Use of Ionic Liquids in Protein and DNA Chemistry

Abstract

Ionic liquids (ILs) have been receiving much attention as solvents in various areas of biochemistry because of their various beneficial properties over the volatile solvents and ILs availability in myriad variants (perhaps as many as 10⁸) owing to the possibility of paring one cation with several anions and vice-versa as well as formulations as zwitterions. Their potential as solvents lies in their tendency to offer both directional and non-directional forces toward a solute molecule. Because of these forces, ionic liquids easily undergo intermolecular interactions with a range of polar/non-polar solutes, including biomolecules such as proteins and DNA. The interaction of genomic species in aqueous/non-aqueous states assists in unraveling their structure and functioning, which have implications in various biomedical applications. The charge density of ionic liquids renders them hydrophilic and hydrophobic, which retain intact over long-range of temperatures. Their ability in stabilizing or destabilizing the 3D-structure of a protein or the double-helical structure of DNA has been assessed superior to the water and volatile organic solvents. The aptitude of an ion in influencing the structure and stability of a native protein depends on their ranking in the Hofmeister series. However, at several instances, a reverse Hofmeister ordering of ions and specific ion-solute interaction has been observed. The capability of an ionic liquid in terms of the tendency to promote the coiling/uncoiling of DNA structure is noted to rely on the basicity, electrostatic interaction, and hydrophobicity of the ionic liquid in question. Any change in the DNA's double-helical structure reflects a change in its melting temperature (T _m), compared to a standard buffer solution. These changes in DNA structure have implications in biosensor design and targeted drug-delivery in biomedical applications. In the current review, we have attempted to highlight various aspects of ionic liquids that influence the structure and properties of proteins and DNA. In short, the review will address the issues related to the origin and strength of intermolecular interactions, the effect of structural components, their nature, and the influence of temperature, pH, and additives on them.

Keywords: DNA; Hofmeister series; circular dichroism; double-helical structure; intermolecular interaction; ionic liquid (IL); protein; salting phenomenon.

Figure 1

Interactions of a typical ionic liquids with proteins and DNA. Images in the backgroud are taken from the google.

Figure 2

Transition temperatures T_m for the thermal denaturation of RNase A as a function of the concentration c of added ILs with (A) Br⁻ and (B) Cl⁻ as a common anion. Reprinted with permission from Constantinescu et al. (2007).

Figure 3

Transition temperature T_m for the thermal denaturation of RNase A as a function of the concentration c of added ILs with [emim]⁺ as a common cation. Reprinted with permission from Constantinescu et al. (2007).

Figure 4

(A–D) Enthalpy–entropy compensation plots. The different segments correspond to different contributions of ΔΔG_u, ΔΔH_u, and TΔΔS_u. The blue diagonal corresponds to a complete enthalpy–entropy compensation. Data points correspond to different concentrations of the respective cosolute. (A,C,D) The first or the first two data points (≤ 0.5 M) of some compounds are omitted for clarity. Adopted from Senske et al. (2016).