Hofmeister Series of Ions: A Simple Theory of a Not So Simple Reality.

In their Perspective 1 based on recent work of the group, 2 Xie and Gao outline a simple theory for rationalizing the specific effects of ions on proteins, i.e., the Hofmeister series. 3 Their approach is thermodynamic, based on activity coefficients, surface tension and solubility data. It is also systematic, detailing individual contributions to the overall protein salting-out/salting-in and stabilizing/destabilizing action of salts and osmolytes. In particular, the authors choose to focus on the effects of interactions of ions with the protein backbone and on ion pairing in the solution. Traditionally, the Hofmeister series, the original version of which is depicted in Figure 1, has been rationalized in terms of the ability of certain ions (kosmotropes) to organize water molecules and the lack thereof for other ions (chaotropes). 4 Such a long-range water ordering contradicts, however, observations on salt solutions from modern spectroscopic measurements and molecular dynamics simulations, which point to a local influence of ions on water. 5, 6 Moreover, the traditional approach leaves a key player – the protein itself, completely out of the picture. As a result, it does not allow for explanation why salting out of some proteins (most notably lysozyme at low to normal pHs and up to moderate salt concentration) follows a reversed rather than normal Hofmeister ordering. 7