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.[1]

Hofmeister discovered a series of salts that have consistent effects on the solubility of proteins and (it was discovered later) on the stability of their secondary and tertiary structure. Anions appear to have a larger effect than cations, and are usually ordered

\mathrm{F^{-} \approx SO_{4}^{2-} > HPO_{4}^{2-} > acetate > Cl^{-} > NO_{3}^{-} > Br^{-} > ClO_{3}^{-} > I^{-} > ClO_{4}^{-} > SCN^{-}}

(This is a partial listing; many more salts have been studied.) The order of cations is usually given as

\mathrm{NH_{4}^{%2B} > K^{%2B} > Na^{%2B} > Li^{%2B} > Mg^{2%2B} > Ca^{2%2B} > guanidinium}

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.[2]

Early members of the series increase solvent surface tension and decrease the solubility of nonpolar molecules ("salting out"); in effect, they strengthen the hydrophobic interaction. By contrast, later salts in the series increase the solubility of nonpolar molecules ("salting in") 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 (which are charged and have strong dipole moments) and may even bind specifically (e.g., phosphate and sulfate binding to ribonuclease A). 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.[3]

References

  1. ^ F.Hofmeister Arch. Exp. Pathol. Pharmacol. 24, (1888) 247-260.
  2. ^ Zhang Y, Cremer PS (2006). "Interactions between macromolecules and ions: The Hofmeister series". Current opinion in chemical biology 10 (6): 658–63. doi:10.1016/j.cbpa.2006.09.020. PMID 17035073. 
  3. ^ Baldwin RL. (1996). "How Hofmeister ion interactions affect protein stability". Biophys J 71 (4): 2056–63. Bibcode 1996BpJ....71.2056B. doi:10.1016/S0006-3495(96)79404-3. PMC 1233672. PMID 8889180. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1233672.