The Role of Ionic Liquids in Protein Folding/Unfolding Studies

Abstract

Ionic liquids (ILs) have emerged as novel solvent medium for several biotechnological processes in vitro. The use of ILs starts from protein extraction to catalysis to folding/ unfolding studies. ILs are becoming the most favorite non-aqueous medium for protein studies due to their unique ionic combinations (cation + anion) and tunable physical properties. In this context, several research results have been published that use of pure or aqueous IL solutions as stabilizer for proteins. Hence, herein, in this chapter, we present a collection of research work that focuses on the importance of ILs (and their mixture) in protein stabilities. In addition, we have also reviewed the unique properties of ILs as counteracting solvents for cold-induced denaturation and also their refolding properties. This report will definitely generate a new understanding for the ILs, their importance and applicability in protein folding studies.that is now considered as the first IL is ethylammonium nitrate ([C 2 H 5 NH 3 ][NO 3 ], EAN) and was prepared by Paul Walden in 1914 and has a melting point of 12°C [8]. After a long gap, the major studies of room temperature molten salts of pyridinium halides with aluminum chloride (AlCl 3 ) were made in the 1940s by a group led by Frank Hurley and Tom Weir at Rice University [9]. Later, alkylimidazolium salts (C n mim) + were also reported in the early 1980s [10]. An excellent short history of the birth of ILs, which covers the crucial moments of this area, is presented by John S. Wilkes [11].In its initial revolutionary stage, ILs were vastly considered in analytical chemistry based on their unique and tunable physical properties. Since then, synthesis of a large number of multifunctional ILs has been a prime interest for synthetic chemists [12,13]. In this context, varieties of task-specific ILs have been synthesized and the advantages of their physical properties have been reported in an open literature [14]. Common ILs include ammonium, phosphonium, sulfonium, guanidinium, pyridinium, imidazolium and pyrrolidinium cations. The most common anions are chloride, bromide, tetrafluoroborate, hexafluorophosphate, trifluoromethanesulfonyl, bis(trifluoromethanesulfonyl)imide, dicyanamide and alkyl sulfate anions. These ILs have some unique properties such as negligible vapor pressure, good thermal stability, tunable viscosity and miscibility with water, a wide electrochemical window, high conductivity and high heat capacity [15][16][17]. These physical properties make IL a promising material in numerous fields, for example, their use in electrochemical devices and replacements for several organic reactions [18,19]. Gordon [20], Parvulescu and Hardacre [21] and Crowhurst et al. [22] pointed out that there is an obvious advantage in performing many reactions in ILs due to the improvement in reaction activity, selectivity and yield. An in-depth literature survey reveals that there tremendously exist a large number of scholarly articles as well as elegant reviews that explicitly elucidate the various s...

On the Stability of Proteins Solvated in Imidazolium-Based Ionic Liquids Studied with Replica Exchange Molecular Dynamics

“…ILs have been proposed as green alternatives to conventional organic solvents, which are known to be harmful to the environment. Although it has been shown that certain families of ILs and those that contain long alkyl chains possess increased levels of toxicity and may pose a threat to the environment, suitable design can diminish their toxicity levels. − For instance, having short alkyl chains ( n < 4) and polar functional groups are often useful in reducing toxicity. ,, Moreover, research in this area revealed that it is possible to generate ILs which are nontoxic and biodegradable. ,− Furthermore, ILs which are safe to use in contact with skin have also been found. , The versatility of ILs imparted through the change of the ion constituents and combination is one of their key merits, enabling the possibility to tweak physical properties for various applications.…”

“…In the recent decade, there has been an intense focus on the use of ILs as solvents for biomolecules such as proteins, enzymes, and nucleic acids, such as DNA. ,− Numerous studies have shown that when ILs are used as media for biomolecules, properties and behavior of the solute are enhanced, as compared to using conventional solvents, such as water or organic solvents. ,,,− The review by Patel et al (ref ) gives a comprehensive summary of the application of ILs as solvents for proteins, whereas the review by Sivapragasam et al (ref ) provides an overview of the development in the field of ILs used in combination with biomolecules.…”

Competitive Effects of Anions on Protein Solvation by Aqueous Ionic Liquids

“…Ionic liquids, composed of large and asymmetric ions, offer a diverse array of intermolecular interactions with water and the various chemical moieties commonly found on protein surfaces . These versatile liquids have gradually replaced conventional and hazardous organic solvents in applications related to protein stability and tuning enzyme activity, for example. ,− However, fewer studies have delved into systems involving salt mixtures compared to single-salt solutions …”