Unraveling the Effects of Purine- and Pyrimidine-Based Ionic Liquids on G-Quadruplex

Formation of G-quadruplex (GQ) at the termini of the chromosomes found in cancer cells is known to inhibit telomere elongation and hence cell growth. As a consequence, GQ has been identified as a potential target for tumor-suppressing drugs. In recent times, aqueous ionic liquid (IL) solutions have been used as storage media for GQ samples. Hence, it is important and essential to obtain molecular-level insights into the interaction mechanism between GQ and IL components. In this work, we have performed molecular dynamics (MD) simulations of c-kit promoter GQ in aqueous solutions of nucleobase ionic liquids (NBILs) containing 1-ethyl-3-methylimidazolium (Emim⁺) cations in combination with purine-based adenine (Ade^-) and guanine (Gua^-) anions, and pyrimidine-based thymine (Thy^-) and uracil (Ura^-) anions. The calculations revealed contrasting effects of purine and pyrimidine-based ILs on the conformational flexibilities of the GQ. Importantly, greater influence of the pyrimidine-based ILs on the structural integrity of the GQ has been found to be associated with relatively higher propensity of the Emim⁺ cations to replace water molecules that are not directly bound at the GQ surface in the presence of Thy^- and Ura^- anions as compared to that in the presence of Ade^- and Gua^-. It is further observed that in addition to the negatively charged GQ backbone, the Emim⁺ cations also exhibit strong favorable interaction with the GQ nucleobases due to preferential parallel stacked arrangements between the cation imidazolium rings and the nucleobases. Our analyses suggest that aqueous IL solutions containing purine-based anions can act as good media for the preservation of GQs.