Review
Ions in water: Characterizing the forces that control chemical processes and biological structure

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Abstract

The continuum electrostatics model of Debye and Hückel [P. Debye and E. Hückel, On the theory of electrolytes. I. Freezing point depression and related phenomena., Phys. Z. 24 (1923) 185–206.] and its successors utilize a macroscopic dielectric constant and assume that all interactions involving ions are strictly electrostatic, implying that simple ions in water generate electric fields strong enough to orient water dipoles over long distances. However, solution neutron and X-ray diffraction indicate that even di- and tri-valent ions do not significantly alter the density or orientation of water more than two water molecules (5 Å) away. Therefore the long range electric fields (generated by simple ions) which can be detected by various resonance techniques such as fluorescence resonance energy transfer over distances of 30 Å (about 11 water diameters) or more must be weak relative to the strength of water–water interactions. Two different techniques indicate that the interaction of water with anions is by an approximately linear hydrogen bond, suggesting that the dominant forces on ions in water are short range forces of a chemical nature.

Introduction

A quantitative understanding of the forces in aqueous solution that control chemical processes and give rise to biological structure is essential for progress in such disparate fields as process design in the chemical industry; drug design in the pharmaceutical industry; and the modeling of biological processes such as signal transduction via ionic fluxes and protein folding, localization, and function in health and disease. We have studied the interaction of ions with water as a way to understand these forces, and used the Hofmeister series [2], [3] to systemize our results. The Hofmeister series orders ions as a monotonic function of their surface charge density and thus water affinity, with the strength of water–water interactions separating strongly hydrated from weakly hydrated species; it is most convenient to generate a separate series for anions and for cations.

Continuum electrostatics models such as that of Debye and Hückel [1] utilize a macroscopic dielectric constant and assume that all interactions involving ions are strictly electrostatic, implying the existence of long range electric fields strong relative to the strength of water–water interactions. In these models, ions are often thought of as point charges and water as a dipole which orients in the long range electric field; such models are unable to accurately describe such simple ion-specific behaviors as their tendency to form contact ion pairs, which is a major determinate of the solubility of specific salts and of the role of specific ions in biological systems. For example, models employing a macroscopic dielectric constant predict that all ions are strongly hydrated and will be repelled from nonpolar surfaces by image forces. In fact, weakly hydrated ions do exist (e.g., ammonium, chloride, potassium, and the positively charged amino acid side chains) and actually adsorb to nonpolar surfaces [3], [4], [5] and interfaces [6], [7]. The driving force for this adsorption of weakly hydrated ions to an air/water interfaces has been shown by electrospray ionization mass spectrometry to be the release of weakly bound water to become strongly interacting bulk [8], a process not included in the calculations utilizing the macroscopic dielectric constant. Sophisticated microscopic calculations have indicated a role for the polarizability [9], [10] of weakly hydrated ions (as opposed to their dehydration energy) and dispersion forces [11] in driving them to neutral interfaces. Microscopic calculations also find a role for the polarizability of water in driving the weakly hydrated Cl ion to an air/water interface [9], [10], [12], but since “polarizability appears to be important primarity for its role in facilitating a larger average dipole moment on the water model” [12] and the interaction of water with Cl is via an approximately linear hydrogen bond rather than a dipolar interaction [13], [14], [15], it is difficult to evaluate the significance of these calculations. The continuum electrostatic models also assume that anions and cations have exactly analogous interactions with water, which is not consistent with the data in Fig. 5.

Over the last 25 years, new approaches have been developed to study the hydration of ions in the Hofmeister series, and a very different picture of how ions interact with water and other ions is emerging. This new perspective provides simple explanations for the tendency of specific ions to form contact ion pairs and to manifest other behaviors.

In this review we survey the information available on how ions interact with water, and find that the known properties of ion–water interactions are inconsistent with the assumptions underlying continuum electrostatics. We arrive at the important conclusion that the dominant forces on ions in water are short range forces of a chemical nature (mediated by electrons in atomic orbitals) and that the long range electric fields generated by simple ions are weak relative to the strength of water–water interactions. We demonstrate that many processes involving ions in water are actually dominated by hydration–dehydration, a non-electrostatic component which is not included in the calculations utilizing a macroscopic dielectric constant.

Section snippets

Over what distance do ions in water have an influence on water?

Simple ions in water generate long range electric fields which can be detected by various resonance techniques, such as fluorescence resonance energy transfer, over distances of 30 Å (about 11 water diameters) or more [16]. It has usually been assumed that the long range electric fields generated by simple ions in water are strong enough to orient water dipoles over long distances. But solution neutron and X-ray diffraction techniques developed in the 1970s and applied to various ions in water

Defining an abbreviated Hofmeister series for anions and for cations

The IA cations and VIIA halides of the periodic table of the elements form abbreviated Hofmeister series and each can be separated into strongly hydrated (small size, high surface charge density) and weakly hydrated (large size, low surface charge density) species relative to the strength of water–water interactions:kosmotropes H+, Li+, Na+ // K+, Rb+, Cs+ chaotropes(strongly hydrated) F- // Cl-, Br-, I- (weakly hydrated)“//” indicates the strength of water–water interactions; it is the

What is the evidence for the chemical nature of ion–water interactions?

Cl is known to be weakly hydrated because coordinated water molecules exchange on a timescale of less than 10 11 s and because it has a negative Jones–Dole viscosity B coefficient. Even so, solution neutron diffraction by isotopic substitution has been used to show apparently well defined geometry of the six water molecules coordinated to the ion; each water molecule has a linear hydrogen bond (within experimental error) with Cl, indicative of a primarily chemical interaction (a dipolar

“Volcano plots” illustrate the dominant forces on ions in water

We shall interpret Fig. 6 to indicate that oppositely charged ions with equal water affinity tend to come together in solution to form contact ion pairs whereas oppositely charged ions with differing water affinities tend to stay apart. We shall attribute the release of heat to the formation of strong bonds and the uptake of heat to the breakage of strong bonds, and shall assume that the strongest interactions in the system will tend to dominate the behavior of the system. In aqueous salt

Biological evidence for the short range nature of the dominant forces generated by ions in water

We shall now examine three biological systems whose behavior has been thought to be controlled by long range electric fields, and present the evidence for actual control by short range forces. (A) First, we shall examine the binding of negatively charged ligands to negatively charged regions of proteins; (B) second, we shall examine the role of charged amino acid side chains in globular protein stability; (C) and third, we shall examine the origins of “ionic strength” effects.

Conclusion

In conclusion, solution neutron diffraction, gas phase infrared vibrational predissociation spectroscopy, X-ray absorption spectroscopy, and ab initio molecular orbital studies indicate that water interacts with ions via a chemical bond, and that water is affected over only a short distance from simple, small ions (i.e., < 5 Å). This chemical interaction involves substantial charge transfer to solvent for strongly hydrated ions of high surface charge density, resulting in delocalization of

Acknowledgements

KDC thanks George R. Stark, R. Dan Camerini-Otero, Frank T. Robb, and W. Jon Lederer. GWN thanks his many colleagues involved in the neutron scattering experiments which were carried out at the Institut Laue Langevin (ILL) with the help of staff scientists. He is particularly grateful to Adrian Barnes and Chris Dempsey (Bristol University), Stuart Ansell and Alan Soper (Rutherford Appleton Laboratory), Phil Mason (Cornell University), and Gabriel Cuello and Henry Fischer (ILL). He also

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