Salting out and in

My latest story for Physical Review Focus concerns calculations of the tendency of various ions dissolved in water to accumulate at its surface.

This is a really old problem, discussed by some of the giants of physical chemistry. In the 1930s, for example, later Nobel winner Lars Onsager and others suggested that the termination of the electrical polarization at the surface of the water would give rise to an "image charge"--a surface charge of the same sign as the ion that creates an electric field just like that of a point charge at the mirror-image location on the other side of the interface. The repulsion from this image charge, they suggested, would keep ions away from the surface.

People have apparently suspected for decades that things can't be that simple, because different ions alter the surface tension to different degrees, indicating that they are changing the energy of the surface, presumably by being part of it. But only in the past decade or so have new experiments and simulations shown that some simple negative ions like halogens can be stable at the surface. Such ions at the surface of atmospheric droplets could be important catalysts, for example for breaking down ozone.

The two closely related Physical Review Letters that motivated the Focus story attribute the attractiveness of the surface position of a large negative ion to its internal polarizability. The internal rearrangement of charge, they say, allows the ion to retain much of the electrostatic attraction to nearby water molecules without creating a big hole in the water. However, I talked to another researcher who attributes the stabilization of the surface ion to a distortion it induces in the shape of the nearby surface. These both seem like potentially important effects, and both may play a role in the ultimate understanding.

The difference between the two could be important, though, for a related and even older phenomenon: the effect of various added salts on dissolved proteins. In 1888, Hofmeister ranked a series of ions in terms of their effectiveness in precipitating the proteins, and the order of the series mirrors that which was later found for the effects of ions on surface tension.

"Salting out" occurs when an added salt reduces the solubility of a protein, presumably by tying up water molecules and raising its effective concentration. This effect has been used for decades to create the protein crystals needed for structural studies like x-ray crystallography.

In contrast, "salting in" makes the protein more soluble, but may denature it. Salts that have this effect may alter the repulsion between water and the hydrophobic regions of the protein. This repulsion is critical for maintaining the shape of proteins that naturally occur in the bulk of the cell, since that shape generally presents hydrophilic regions to the solution and shelters hydrophobic regions inside. (Proteins that naturally occur in membranes, by contrast, generally expose a hydrophobic stripe where they are embedded in the non-aqueous center of the membrane sheet.)

The polarizability of ions at the protein-water interface could have an important effect on this repulsion. In contrast, since the water-protein interface is entirely within the liquid, changing the shape of the interface wouldn't seem to be an option.

It is true that many proteins take on their final shapes only in the presences of "chaperone" proteins, which can also help fix them up if they become denatured. Nonetheless, any insight into the interactions between water and proteins could be very important to understanding why they fold the way they do, and how circumstances might change that folding.