The Effect of Electrolyte on Protein Solubility

Just as the Debye-Huckel theory can be used to explain the solubility minimum at a pH = pi, it also explains the role of electrolyte concentration. Referring to Eq. (12.3), the electrolyte concentration affects the value of k, the inverse Debye length, as shown below  

Salting-out is not well understood. One popular explanation for this effect relies on the relative hydration of the protein versus bulk electrolyte. In this model, the electrolyte is assumed to bind bulk water as water of hydration near the ion s surface. Likewise, the protein needs to be hydrated with water. As the bulk electrolyte and the protein compete for bulk water to hydrate their respective surfaces, the protein become partially dehydrated and prefers to fill such exposed surface (dehydrated surface) with other protein molecules thus, facilitating crystal contacts. Thus, the solubility of the protein is reduced as the electrolyte is added to the protein solution. The effectiveness of ions (cations and anions) to cause phase separation (or lower solubility) has been documented by 

Cations Cs (least effective) -Rb-K-Na-Li (most effective) Anions SCN (least effective) -I-Br-Cl-F-NOs-chlorate (most effective) 

Cations Li (least effective) -Na-K-NH4-Mg (most effective) Anions SO4 (least effective) -P04-C00-citrate- tartrate-bicarbon-ate-chromate-Cl-NOs-chlorate-SCN (most effective) 

the general ordering of ions shows some consistency, but there is not a clear agreement as to the proper order of ions for effectiveness in causing crystallization. Cohn (1925) empirically modeled the salting out effect using the following equation  

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