Heparin-like native protein aggregate dissociation by 1-alkyl-3-methyl imidazolium chloride ionic liquids

Abstract

At room temperature, ionic liquids (ILs) 1-alkyl-3-methyl imidazolium chloride (alkyl: ethyl, butyl, hexyl and octyl) are observed to exhibit aggregate dissociation behavior of native proteins. This is similar to the well known protein aggregation inhibitor and aggregate dissociation molecule heparin. Dynamic light scattering (DLS) experiments performed on three model proteins bovine serum albumin (BSA), β-lactoglobulin (β-Lg) and immunoglobulin (IgG) revealed that on addition of ILs the fractal aggregates of proteins (apparent maximum hydrodynamic radius Rmax and fractal dimension df=1.5±0.2) dissociated into oligomers (hydrodynamic radius Rh) following an exponential decay profile with time, Rh=Rmaxexp(−kat) The dissociation constant ka has been correlated to hydrophobicity index (H-index) of the protein concerned. Thus, if the combined contributions of dissociation constant and hydration effect on secondary structure are taken into account together, [C8mim][Cl] with BSA, [C2mim][Cl] with β-Lg and IgG, rank as the best aggregation reversal agent (ARA) amongst all other ionic liquid samples examined. The additional advantage of the used ILs over heparin is the release of mobile Cl− ions to the solution. This lead to the increased solution entropy, thereby, providing stability to the final dispersions.