# Kosmotropic

Solutes are defined as kosmotropic if they contribute to the stability and structure of water-water interactions. Kosmotropes cause water molecules to favorably interact, which also stabilizes intermolecular interactions in macromolecules such as proteins.

## Ionic Kosmotropes

Ionic kosmotropes tend to be small or have high charge density. Some ionic kosmotropes are sulfate, phosphate, 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.

A scale can be established if one refers to the Hofmeister series or looks up the free energy of hydration ($\Delta G_{\rm hydr}$) of the salts. The more negative $\Delta G_{\rm hydr}$, the more kosmotropic the salt.

## Applications

Ammonium sulfate is the traditional kosmotropic salt for the salting out of protein from an aqueous solution. Kosmotropes are used to prevent protein aggregation in pharmaceutical preparation and at various stage of protein extraction and purification. They act by stabilizing native intramolecular protein interactions, thus out-competing the intermolecular interactions that lead to aggregation.

## 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.