Hofmeister series


The Hofmeister series or lyotropic series is a classification of ions in order of their ability to salt out or salt in proteins. The effects of these changes were first worked out by Franz Hofmeister, who studied the effects of cations and anions on the solubility of proteins.
Hofmeister discovered a series of salts that have consistent effects on the solubility of proteins and on the stability of their secondary and tertiary structure. Anions appear to have a larger effect than cations, and are usually ordered
The order of cations is usually given as
The mechanism of the Hofmeister series is not entirely clear, but does not seem to result from changes in general water structure, instead more specific interactions between ions and proteins and ions and the water molecules directly contacting the proteins may be more important. Recent simulation studies have shown that the variation in solvation energy between the ions and the surrounding water molecules underlies the mechanism of the Hofmeister series.
Early members of the series increase solvent surface tension and decrease the solubility of nonpolar molecules ; in effect, they strengthen the hydrophobic interaction. By contrast, later salts in the series increase the solubility of nonpolar molecules and decrease the order in water; in effect, they weaken the hydrophobic effect. The salting out effect is commonly exploited in protein purification through the use of ammonium sulfate precipitation.
However, these salts also interact directly with proteins and may even bind specifically. Ions that have a strong 'salting in' effect such as I− and SCN− are strong denaturants, because they salt in the peptide group, and thus interact much more strongly with the unfolded form of a protein than with its native form. Consequently, they shift the chemical equilibrium of the unfolding reaction towards unfolded protein.
The denaturing of proteins by an aqueous solution containing many types of ions is more complicated as all the ions can act, according to their Hofmeister activity, i.e., a fractional number specifying the position of the ion in the series in terms of its relative efficiency in denaturing a reference protein. The concept of Hofmeister ionicity Ih has been invoked by Dharma-wardana et. al. where it is proposed to define Ih as a sum over all ionic species, of the product of the ionic concentration and a fractional number specifying the "Hofmeister strength" of the ion in denaturing a given reference protein. The concept of ionicity used here has to be distinguished from ionic strength as used in electrochemistry, and also from its use in the theory of solid semiconductors