Aqueous Biphasic Systems Comprising Natural Organic Acid‐Derived Ionic Liquids

Abstract

Despite the progress achieved by aqueous biphasic systems (ABSs) comprising ionic liquids (ILs) in extracting valuable proteins, the quest for bio‐based and protein‐friendly ILs continues. To address this need, this work uses natural organic acids as precursors in the synthesis of four ILs, namely tetrabutylammonium formate ([N4444][HCOO]), tetrabutylammonium acetate ([N4444][CH3COO]), tetrabutylphosphonium formate ([P4444][HCOO]), and tetrabutylphosphonium acetate ([P4444][CH3COO]). It is shown that ABSs can be prepared using all four organic acid‐derived ILs paired with the salts potassium phosphate dibasic (K2HPO4) and tripotassium citrate (C6H5K3O7). According to the ABSs phase diagrams, [P4444]‐based ILs outperform their ammonium congeners in their ability to undergo liquid–liquid demixing in the presence of salts due to their lower hydrogen‐bond acidity. However, deviations to the Hofmeister series were detected in the salts’ effect, which may be related to the high charge density of the studied IL anions. As a proof of concept for their extraction potential, these ABSs were evaluated in extracting human transferrin, allowing extraction efficiencies of 100% and recovery yields ranging between 86 and 100%. To further disclose the molecular‐level mechanisms behind the extraction of human transferrin, molecular docking studies were performed. Overall, the salting‐out exerted by the salt is the main mechanism responsible for the complete extraction of human transferrin toward the IL‐rich phase, whereas the recovery yield and protein‐friendly nature of these systems depend on specific “IL-transferrin” interactions.