Stability of DNA in Hydrated Ionic Liquids: Effect of Solvent Nanostructuring

Abstract

Recently, hydrated ionic liquids (ILs) have been identified as novel solvent media in conferring greater stability on proteins and DNA. In an earlier study with a conventional imidazolium-based IL, we established intrusion of the IL cation into the solvation shell of DNA, particularly the minor groove, as a key factor in long-term stability. Nonetheless, there is a continuous surge to find and develop nontoxic ILs for biological applications. Thus, we extended our investigations to DNA stability in biocompatible hydrated choline-based ILs with a range of anions. Results from molecular dynamics simulations and CD spectroscopic data suggest that the native B-conformation of DNA is retained in these ILs. DNA stability is majorly attributable to IL cation-DNA interactions, and for a given anion, the imidazolium cation shows stronger binding to DNA than cholinium. The extent of DNA dehydration by these diverse classes of ILs is, however, comparable. The solvent microstructure revealed strong ion pairing in ILs composed of the cholinium cation and carboxylate anions. ILs of such kind, by virtue of their larger volume compared to ILs with solvent-separated ion-pairs, can dehydrate DNA effectively, despite being weakly binding ligands. Conversely, the imidazolium cations dehydrate by integrating into the DNA grooves through strong electrostatic and hydrogen bonding interactions, closely resembling groove binding drugs. The implications of this differential mode of dehydration, and consequent stability, of DNA by the two classes of ILs are expected to find relevance in different areas of DNA-IL-based applications.