Current Opinion in Colloid & Interface Science 15 (2010) 34–39

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Current Opinion in Colloid & Interface Science

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Specific ion effects in colloidal and biological systems

Werner Kunz ⁎Institute of Physical and Theoretical Chemistry, University of Regensburg, D-93040 Regensburg, Germany

⁎ Tel.: +49 941 943 40 44; fax: +49 941 943 45 32.E-mail address: Werner.Kunz@chemie.uni-regensbu

1359-0294/$ – see front matter © 2009 Elsevier Ltd. Aldoi:10.1016/j.cocis.2009.11.008

a b s t r a c t

a r t i c l e i n f o

Article history:Received 20 September 2009Accepted 19 November 2009Available online 27 November 2009

Keywords:Hofmeister seriesIonsSaltsInterfacesIon associationIon hydrationKosmotropic ionsChaotropic ionsProteinsLipidsSugars

During the last ten years significant progress has been made in the understanding of specific ion effects. Onthe one hand new ideas about the origin of these effects came up, and on the other hand new experimentaltechniques were developed so that now even the ion concentration profile near surfaces can be measuredwith some confidence. In the present review some of the most important new progresses are summarisedand critically discussed, especially in the context of colloidal and biological systems.

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1. Introduction

Franz Hofmeister's work on specific salt effects more than120 years ago is today still the reference for any investigation in thisfield [1•]. In a series of papers he and his co-workers demonstrated theconsequence of a whole bunch of salts on phenomena like precip-itation of proteins and mineral oxides, swelling of biological materialetc. Before him, Poiseuille was probably the first to systematicallystudy specific ion effects in solution. In 1847 he published a paperabout the viscosity of aqueous solutions containing different salts [2].

It is interesting to note that Hofmeister was a pharmacologist.Indeed, salts have an important impact e.g. on digestion, the nervoussystem and the properties of blood. In the 19th century, it was noteasy to understand such complex systems. But, as far as ion effectswere concerned, they were easy to measure. Swelling and precipita-tion can be detected with the naked eye. Osmotic pressures andelectrical conductivity change by orders of magnitude when ions areadded to an aqueous solution, and this was easy to measure already inthe 19th century.

In sharp contrast to the readily reproducible experiments, theconclusions made by Hofmeister are far from being trivial. Still todaythere is a debate about the relative importance of direct ion–ion

interactions and of ion–water interactions to explain or even topredict these effects. Some scientists are convinced that the properdescription of dispersion forces will finally solve the problem, othersthink that the proper geometry of ions or charged headgroups and ofwater is decisive.

Especially in colloidal science and biology, the number ofpublications dealing with specific ion effects is innumerable. In avery recent book a summary of the current knowledge of these effectsis attempted [3••]. Often a typical ordering, the so-called Hofmeisterseries, is found, as it is shown in Fig. 1.

However, it is often forgotten that Hofmeister proposed series onlyfor salts and not for individual ions. Further, regarding all thepublished data, it turns out that there is not a single and uniqueseries. Not only some ions can change their position in the series,there can also be a reversed series or a bell-shaped series, dependingon the respective system property that is examined. Some commonions are even difficult to integrate into the system. This is the case forexample for the guanidinium ion. This ion is poorly hydrated much asthe ammonium ion, so it should be classified somewhere on the leftside of the series shown in Fig. 1. However, it is known thatguanidinium is a strong denaturant and according to this property itshould be placed on the right side. As it was studied in details byMason and colleagues, it is obviously the particular geometry (chargedistribution and flat structure) that is very important for thisparticular behaviour [4,5•]. It can self-aggregate (stacking) in contrastto ammonium, and it can be considered as a very small hydrotrope

Fig. 1. Typical ordering of cations and anions in a Hofmeister series [3••].

35W. Kunz / Current Opinion in Colloid & Interface Science 15 (2010) 34–39

having some parts that preferentially interact with water and anotherpart that is more hydrophobic. Very recently, the difference betweenthe self-aggregation of guanidiniumwas used to explain in details thereasons why also arginine side-chains (bearing guanidinium groups)self-associate overcoming the electrostatical repulsion.

In this context, it is interesting to have a look at the cationHofmeister series in Fig. 1 and to compare it with the anion series. Inthe case of cations the series goes from soft weakly hydrated ions onthe left to hard, strongly hydrated ions on the right. In the case of theanions, it is the opposite. As we will see, this difference can be partlyexplained by the different charged groups being present on theaccessible surface of biological molecules such as proteins. Bycontrast, concerning the solubility of organic or low polar moleculessuch as benzene or gases like oxygen and CO2, soft, polarisable andorganic ions are mostly salting-in and hard and highly charged ionsare mostly salting-out, independently of the sign of their charge [6].

Concerning the classification of ions, the term structure-makingand structure-breaking was used over many years. However, it issomewhat misleading. According to recent experimental findings, itseems that at least monovalent ions do not influence the structure ofwater beyond the first hydration shell [7]. Therefore there is nosignificant long-range structuring of water due to the presence of ions.In the present paper we just keep the denominations “kosmotropic”and “chaotropic” for convenience and for historical reasons withoutattributing any sense to the original meaning.

In general, specific cation effects are less pronounced than specificanion effects, because anions have stronger interactions with waterthan cations of the same size and absolute charge density. However,this is only true when ion–water interactions are dominant for thespecific ion effects. When direct ion–ion or ion–charged headgroupinteractions are dominant, specific cation effects can be of the sameorder of magnitude as specific anion effects.

All these findings are only valid for essentially inorganic ions. Forquaternary longer-chain ammonium ions the situation is different.Roughly speaking, the longer the chains the more denaturating arethe organic cations. But here, the detailed geometry of these ions andthe nature of the charged headgroups (acting as counterions) on themacromolecules can significantly alter the position of these ions in theseries.

It should be noted that recently also various ions from Ionic Liquidswere studied with respect to their denaturating behaviour [8]. Withthe increasing importance of salts that are liquid at room temperature,

the insertion of such ions into the Hofmeister series is most importantand useful.

2. What are the important interactions?

Following the pioneering work by Yaminsky and Ninham [9], itwas supposed that dispersion interactions between ions in solutioncan satisfactorily explain ion specificity. However, it turned out thatthis is not so, at least not with simplified and straight-forwardprimitive models that neglect the structure of water. For example, it isimpossible to describe properly the experimentally determinedsurface tension increments with reasonable ion polarisabilities [10].

Of course, it is by far not trivial to estimate ion polarisabilities insolutions, although much effort has been invested in the last years toobtain at least approximate values [11]. Nevertheless, it is evident forchemists that iodide is more polarisable than chloride. But in order todescribe properly the surface tension changes with salt concentration,the opposite had to be assumed for sodium halides in the simplifieddispersion interaction models published so far [12].

The next question is if ion polarisabilities are important per se.Although the first molecular dynamics simulations by Jungwirth,Tobias [13••], and Dang and Chang [14] pointed in this direction, this ismuch less clear today. Probably, the contributions of ion polarisabil-ities are widely covered by the attractive part of the Lennard-Jonespotentials and a further and refined modelling is not necessary.

So what remains to properly describe specific ion effects?

a) Although it may appear trivial, the first and most important pa-rameter is the charge density, i.e. the ratio between charge and ionradius. The question is however to knowwhat is the proper radius. Isit Pauling's radius or is it the radius including the first hydrationsphere? This is by far a non-trivial and not yet finally resolvedquestion, because themodelling of ion specificities crucially dependson these values. As could be shown recently byHorinek et al. [15] theusually taken potential parameters for ions in aqueous solutionsshould be optimised. As a consequence, several conclusions drawnfrom earlier simulations have to be looked atwith care. For example,Jungwirth's and Tobias' and Dang's finding that even small inorganicions can be attracted to the water–air interface is very probablycorrect— and in themeantime confirmed by experiments— but thisresult can be also obtained in simulations by optimised interactionseven without considering explicitly the ion polarisability.

b) At interfaces, the structuring of water is decisive. For example, it iscounterintuitive that acids lower the surface tension of water. Theexperimental finding suggests that there is some overall propen-sity of protons to the surface of water, which is truly anunexpected image for every chemist. However, it is often forgottenthat the contact of water with air is not energetically favourable(water has a high surface energy). Further, hydronium ions cannotbe hydrated so favourably in water due to their particular chargedistribution and geometry. Therefore it is a reasonable assumption(and supported by simulation results from Jungwirth's group [16])that H3O+ ions can enter the first water layer near to the airsurface, where their hydration and geometry is energeticallyslightly more favourable than in the bulk.Another example is the adsorption of ions to hydrophobicinterfaces. Lund et al. [17•] recently published a very interestingsimulation in which they considered the adsorption of halide ionsto large hydrophobic spheres that bear some positive charges onisolated patches of their interface. The question was if the anionswill adsorb preferentially to the cationic sites or elsewhere.Intuitively, one might expect that the anions will be electrostat-ically attracted by the opposite charge. However, again this is asimplified consideration not taking account the structure of water.Around the hydrophobic surface the water layering (the “hydro-phobic structuring” of water) is energetically not very favourable.

Fig. 2. Division of the group IA cations and the VIIA halide anions into strongly hydratedkosmotropes and weakly hydrated chaotropes. The ions are drawn approximately toscale. A virtual water molecule is represented by a zwitterion of radius 1.78 Å for theanionic portion and 1.06 Å for the cationic portion. In aqueous solution, Li+ has 0.6tightly attached water molecules, Na+ has 0.25 tightly attached water molecules, F has5.0 tightly attached water molecules, and the remaining ions have no tightly attachedwater (picture redesigned from [20••]).

36 W. Kunz / Current Opinion in Colloid & Interface Science 15 (2010) 34–39

Therefore, it is not astonishing that large ions of low charge densitysuch as iodide have a significant propensity to the hydrophobicparts, more or at least as strong as to the positive patches. This is afinding that in the meantime is not only predicted by independentsimulations, but also by experimental findings.What can we learn from these results? First of all we must takeinto account the detailed structure of water. Simplified solvent-averaged models in the tradition of the Debye–Hückel approachand related Poisson–Boltzmann theories are not adequate todescribe specific ion effects unless some information about thewater structure is introduced. Second, electrostatic effects may notalways be dominant, the chemical structure and geometry of thewhole system can overcome even electrostatic repulsions. Forexample, phosphate ions can be buried in negatively charged sitesof proteins in cases where the geometry and the resultinginteractions of the amino acid residues in the protein pocketscreate an overall energetically favourable environment.

c) Ion properties depend strongly on the environment and in particularon the counterions or headgroups in their vicinity. This is bad newsfor engineerswhowant to havewell-defined ion specific parametersto describe their properties in solutions. It was intuitively the rightstrategy followed by Hofmeister to give only salt-specific and notion-specific ordering. It also explains why there is not one andunique Hofmeister series. A good example for this somewhatdisappointing statement is given in [5•]. It is discussed there whythe denaturating effect of guanidinium is largely reduced by thecounterion sulphate due to strong cation–anion interactions,whereas the interaction of guanidinium is much less strong withchloride as counterion so that in the case of guanidinium chloride,the cation keeps its denaturation efficiency.Even in the case of a property as simple as the free energy (activitycoefficients) of simple electrolyte solutions, it must be admitted thatthe combination of cations with different anions can reverse theirordering [18].

d) The structure and chemical composition of macromolecules mustbe known to have a chance to predict any specific ion effects. Forexample, ion–protein interactions cannot be described properly bysimplified models that consider proteins as a sphere with auniform charge distribution. This seems to be evident; neverthe-less such approaches were often tried, also within the last years.What should be done, by contrast, is to consider the number of thevarious amino acid residues that are accessible to the ions and towater in a protein. With this, a sort of “protein surface” can bedefined and then the interaction between the ions and theindividual types of amino acids must be considered [19•].

e) Specific ion effects are salt concentration dependent and, espe-cially in the case of proteins, strongly pH dependent. Usually, atvery low salt concentrations (b0.1 M) electrostatics is dominant(although even here specific ion effects are sometimes found),whereas at intermediate concentrations (0.1–N2 M) specific ioneffects are often measured, because here the electrostatic interac-tions are significantly screened. At very high concentrations, usu-ally most of the water is captured in the ion hydration spheres andthen even chaotropic ions can become salting-out.

Taking together all these points, it seems rather hopeless to getsome general idea about specific ion effects. Everything seems to beinterconnected and rather special than general. However, the situ-ation is slightly more favourable. A useful concept was introducedsome years ago by Kim D. Collins [20••] and recently extended andwillbe discussed in the next section.

3. Collins' concept of matching water affinities

Collins presented an amazingly simple and convincing concept. Asall simple concepts it should be considered with a grain of salt and

care must be taken not to overinterpret the predictions or theunderlying assumptions. In the light of the preceding discussion in thelast section, it is evident that such complex phenomena like specificion effects cannot be fully described within a simple model.Nevertheless, we will see that the idea of Collins allows one to un-derstand a multitude of experimental results in biology and colloidalscience.

Collins' model is known as the “concept of matching wateraffinities”. Ions are considered, to first approximation, as a spherewith a point charge in the centre. When the ions are small, thesurrounding water molecules are tightly bound (the ions are hard orkosmotropic), whereas when the ions are big, the hydration shell isonly loosely bound (the ions are soft or chaotropic). The discrimina-tion between both types comes from the relative strength of the ion–water interactions compared to water–water interactions, as illus-trated in Fig. 2.

To explain the different types of interaction, Collins makes thefurther assumption that two strongly hydrated small ions of oppositecharge experience a very strong reciprocal attraction. Consequently,they can come together forming direct ion pairs and expelling thehydration spheres between them. In the case of weakly hydrated softions, the situation is very different, but the result is the same: theelectrostatic attraction between them is much smaller than betweenkosmotropes, however, the hydration spheres are so loosely boundthat the chaotropic ions can also form direct ion pairs expelling alsothe hydration water between them. The interaction of one hard andone oppositely charged soft ion is then straightforward: here, theattraction by the soft ion is not strong enough that the hard ion losesits hydration shell. As a consequence, a soft/hard ion pair is alwaysseparated by water and cannot form strong ion pairs, see Fig. 3.

This concept is a particular application of the more general rule“like seeks like” that often can be applied in chemistry [21•]. A moststriking success of this concept is the qualitatively correct predictionof the reversal of the Hofmeister series of activity coefficients ofsimple aqueous electrolyte solutions when changing simply thecounterion, see Fig. 4a,b. For bromide solutions the activity coeffi-cients increase with increasing charge density of the cations, whereasfor the acetates (and also other anion series such as hydroxide orfluoride) it is just the opposite ordering. For a long time peoplespeculated about the possible origin. Robinson and Stokes [22]supposed a “localised hydrolysis” but this was not really convincing.Instead, Collins' concept delivers a chemically intuitive explanation:According to this concept acetate should form inner ion pairs or atleast a slightly higher association with other hard ions such as lithiumand should have less interaction with ions of low charge density like

Fig. 3. Ion size controls the tendency of oppositely charged ions to form inner sphere ionpairs. Small ions of opposite sign spontaneously form inner sphere ion pairs in aqueoussolution; large ions of opposite sign spontaneously form inner sphere ion pairs inaqueous solution; and mismatched ions of opposite sign do not spontaneously forminner sphere ion pairs in aqueous solution. A largemonovalent cation has a radius largerthan 1.06 Å; a large monovalent anion has a radius larger than 1.78 Å. Pictureredesigned according to [20••].

37W. Kunz / Current Opinion in Colloid & Interface Science 15 (2010) 34–39

rubidium. This is indeed the case. Higher association is directly re-flected by lower values of activity coefficients. For bromide ions thesituation is just the opposite: bromides are of low charge density andshould therefore and according to Collins' concept interact more with

Fig. 4. a) Activity coefficients of HBr and several alkali bromide solutions as a function ofsalt concentration. b) Activity coefficients of several alkali acetate solutions as afunction of salt concentration. Values taken from [22].

counterions of low charge density such as rubidium and less withcations of high charge density such as lithium. This is precisely what isreflected by the activity coefficients. It should be noted that this conceptis also in agreement with theoretical results found by Friedman and co-workers almost 40 years ago [23]. They performed integral equationcalculationswith an interaction potential based on the so-called Gurneymodel. This model describes the possible overlap of hydration spheresaround the ions. The energy interaction parameters Friedman et al.found with this model were at that time not interpretable, but can bequalitatively understood in light of Collins' ideas.

In biology and colloidal chemistry, the interaction of ions withcharged headgroups is an important part of specific ion effects.Therefore, it is of importance to have at least qualitatively a sort ofHofmeister series for such headgroups. Recently, such series werepublished [24••], they are reproduced in Fig. 5.

The proposed series are deduced from both molecular dynamicssimulation results and, especially for cationic headgroups, fromexperimental results, notably from ion-pair chromatography studies.

As shown and further discussed in Refs. [24••] and [18], theapplication of Collins' concept of matching water affinities togetherwith these headgroup series allows one to understand numerousexperimental results. For example, it becomes clear why the criticalmicellar concentration sharply increases for alkylammonium surfac-tants, when bromide is replaced by acetate as a counterion. The

Fig. 5. “Like seeks like”: hard headgroups preferentially interact with hard counterions,soft headgroups preferentially interact with soft counterions. a) Cations with negativelycharged headgroups. b) Anions with positively charged headgroups.

• of special interest.•• of outstanding interest.

38 W. Kunz / Current Opinion in Colloid & Interface Science 15 (2010) 34–39

alkylammonium headgroup associates less strongly with the hardacetate than with the soft bromide counterion and therefore theeffective charge is higher on the alkylammonium in the presence ofacetate. The concept also explains why the kosmotropic–chaotropicordering is reversed for cations and anions in Fig. 1. Proteins containmany hard anionic headgroups such as carboxylates and essentially softcationic headgroups such as ammonium. Therefore, in an average, theinteraction of proteins with hard cations and soft anions is morepronounced than with soft cations and hard anions. It seems that theconcept can even explain the interactions of ions with phospholipidswhich bear a rather hard phosphore and a soft choline group. Here asimilar chaotropic–kosmotropic reversal between the cation and anionseries was found as for proteins [25•].

It should be repeated that this concept is only a first approximationand that real physics is muchmore complicated. For example Dzubiellaet al. [26] could show how much more subtle the interactions are. Theformation of direct ion pairs in contrast to solvent-separated ion pairsseems to be in reality a tiny difference in the ion–ion interaction po-tential, but with significant consequences. Further, for example car-boxylates have important contributions coming from their particulargeometry rather than simply from the charge density. Alkylphosphatesmust sometimes considered as rather hard and sometimes as rather softheadgroups depending on the counterions and the properties that areconsidered. So the chemist's (or biologist's) simplified image should notbe overinterpreted.

At the end of this section, it should be mentioned that Collins'concept can also serve as a starting point to understand the interactionsof ionswithpolar, but unchargedpolymers, a subject that is important infood chemistry, cosmetics andmany other fields. In a very elegant workLivney et al. considered the interactions of cations and anions withpolyacrylamide in aqueous solutions and in gels. They propose a simple,but convincing model of interaction and a useful scaling model for theosmotic pressure exerted by the polymer in the presence of ions [27•].For the interactions of water, ions, and macromolecules, see also theimportant work by P. S. Cremer's group [28,29].

4. Specific ion effects in food relevant systems

Over the years quite a few studies were published concerning theinfluence of “kosmotropic” and “chaotropic” ions on biologicalsystems. As far as lipid membranes are concerned, some literature isgiven in the introduction of Ref. [25•].

Most food relevant studies concern sugars or starch and proteins.Salts have a remarkable influence on the gelatinisation and the rhe-ological properties of starches. However, since starch is not charged,the interactions are more subtle than the interactions of ions withcharged headgroups. In Ref. [30] the observed results are attributed toi) anion mediated modified water–polymer interactions. This is aclassical way to interpret Hofmeister's “water-withdrawing effect”mostly by kosmotropes and is easy to predict and understand. ii)Disruption of polymer chain aggregation by the interaction of cationswith the hydroxyl groups of the starch molecules. The first effect ofthe anions can increase or decrease the gelatinisation temperatureand the rheological storage module depending on the nature of theanions (respectively kosmotropic or chaotropic) and the second effectdecreases both properties.

Concerning proteins, some studies are devoted to the influence ofions to gluten. Gluten is of course of utmost importance in foodchemistry, but it is very difficult to infer general results from thesestudies. Nevertheless, an interesting attempt is described in Ref. [31],where also a certain Hofmeister-like classification of amino acids isgiven.

Several protein isolates were also studied in view of theirmodification by the presence of salts [32–34]. In particular, theirrheological behaviour, water absorption capacity, gelation concentra-tion, and foaming behaviour were investigated. The results essentially

are in agreement with Hofmeister's old classification and can beexplained now in light of the “like seeks like” model with ions andcharged headgroups. As far as interactions of proteins with ions isconcerned, more information can be found e.g. in Ref. [19•] and thereference cited there, especially in the Introduction.

Finally, it should be stressed that protein stabilising or denaturat-ing effects are not limited to charged species, another hint at the factthat electrostatics is not all and that non-electrostatic interactions canoften be at least as important as Coulomb interactions. In this contextRef. [35] contains a nice study about the strong denaturant urea andthe strong kosmotrope trehalose.

Finally, although not directly related to food chemistry, it should benoted that tremendous work on ion–protein interactions can be foundin the literature of leather making, i.e. tanning. Over the centuries,people gained a lot of empirical experience. Especially in the 1920snumerous papers appeared about this subject. But it is only since fewyears that scientists got amore physically based inside into ion–collageninteractions, especially into the “pickling” process. In this context Ref.[36] should be cited, because in this interesting experimental study onthe thermal stability of calf skin collagen I in salt solutions, one cannicelydistinguish the concentration range of essentially electrostatic from theintermediate range of salting-in or -out and from the concentratedsolutions, where even chaotropes become salting-out. There are alsosome computer simulations [37] on the swelling of collagen in waterand salt solutions, although some interpretations of the results probablymust be reconsidered in view of the newest above-mentioned concepts.How pH-sensitive are these ion–collagen interactions is studied indetails in a recent experimental work [38].

5. Outlook

It is amazing to see the progress that was made within the last tento fifteen years concerning the understanding of specific ion effects.The different opinions about their origin seem to converge more andmore. Both the new opportunities of today's computer power and themultitude of experimental results have contributed to this optimisticstatement. But most important: some scientists try to distillate nowthe essentials out of all this innumerable studies in order to get somegeneralised rules or at least a physical understanding of the observedor predicted trends.

What remains to do?We should come to a sort of tables indicating,in which case and for which property which series or combination ofions/headgroups can be expected. In order to do this, we should alsoinclude sugars, amino acid residues and osmolytes in the series, aswell as polar, uncharged headgroups. We should also include ionscurrently occurring in Ionic Liquids for cases where they are in contactwith water. Finally, for practical reasons, we should try to putnumbers on the ions/headgroups with some (certainly not unique)combination rules. Such numbers were most useful in other contexts,for example to define the local polarity of solvents with the ETnumbers [39]. Without such a distillation of information, the presentknowledge of specific ion effects will remain inapplicable for most ofthe scientists and engineers facing practical problems with ionspecificity in their systems.

References and recommended reading

•[1] Kunz W, Henle J, Ninham BW. ‘Zur Lehre von der Wirkung der Salze’ (about the

science of the effect of salts): Franz Hofmeister's historical papers. Curr OpinColloid Interface Sci 2004;9:19–37.A summary of Hofmeister's papers on salteffects is given and two of his most relevant papers are translated into English.

[2] Poiseuille JL. Sur le mouvement des liquides de nature très différente dans lestubes de très petits diamètres. Ann Chim Phys 1847;21:76–110.

39W. Kunz / Current Opinion in Colloid & Interface Science 15 (2010) 34–39

••[3] Kunz W (Ed.). Specific Ion Effects. World Scientific Publishing, 2009.[4] Mason PE, Neilson GW, Enderby JE, Saboungi ML, Dempsey CE, MacKerell AD,

Brady JW. The structure of aqueous guanidinium chloride solutions. J Am ChemSoc 2004;126:11462–70.

•[5] Mason PhE, Dempsey ChE, Vrbka L, Heyda J, Brady JW, Jungwirth P. Specificity of ion–

protein interactions: complementary and competitive effects of tetrapropylammo-nium, ganidinium, sulfate, and chloride ions. J Phys Chem B 2009;113:3227–34.

[6] McDevit WF, Long FA. Activity coefficients of nonelectrolyte solutes in aqueoussalt solutions. Chem Rev 1952;51:119–69.

[7] Omta AW, Kropman MF, Woutersen S, Bakker HJ. Negligible effect of ions on thehydrogen-bond structure in liquid water. Science 2003;301:347–9.

[8] Constantinescu D, Weingärtner H, Herrmann Ch. Protein denaturation by ionicliquids and the Hofmeister series: a case study of aqueous solutions ofribonuclease A. Angew Chem 2007;46:8887–9.

[9] Ninham BA, Yaminsky V. Ion binding and ion specificity: the Hofmeister effect andOnsager and Lifshitz theories. Langmuir 1997;13:2097–108.

[10] Kunz W, Belloni L, Bernard O, Ninham BW. Osmotic coefficients and surfacetensions of aqueous electrolyte solutions: role of dispersion forces. J Phys Chem B2004;108:2398–404.

[11] Serr A, Netz R. Polarizabilities of hydrated and free ions derived from DFTcalculations. Int J Quantum Chem 2006;106:2960–74.

[12] BoströmM, KunzW, Ninham BW. Hofmeister effects in surface tension of aqueouselectrolyte solution. Langmuir 2005;21:2619–23.

••[13] Jungwirth P, Tobias DJ. Specific ion effects at the air/water interface. Chem Rev

2006;106:1259–81.[14] Dang LX, Chang TM. Molecular mechanism of ion binding to the liquid/vapor

interface of water. J Phys Chem B 2002;106:235–8.[15] Horinek D, Mamatkulov Sh I, Netz RR. Rational design of ion force fields based on

thermodynamic solvation properties. J Chem Phys 2009;130:124507/1–124507/21.[16] Buch V, Milet A, Vacha R, Jungwirth P, Devlin JP. Water surface is acidic. Proc Nat

Acad Sci (USA) 2007;104:7342–7.

•[17] Lund M, Vrbka L, Jungwirth P. Specific ion binding to nonpolar surface patches of

proteins. J Am Chem Soc 2007;130:11582–3.[18] Kunz W, Neueder R. An Attempt of a General Overview; in Ref. [3].

•[19] Vrbka L, Jungwirth P, Bauduin P, Touraud D, Kunz W. Specific ion effects at protein

surfaces: a molecular dynamics study of bovine pancreatic trypsin inhibitor andhorseradish peroxidase in selected salt solutions. J Phys Chem B 2006;110:7036–43.In the introduction of this paper, a list of most relevant publications is given aboutHofmeister effects on proteins.

••[20] Collins KD. Ions from the Hofmeister series and osmolytes: effects on proteins in

solution and in the crystallization process. Methods 2004;34:300–11.

•[21] Lyklema J. Simple Hofmeister series. Chem Phys Lett 2009;467:217–22.[22] Robinson RA, Stokes RH. Electrolyte SolutionsSecond Revised ed. London:

Butterworth; 1970.

[23] Ramanathan PS, Friedman HL. Study of a refined model for aqueous 1–1electrolytes. J Chem Phys 1971;54:1086–99.

••[24] Vlachy N, Jagoda-Cwiklik B, Vácha R, Touraud D, Jungwirth P, Kunz W. Hofmeister

series and specific interactions of charged headgroups with aqueous ions. AdvColloid Polym Sci 2009;146:42–7.

•[25] Garcia-Celma JJ, Hatahet L, KunzW, Fendler K. Specific anion and cation binding to

lipid membranes investigated on a solid supported membrane. Langmuir2007;23:10074–80.

[26] Dzubiella J, Fyta M, Horinek D, Kalcher I, Netz RR, Schwierz N. Ion-Specificity:From Solvation Thermodynamics to Molecular Simulations and Back; in Ref. [3].

[27] Livney YD, Portnaya I, Faupin B, Ramon O, Cohen Y, Cogan U, Mizrahi S.Interactions between inorganic salts and polyacrylamide in aqueous solutions andgels. J Polym Sci 2003;41:508–19.

[28] Zhang YJ, Furyk S, Bergbreiter DE, Cremer PS. Specific ion effects on the watersolubility of macromolecules: PNIPAM and the Hofmeister series. J Am Chem Soc2005;127:14505–10.

[29] Chen X, Yang T, Kataoka S, Cremer PS. Specific ion effects on interfacial waterstructure near macromolecules. J Am Chem Soc 2007;129:12272–9.

[30] Ahmad FB, Williams PA. Effect of salts on the gelatinization and rheologicalproperties of sago starch. J Agric Food Chem 1999;47:3359–66.

[31] Larsson H, Hedlund U. On the swelling properties of gluten in the presence of saltsand reduced pH. Spec Publ - R Soc Chem 2004;295:247–50.

[32] Lawal OS, Afolabi TA, Adebowale KO, Ogunsanwo1 BM, Bankole SA. Effect ofselected Hofmeister anions on functional properties of protein isolate preparedfrom lablab seeds (Lablab purpureus). J Sci Food Agric 2005;85:2655–9.

[33] Lawal OS. Kosmotropes and chaotropes as they affect functionality of a proteinisolate. Food Chem 2006;95:101–7.

[34] Bowland EL, Foegeding EA, Hamann DD. Rheological analysis of anion-inducedmatrix transformations in thermally induced whey protein isolate gels. FoodHydrocoll 1995;9:57–64.

[35] Barreca D, Bellocco E, Laganà G, Leuzzi U, Magazù S, Migliardo F, Galtieri A.Spectroscopic investigation of structure-breakers and structure-makers onornithine carbamoyltransferase. Food Chem 2008;106:1438–42.

[36] Komsa-Penkova R, Koynova R, Kostov G, Tenchov BG. Thermal stability of calf skincollagen type I in salt solutions. Biochim Biophys Acta 1996;1297:171–81.

[37] Bulo RE, Siggel L, Molnar F, Weiss H. Modeling of bovine type-i collagen fibrils:interaction with pickling and retanning agents. Macromol Biosci 2007;7:234–40.

[38] Freudenberg U, Behrens SH,Welzel PB, Müller M, GrimmerM, Salchert K, Taeger T,Schmidt K, Pompe W, Werner C. Electrostatic interactions modulate theconformation of collagen I. Biophys J 2007;92:2108–19.

[39] Dimroth K, Reichardt Ch, Siepmann Th, Bohlmann F. Pyridinium N-phenolbetainesand their use for the characterization of the polarity of solvents. Ann Chem(Liebig) 1963;661:1–37.