Dynamically Heterogeneous Solvation Environment around a G-Quadruplex in Aqueous Solutions Containing Nucleobase Ionic Liquids

Abstract G-quadruplexes (GQs) are guanine-rich non-canonical nucleic acid structures that play crucial roles in different biological processes. Their structures and functions are highly dependent on the organization and dynamics of the surrounding solvent environment. Ionic liquids (ILs) act as excellent media for storing GQs by modifying their hydration patterns and dynamics. However, systematic studies on the solvation behavior of GQs remain scarce. Attempts have been made in this study to explore how aqueous solutions containing nucleobase (purine and pyrimidine) ionic liquids (NBILs) alter the time scale of dynamic heterogeneity within the GQ solvation shell. The calculations revealed that the solvent (water) and the cosolvent (NBIL) have markedly nonuniform spatial density distributions around the GQ, with the cations and anions exhibiting more heterogeneous distributions than water due to their stronger and more specific interactions with the GQ. It is found that the GQ can trap water within its confined pockets, thereby leading to nonuniform water residence times around it. Our analyses demonstrated that both water and IL around the GQ exhibit highly retarded heterogeneous translational and rotational motions. Among the two components, water molecules experience a comparatively greater degree of restriction in mobility due to their wide range of interaction strengths and the excluded-volume effect of the GQ. Interestingly, the relative increase in dynamic heterogeneity at the GQ interface in aqueous medium with respect to pure bulk water has been found to be noticeably greater as compared to the corresponding increase in dynamic heterogeneity at the interface in aqueous NBIL solutions with respect to their respective bulk states. Further, heterogeneity in translational motions of solvent components has been found to be much higher in purine-based IL solutions than in pyrimidine-based ones, though no such effect was observed for the rotational motions of the solvent components.