Proteins in Ionic Liquids: Current Status of Experiments and Simulations

Abstract

In the last two decades, while searching for interesting applications of ionic liquids as potent solvents, their solvation properties and their general impact on biomolecules, and in particular on proteins, gained interest. It turned out that ionic liquids are excellent solvents for protein refolding and crystallization. Biomolecules showed increased solubilities and stabilities, both operational and thermal, in ionic liquids, which also seem to prevent self-aggregation during solubilization. Biomolecules can be immobilized, e.g. in highly viscous ionic liquids, for particular biochemical processes and can be designed to some extent by the proper choice of the ionic liquid cations and anions, which can be characterized by the Hofmeister series.

Ionic liquids for oral insulin delivery

“…Ionic liquids interact with various hydrophilic and hydrophobic amino acids of a protein through an intricate balance of hydrogen bonds, disulfide bridges, hydrophobic effects, and ionic interactions (48). When mixed with other liquids such as water, a more complex interplay between ions occurs that, depending on the nature of ions, can result in formation of micelles or microemulsions (48). A prolonged and higher oral plasma concentration of poorly water-soluble drugs dispersed in ILs was also reported by Williams et al (32).…”

Protein Crystallization in Ionic-Liquid Hydrogel Composite Membranes

“…Crystallization supported by bare membrane (IL-HCM 0) and by standard plastic sitting-drop cradle (REF) was carried out for comparison (see Section 2.2). Among proteins usually used for testing new crystallization methods or screenings, we have chosen GI, whose crystallization in standard conditions, in the presence of ILs as additives [7] and of hydrogels [28], is well known.…”

“…Simulations have shown that the concentration of cations at the protein surface exceeds that of anions, since cations do not contribute to the anionic hydrogen-bonded network with water. Excess cations interact with the protein surface at negatively charged areas, through strong Coulomb interactions, and at non-polar surface areas, through dispersion interactions mediated by their alkyl chains [7]. Instead anions strongly interact with positively charged areas through hydrogen bonds and Coulomb interactions.…”

“…Both cations and anions have favorable solvation sites at the polar protein surface, and interact stronger with protein than water, with a higher residence time for anions and higher mobility for cations. As a result of the complex framework of IL-protein surface interactions, protein solubility is affected enough to induce protein precipitation and crystallization [7]. The impact of ILs on the crystallization process is even more pronounced than for precipitation, as they contribute to slowing down of the vapor transfer rate and to control crystal growth velocity [8].…”

“…The impact of ILs on the crystallization process is even more pronounced than for precipitation, as they contribute to slowing down of the vapor transfer rate and to control crystal growth velocity [8]. For example, IL-based additives were found to improve crystal size, X-ray diffraction resolution, tolerance to impurities during the crystallization, and, more importantly, to enable polymorph selection, thus making the crystallization process more selective [7].…”