Contemporary Advancement of Cholinium-Based Ionic Liquids for Protein Stability and Long-Term Storage: Past, Present, and Future Outlook

Abstract

In the past two decades, ionic liquids (ILs) have been acknowledged as potentially attractive “green” and “designer” solvents since their broader chemical space and the tunable nature of the diverse ions can finely modulate their physiochemical properties while enabling task-specific optimization. They have found numerous applications in fields ranging from enzymatic reactions to protein preservation, which focused on the development of various types of ILs and their application for providing protein stability in vitro. Among various families of ILs, some of them have serious limitations similar to organic solvents; they cause environmental toxicity as they are non-biodegradable. In other words, some of the ILs impart stress to biomolecules and ultimately denature the protein. In this regard, the need for biocompatible ILs has come to the light and cholinium-based ILs (Chn ILs) have proved themselves as the most promising ILs to support the structure of biomolecules. The family of Chn ILs has only taken growth in recent years. Despite the numerous studies, more exhaustive research in the field of Chn ILs and biomolecules still needs acceleration. Herein, we review the strategies and current progress on Chn ILs for protein and enzyme-based applications keeping in mind all crucial past and present research outcomes. Furthermore, we elucidate an overview of the various ways to enhance enzymatic activity, structural stability, and long-term storage of proteins in the presence of Chn ILs. We believe these insights will be fruitful for designing various processes based on ILs in the diverse field of biotechnology and ILs will serve as novel solvents for protein stability and enzymatic reactions, maintaining their utility in industrial and biomedical based applications. The huge varieties of biobased Chn ILs hold the promise of recent advances and developments for the correct selection of long-term storage of enzymes.

Fortification of thermal and structural stability of hemoglobin using choline chloride-based deep eutectic solvents

“…Both DESs were synthesized by using the standard protocol. 33,34 The process involved a hydrogen bond acceptor, [Ch]Cl, and a hydrogen bond donor, urea/Gly, as the starting materials. DES 1 was prepared by mixing [Ch]Cl and urea in a molar ratio of 1 : 2.…”

“…30 Moreover, tonnes of [Ch]Cl are produced annually to be used as an animal feed supplement, and therefore, it is not expensive. [31][32][33] The characteristics of [Ch]Cl-based DESs could be regulated by changing the type of HBD and the molar ratio of HBD to HBA. As HBDs, we have chosen Gly and urea.…”

Ion-Mediated Protein Stabilization on Nanoscopic Surfaces

“…67 Although there have been significant inroads in understanding protein−IL interactions, the question remains whether they can stabilize the protein−NP interface, which is critical for biomedicine and drug delivery formulations. 68,69 In this milieu, we have used choline cation-based ILs with two different anions as the negative counterparts. Choline was the preferred choice for the cationic counterpart of the IL, as it is biocompatible.…”

Studies on the Interaction between Model Proteins and Fluorinated Ionic Liquids

“…Although the interaction between proteins is essential for life, an abnormal increase in protein–protein interactions can lead to the unwanted formation of protein aggregates, which play major roles in diseases such as Alzheimer’s, type 2 diabetes, and spongiform encephalopathies [ 4 ]. This inherent structural and chemical instability, associated with short half-lives when subjected to physical and chemical stress, limits the use of proteins as therapeutic agents [ 5 ]. However, since proteins are stabilized by the equilibrium between intramolecular interactions and interactions with the solvent environment, the employment of biocompatible cosolvents can provide an alternative strategy to preserve their stability [ 5 ].…”

“…This inherent structural and chemical instability, associated with short half-lives when subjected to physical and chemical stress, limits the use of proteins as therapeutic agents [ 5 ]. However, since proteins are stabilized by the equilibrium between intramolecular interactions and interactions with the solvent environment, the employment of biocompatible cosolvents can provide an alternative strategy to preserve their stability [ 5 ].…”