Co-solvents (in water solvent) are defined as kosmotropic (order-making) if they contribute to the stability and structure of water-water interactions. Kosmotropes cause water molecules to favorably interact, which also (in effect) stabilizes intramolecular interactions in macromolecules such as proteins. Chaotropic agents (disorder-makers) have the opposite effect, disrupting water structure, increasing the solubility of nonpolar solvent particles, and destabilizing solute aggregates.
Contents
Ionic kosmotropes
Ionic kosmotropes tend to be small or have high charge density. Some ionic kosmotropes are CO2−
3, SO2−
4, HPO2−
4, magnesium(2+), lithium(1+), zinc (2+) and aluminium (+3). Large ions or ions with low charge density (such as bromide, iodide, potassium(1+), caesium(1+)) instead act as chaotropes. Kosmotropic anions are more polarizable and hydrate more strongly than kosmotropic cations of the same charge density.
A scale can be established if one refers to the Hofmeister series or looks up the free energy of hydrogen bonding (
3 and OH−
have
has a
Applications
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.
Nonionic kosmotropes
Nonionic kosmotropes have no net charge but are very soluble and become very hydrated. Carbohydrates such as trehalose and glucose, as well as proline and tert-butanol, are kosmotropes.