The study of the interactions of salts and osmolytes with macromolecules in aqueous solution originated with experiments concerning protein precipitation more than 100 years ago. Today, these solutes are known to display recurring behavior for myriad biological and chemical processes. Such behavior depends both on the nature and concentration of the species in solution. Despite the generality of these effects, our understanding of the molecular-level details of ion and osmolyte specificity is still quite limited. Here, we review recent studies of the interactions between anions and urea with model macromolecular systems. A mechanism for specific ion effects is elucidated for aqueous systems containing charged and uncharged polymers, polypeptides, and proteins. The results clearly show that the effects of the anions are local and involve direct interactions with macromolecules and their first hydration shell. Also, a hydrogen-bonding mechanism is tested for the urea denaturation of proteins with some of these same systems. In that case, direct hydrogen bonding can be largely discounted as the key mechanism for urea stabilization of uncollapsed and/or unfolded structures.

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Chemistry of Hofmeister anions and osmolytes.

The classical Derjaguin–Landau–Verwey–Overbeek (DLVO) theory of colloids, and corresponding theories of electrolytes, are unable to explain ion specific forces between colloidal particles quantitatively. The same is true generally, for surfactant aggregates, lipids, proteins, for zeta and membrane potentials and in adsorption phenomena. Even with fitting parameters the theory is not predictive. The classical theories of interactions begin with continuum solvent electrostatic (double layer) forces. Extensions to include surface hydration are taken care of with concepts like inner and outer Helmholtz planes, and “dressed” ion sizes. The opposing quantum mechanical attractive forces (variously termed van der Waals, Hamaker, Lifshitz, dispersion, nonelectrostatic forces) are treated separately from electrostatic forces. The ansatz that separates electrostatic and quantum forces can be shown to be thermodynamically inconsistent. Hofmeister or specific ion effects usually show up above ≈10−2 molar salt. Parameters to accommodate these in terms of hydration and ion size had to be invoked, specific to each case. Ionic dispersion forces, between ions and solvent, for ion–ion and ion–surface interactions are not explicit in classical theories that use “effective” potentials. It can be shown that the missing ionic quantum fluctuation forces have a large role to play in specific ion effects, and in hydration. In a consistent predictive theory they have to be included at the same level as the nonlinear electrostatic forces that form the skeletal framework of standard theory. This poses a challenge. The challenges go further than academic theory and have implications for the interpretation and meaning of concepts like pH, buffers and membrane potentials, and for their experimental interpretation. In this article we overview recent quantitative developments in our evolving understanding of the theoretical origins of specific ion, or Hofmeister effects. These are demonstrated through an analysis that incorporates nonelectrostatic ion–surface and ion–ion dispersion interactions. This is based on ab initio ionic polarisabilities, and finite ion sizes quantified through recent ab initio work. We underline the central role of ionic polarisabilities and of ion size in the nonelectrostatic interactions that involve ions, solvent molecules and interfaces. Examples of mechanisms through which they operate are discussed in detail. An ab initio hydration model that accounts for polarisabilities of the tightly held hydration shell of “cosmotropic” ions is introduced. It is shown how Hofmeister effects depend on an interplay between specific surface chemistry, surface charge density, pH, buffer, and counterion with polarisabilities and ion size. We also discuss how the most recent theories on surface hydration combined with hydrated nonelectrostatic potentials may predict experimental zeta potentials and hydration forces.

Hofmeister effects: interplay of hydration, nonelectrostatic potentials, and ion size

Synthesis and swelling behavior of xanthan-based hydrogels

Following up on scattered reports on interactions of conventional chaotropic ions (for example, I- , SCN- , ClO4 - ) with macrocyclic host molecules, biomolecules, and hydrophobic neutral surfaces in aqueous solution, the chaotropic effect has recently emerged as a generic driving force for supramolecular assembly, orthogonal to the hydrophobic effect. The chaotropic effect becomes most effective for very large ions that extend beyond the classical Hofmeister scale and that can be referred to as superchaotropic ions (for example, borate clusters and polyoxometalates). In this Minireview, we present a continuous scale of water-solute interactions that includes the solvation of kosmotropic, chaotropic, and hydrophobic solutes, as well as the creation of void space (cavitation). Recent examples for the association of chaotropic anions to hydrophobic synthetic and biological binding sites, lipid bilayers, and surfaces are discussed.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/anie.201804597

The Chaotropic Effect as an Assembly Motif in Chemistry.

The hydration force between large molecules or large surfaces is built on weak perturbation of many solvent molecules. The structure of the surface sets boundary conditions on solvent while structural forces within the solvent set the range. For this collection of essays, we focused on forces between surfaces at nanometer separations. It is instructive to distinguish primary hydration, the binding of water and perturbation within a few layers, from secondary hydration related to redistribution of solutes. The subject is still basically empirical, lacking satisfactory theory and sufficient measurement.

Hydration forces: Observations, explanations, expectations, questions

https://www.cell.com/biophysj/pdf/S0006-3495(07)71416-9.pdf

Effects of Monovalent Anions of the Hofmeister Series on DPPC Lipid Bilayers Part I: Swelling and In-Plane Equations of State

Effects of Monovalent Anions of the Hofmeister Series on DPPC Lipid Bilayers Part II: Modeling the Perpendicular and Lateral Equation-of-State

In this work, we use Langmuir monolayers of dipalmitoyl phosphatidylcholine (DPPC) as model systems to enhance the understanding of specific anion effects in physicochemical and biological systems. The 298 K isotherms (equation of state, EOS) of DPPC over solutions of a range of sodium salts depend strongly on the type and concentration of the salt in the subphase. We focus in particular on the liquid expanded phase region of the DPPC EOS and assume that the deviation of the isotherms over electrolyte solutions from that over pure water is due entirely to the charging of the lipid monolayer by the ions. We then examine the ability of a range of phenomenological continuum models to explain the pressure increase in the presence of electrolytes. The important finding is that insoluble lipid monolayers allow the discrimination between possible modes of ion−lipid interaction. Chemical binding models, simple or modified, cannot fit the range of data presented in this work. Both dispersion interaction and partit...

Liquid expanded monolayers of lipids as model systems to understand the anionic hofmeister series: 1. A tale of models.

Monolayers, bilayers and micelles of zwitterionic lipids as model systems for the study of specific anion effects

In the preceding paper of this series [ Leontidis , E. ; Aroti , A. ; Belloni , L. J. Phys. Chem. B 2009 , 113 , 1447 ], we considered and modeled the increase of the surface pressure of dipalmitoyl phosphatidylcholine (DPPC) monolayers over electrolyte solutions of various monovalent sodium salts. The experimental results for salts with large, less hydrophilic anions can be successfully described by models treating ionic specificity either as specific partitioning in the interfacial lipid layer or as a result of ion-lipid dispersion interactions. However, the results for salts with more hydrophilic anions, such as chloride and fluoride, cannot be fitted by any of these models, while they clearly demonstrate the existence of a specific sodium-DPPC interaction. In the present paper, we first prove that the experimental results for sodium fluoride (NaF) can be fitted by a model that is based on simultaneous complexation of sodium ions with up to three lipid molecules, as suggested by recent molecular dynamics simulations. We then return to the experimental results of sodium salts with more hydrophobic anions, treated in the preceding paper, and prove that these can be fitted equally well with a complex model, which accounts for both sodium complexation with the lipid head groups and anion partitioning within the lipid monolayers. The partitioning parameters obtained from this more complete model correlate well with several measures of ion specificity, such as ionic volume, von Hippel chromatographic parameters, or viscosity B-coefficients. A model for these partitioning chemical potentials is created based on the competition of cavity and ion hydration terms. The model leads to an excellent correlation of the partitioning chemical potentials with a function of the ionic radius, suggesting that specific anion effects on this lipid model system are mostly a matter of ionic size. Two notable exceptions from this correlation are thiocyanate and acetate ions, the charge distribution of which is not spherically symmetric, so that they are expected to have orientational-dependent interactions with the water-lipid interface. The implications of the present results on ion specificity in general are discussed.

A. Aroti

Papers

Effects of Monovalent Anions of the Hofmeister Series on DPPC Lipid Bilayers Part I: Swelling and In-Plane Equations of State

Effects of Monovalent Anions of the Hofmeister Series on DPPC Lipid Bilayers Part II: Modeling the Perpendicular and Lateral Equation-of-State

Liquid expanded monolayers of lipids as model systems to understand the anionic hofmeister series: 1. A tale of models.

Monolayers, bilayers and micelles of zwitterionic lipids as model systems for the study of specific anion effects

Liquid expanded monolayers of lipids as model systems to understand the anionic hofmeister series: 2. Ion partitioning is mostly a matter of size.