New perspective into how salts promote or hinder solubility

What is it about?

The phenomena known as the Hofmeister effect has been known for over 100 years. It describes the situation whereby some salts can lead to an increase in the solubility of proteins, known as "salting-in", and that others can cause a dramatic decrease in solubility, known as "salting-out". In some situations, however, salts that normally “salt-in” a protein (i.e. make it more soluble) have the opposite effect, that is they cause a protein to "salt-out" known as the reverse Hofmeister effect. This study reveals happens at the molecular level when a large molecule experiences an increase or decrease in solubility in the presence of different salts. Using a synthetic "host" molecule we show that large, charge diffuse (weakly hydrated) anions bind to hydrophobic pockets according to their normal Hofmeister behavior. However, these same anions can promote the reverse Hofmeister effect when they bind to a separate cationic binding site. This results in ion-pairing with significantly attenuated solubility and the compounds "salt-out" of solution.

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Why is it important?

The direct and reverse Hofmeister effect have far reaching applications in many areas such as protein crystallization, and human health and disease (e.g. prion diseases). This is the first example to correlate macroscopic salting-in and salting-out with molecular-level specificity for binding sites.