, was investigated. Enzymes were im- mobilized under different conditions including various degrees of matrix activation, variable amounts of protein, in the presence, or in the absence of, additives (coenzymes, dithioth- reitol, salts). Activity recovery was in general satisfactorily high with 20beta-hydroxysteroid dehydrogenase, low with glyceraldehyde-3-phosphatedehydrogenase, and markedly linked to the concentration of immobilized protein with alcohol dehydrogenase. In the latter case the advantageous stabilizing effect of high enzyme concentrations was notably diminished by the parallel decrease of the effectiveness factor. The effect of high concentrations of anions of the Hofmeister series was examined. It was found that 1M phosphate and 0.5M sulfate dramatically stabilize both free and immobilized enzymes against inactivation by temperature and urea. K(m), values of apolar substrates were considerably lowered by the two anions while K(m) values of polar substrates were not affected. In some cases V(max) values also were influenced by high concentrations of these anions. The present results appear of interest particularly in view of enzyme utilization for analytical as well as for preparative purposes.     

Hofmeister ions control protein dynamics

Background

Recently, we have elaborated a thermodynamic theory that could coherently interpret the diverse effects of Hofmeister ions on proteins, based on a single physical parameter, the protein–water interfacial tension (Dér et al., Journal of Physical Chemistry B. 2007, 111, 5344–5350). This theory, implying a “liquid drop model”, predicts changes in protein conformational fluctuations upon addition of Hofmeister salts (containing either kosmotropic or chaotropic anions) to the medium.

Methods

Here, we report experimental tests of this prediction using a complex approach by applying methods especially suited for the detection of protein fluctuation changes (neutron scattering, micro-calorimetry, and Fourier-transform infrared spectroscopy).

Results

It is demonstrated that Hofmeister salts, via setting the hydrophobic/hydrophilic properties of the protein–water interface, control conformational fluctuations even in the interior of the typical membrane transport protein bacteriorhodopsin, around its temperature-induced, unusual α(II) → α(I) conformational transition between 60 and 90 °C. We found that below this transition kosmotropic (COOCH₃⁻), while above it chaotropic (ClO₄⁻) anions increase structural fluctuations of bR. It was also shown that, in each case, an onset of enhanced equilibrium fluctuations presages this phase transition in the course of the thermotropic response of bR.

Conclusions

These results are in full agreement with the theory, and demonstrate that predictions based on protein–water interfacial tension changes can describe Hofmeister effects and interpret protein dynamics phenomena even in unusual cases.

General significance

This approach is expected to provide a useful guide to understand the principles governing the interplay between protein interfacial properties and conformational dynamics, in general.     

Hofmeister effect in ion transport: reversible binding of halide anions to the roflamycoin channel.

We have studied the anion-dependent gating of roflamycoin ion channels using spectral analysis of noise in currents through multichannel planar lipid bilayers. We have found that in addition to low frequency current fluctuations that may be attributed to channel switching between open and closed conformations, roflamycoin channels exhibit a pronounced higher frequency noise indicating that the open channel conductance has substates with short lifetimes. This noise is well described by a Lorentzian spectrum component with a characteristic cutoff frequency that depends on the type of halide anions according to their position in the Hofmeister series. It is suggested that transitions between the substates correspond to a reversible ionization of the channel by a penetrating anion that binds to the channel structure, more chaotropic anions being bound for longer times. Within a framework of a two-substate model, the duration of the substate with reduced electrostatic barrier for cation current varies exponentially with anion electron polarizability. This explains two features of the roflamycoin channel reported earlier: the increase in apparent single-channel conductance along the series F- < Cl- < Br- < I- and the reverse of channel selectivity from anionic for KF to cationic for KI.     

Hofmeister effects in supramolecular and biological systems

Specific ion effects, representative of near-universal Hofmeister phenomena, are illustrated in three different systems. These are the formation of supramolecular assemblies from cyclodextrins, the optical rotation of L-serine, and the growth rate of two kinds of microorganisms (Staphylococcus aureus and Pseudomonas aeruginosa). The strong specific ion effects can be correlated with the anion polarizabilities and related physico-chemical parameters. The results show the relevance of dispersion (non-electrostatic) forces in these phenomena.     

Influence of anions and cations on the dipole potential of phosphatidylcholine vesicles: a basis for the Hofmeister effect

Anions and cations have long been recognized to be capable of modifying the functioning of various membrane-related physiological processes. Here, a fluorescent ratio method using the styrylpyridinium dyes, RH421 and di-8-ANEPPS, was applied to determine the effect of a range of anions and cations on the intramembrane dipole potential of dimyristoylphosphatidylcholine vesicles. It was found that certain anions cause a decrease in the dipole potential. This could be explained by binding within the membrane, in support of a hypothesis originally put forward by A. L. Hodgkin and P. Horowicz [1960, J. Physiol. (Lond.) 153:404-412.] The effectiveness of the anions in reducing the dipole potential was found to be ClO4- > SCN- > I- > NO3- > Br- > Cl- > F- > SO42-. This order could be modeled by a partitioning of ions between the membrane and the aqueous phase, which is controlled predominantly by the Gibbs free energy of hydration. Cations were also found to be capable of reducing the dipole potential, although much less efficiently than can anions. The effects of the cations was found to be trivalent > divalent > monovalent. The cation effects were attributed to binding to a specific polar site on the surface of the membrane. The results presented provide a molecular basis for the interpretation of the Hofmeister effect of lyotropic anions on ion transport proteins.     

Hofmeister effect underlying the quiescence of sperm motility in the vas deferens of the viviparous guppy Poecilia reticulata

Guppy sperm are immotile in the fluid (seminal plasma) of the vas deferens. We previously reported that the initiation of sperm motility is regulated by "Hofmeister solutes" in the isotonic medium. This indicates that chaotropes in solution activate the guppy sperm, whereas counteracting kosmotropes negate this activational effect and keep the sperm immotile. Here we show that seminal plasma has a strong inhibitory effect on sperm activation in response to chaotropes and multivalent ions, and that this inhibitory effect is due to kosmotropicity of the seminal plasma. These findings suggest a novel system of regulation of sperm motility in the guppy, a viviparious fish, in which the sperm are kept immotile in the vas deferens by a physicochemical effect (the Hofmeister effect) of the seminal plasma.     

Hofmeister效应与包含体的变性和复性

Hofmeister效应反映了溶质小分子通过与水分子的相互作用, 对蛋白质等生物大分子造成的结构上的影响.通过对此效应的深入研究, 可以从理论上解释许多常见的生理生化现象.蛋白质的变性、复性问题是与Hofmeister效应密切相关的生化基础课题. 目前重组蛋白生产过程中包含体的变性和复性问题为上述理论研究提供了广泛的应用空间.     

Experiments on the Hofmeister series in heart muscle

Summary The distinct effects which anions have on the automaticity of the heart may be used as a demonstration of the validity of theHofmeister series in living cells.The following procedure is chosen: Heart strips ofRana esculenta are first immersed inRinger's and thereafter in isotonic non-electrolyte solutions until automaticity ceases. By replacing 30 parts of the nonelectrolyte solution by an isotonic Na-salt solution automaticity will be restored. The ions follow theHofmeister series: Citrate, SO⁴, C1, Br, I, SCN in their effectiveness, SCN being the most powerful anion. This is not only evident in that the last members of the series restore automaticity which has ceased in the presence of anions preceding them in theHofmeister series but also in, the duration of activity produced by different Na-salts and frequently in the height of contraction.The experiment also succeeds in heart strips without spontaneous activity.If the sequence in which the ions are applied is reversed (from SCN to Citrate) only the first ion is effective. The experiments show that the automaticity of the heart muscle depends on anions in the same way as the excitability of voluntary striated muscles.Non-electrolytes which bring about a standstill of the heart show frequently first a slowing of the heart rate and an increase in the time of relaxation. The effects are reversible if Na-salts are added to non-electrolyte solutions.Aided by the National Research Council and the Research Fund of the University of Oregon.     

The effect of salt on the Michaelis Menten constant of the HIV-1 protease correlates with the Hofmeister series

The effect of different types of salt on the proteolytic activity of HIV-1 protease was studied. At a similar ionic strength, the enzyme activity changed according to the salting out effect of the ions used (Hofmeister series). Kinetic studies showed that a stronger salting out effect of the ions rather than the higher ionic strength per se increased the affinity to the substrate (Km) but in general did not alter the Kcat value.     

Effects of Hofmeister salts on the self-association of glucagon

The trimerization constants of glucagon at pH 10.6 in 0.76 M K2HPO4 have been calculated from circular dichroism data between 5 and 50 degrees C. The free energy, enthalpy, and entropy of transfer have been evaluated from the current results and published data in 0.20 M phosphate. The free energies of transfer are derived completely from an increase in the entropy of transfer, since the enthalpy of transfer is less favorable at all temperatures. These parameters are compared with those of various model groups and compounds: CH2, peptide, methane, ethane, and the 1--13 N-terminal fragments of ribonuclease. The effects of fluoride and chloride on the self-association of glucagon have been compared with that of phosphate at 25 degrees C. These effects are consistent with the binding of approximately one molecule of salt to the trimer and a systematic decrease in the number of water molecules bound to the trimer compared to the monomer for the series K2HPO4, KF, and KCl.     

Interactions between macromolecules and ions: The Hofmeister series

The Hofmeister series, first noted in 1888, ranks the relative influence of ions on the physical behavior of a wide variety of aqueous processes ranging from colloidal assembly to protein folding. Originally, it was thought that an ion's influence on macromolecular properties was caused at least in part by 'making' or 'breaking' bulk water structure. Recent time-resolved and thermodynamic studies of water molecules in salt solutions, however, demonstrate that bulk water structure is not central to the Hofmeister effect. Instead, models are being developed that depend upon direct ion-macromolecule interactions as well as interactions with water molecules in the first hydration shell of the macromolecule.     

Franz Hofmeister, sein Leben und Wirken

Ohne Zusammenfassung