Hofmeister Order of Anions on Protein Stability Originates from Lifshitz-van der Waals Dispersion Interaction with...

The mechanism underpinning the Hofmeister order of anions on protein stability and other physical and biological processes has been a mystery since its discovery in 1888. In the present study, we investigated electrostatic and Lifshitz-van der Waals (L-vdW) dispersion (electrodynamic) interactions between Hofmeister salts and four monomeric globular proteins. It is shown that structure-stabilizing salts exerted positive L-vdW pressure, whereas structure-destabilizing salts exerted negative L-vdW pressure on proteins. The relative order of the L-vdW pressure followed the Hofmeister series and it overshadowed the electrostatic pressure at high salt concentrations. The net change in the thermal denaturation temperature (ΔT_d) of proteins in 0.8 M Hofmeister salt solutions followed a linear relationship (r² > 0.8) with the net electrodynamic pressure regardless of the physicochemical differences between proteins. This study also revealed that segregation of anions into structure stabilizers and destabilizers depended on the dielectric susceptibility of the anion in the ultraviolet region: ions having absorbtion spectrum in the ultraviolet region (e.g., Cl^-, Br^-, I^-, and SCN^-) exerted a negative electrodynamic pressure, whereas those with absorbtion spectrum only in the infrared region, for example, SO₄^2-, exerted a positive electrodynamic pressure. The lack of ultraviolet absorption of SO₄^2- ions was because of quenching of ultraviolet radiation by water at below 170 nm.