Stabilizing native nucleic acid structures is critical for developing nucleic acid-based therapeutics, which have enormous potential in biomedicine for disease prevention, disease treatment and diagnostics. Imidazolium chloride ionic liquids (ImCl ILs) can increase the thermal stability of G-Quadruplex DNA structures. Generally, G-Quadruplex DNA requires K⁺ (or sometimes Na⁺) to stabilize their structures via coordination of the guanine bases. In this work we investigated the ability of ImCl ILs to stabilize G-Quadruplex DNA without K⁺ present. Temperature-dependent CD spectroscopy showed that the ImCl ILs that can form micelles in aqueous solution ([OMIM]Cl and [DMIM]Cl) increase the thermal stability of G-Quadruplex DNA without K⁺, while the ImCl ILs that do not form micelles ([EMIM]Cl, [BMIM]Cl, and [HMIM]Cl) do not stabilize the structure. Notably, [OMIM]Cl and [DMIM]Cl only stabilize G-Quadruplex DNA at concentrations above their CMC values; at concentrations equal to their CMC values these ILs actually destabilize the structure. MD simulations were performed to elucidate the mechanism of thermal stabilization. Simulations are consistent with experimental results as [DMIM]Cl micelles keep the G-Quadruplex structure stable without K⁺ present. These results show how ILs can encapsulate and stabilize DNA, which can help guide the development of new strategies for stabilizing DNA and RNA structures at room temperature.

Timothy Vaden

Professor, Rowan University

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