Co-solvents (in watersolvent) are defined askosmotropic (order-making) if they contribute to the stability and structure of water-water interactions. In contrast,chaotropic (disorder-making) agents have the opposite effect, disrupting water structure, increasing the solubility of nonpolar solvent particles, and destabilizing solute aggregates.[1] Kosmotropes cause water molecules to favorably interact, which in effect stabilizes intramolecular interactions inmacromolecules such asproteins.[1]
Ionic kosmotropes tend to be small or have high charge density. Some ionic kosmotropes areCO2−
3,SO2−
4,HPO2−
4,Mg2+
,Li+
,Zn2+
andAl3+
. Large ions or ions with low charge density (such asBr−
,I−
,K+
,Cs+
) instead act aschaotropes.[2] Kosmotropicanions are morepolarizable and hydrate more strongly than kosmotropiccations of the same charge density.[3]
A scale can be established if one refers to theHofmeister series or looks up thefree energy ofhydrogen bonding () of the salts, which quantifies the extent of hydrogen bonding of an ion in water.[4] For example, the kosmotropesCO2−
3 andOH−
have between 0.1 and 0.4J/mol, whereas the chaotropeSCN−
has a between −1.1 and −0.9.[4]
Recent simulation studies have shown that the variation in solvation energy between the ions and the surrounding water molecules underlies the mechanism of theHofmeister series.[5][6] Thus, ionic kosmotropes are characterized by strong solvation energy leading to an increase of the overall cohesiveness of the solution, which is also reflected by the increase of the viscosity and density of the solution.[6]
Ammonium sulfate is the traditional kosmotropic salt for the salting out of protein from an aqueous solution. Kosmotropes are used to induce protein aggregation in pharmaceutical preparation and at various stages of protein extraction and purification.[7][citation needed]
Nonionic kosmotropes have no net charge but are very soluble and become very hydrated. Carbohydrates such astrehalose andglucose, as well asproline andtert-butanol, are kosmotropes.