Fluorescence and Molecular Simulation Studies on the Interaction between Imidazolium-Based Ionic Liquids and Calf Thymus DNA

Abstract

This work presents a molecular level investigation on the nature and mode of binding between imidazolium-based ionic liquids (ILs) ([C n bim]Br where n = 2, 4, 6) with calf thymus DNA. This investigation offers valuable insight into the mechanisms of interactions that can affect the structural features of DNA and possibly cause the alteration or inhibition of DNA function. To expedite analysis, the study resorted to using molecular docking and COnductor like Screening MOdel for Real Solvents (COSMO-RS) in conjunction with fluorescence spectroscopic data for confirmation and validation of computational results. Both the fluorescence and docking studies consistently revealed a weak interaction between the two molecules, which corresponded to the binding energy of a stable docking conformation in the range of −5.19 to −7.75 kcal mol −1 . As predicted, the rod-like structure of imidazolium-based ILs prefers to bind to the double-helix DNA through a minor groove. Interestingly, the occurrence of T-shape π-π stacking was observed between the amine group in adenine that faces the aromatic ring of imidazole. In addition, data of COSMO-RS for the interaction of individual nucleic acid bases to imidazolium-based ILs affirmed that ILs showed a propensity to bind to different bases, the highest being guanine followed by cytosine, thymine, uracil, and adenine. software, K.J.; validation, N.M.Y., H.A., and R.A.W.; formal analysis, K.J. and M.A.K.; investigation, N.M.Y., H.A., and R.A.W.; resources, K.J.; writing-original draft preparation, K.J. and M.A.K.; writing-review and editing, H.A., M.B.A.R., and R.A.W.; visualization, K.J., M.A.K., and N.M.Y.; supervision, M.B.A.R., H.A., and R.A.W.; funding acquisition, K.J. All authors have read and agreed to the published version of the manuscript.

Exploring the Interactions of Ionic Liquids with Bio-Organic Amphiphiles Using Computational Approaches

“…The split enthalpy contributions also indicate that hydrogen bonds were predicted to be the dominant contribution to the favorability of MG mixing in ILs, followed by electrostatic interaction and with minimal contribution from van der Waals interactions (Figure b). This same pattern has been seen with interactions between other biomolecules at 298.1 K. For example, the binding of imidazolium ILs to double-helix DNA was found to have a negative excess enthalpy driven mainly by hydrogen-bonding and misfit interactions . Keratin dissolution by a large range of imidazolium- and choline-based ILs also showed significant hydrogen-bonding interactions contributing to negative excess enthalpies of mixing .…”

“…This same pattern has been seen with interactions between other biomolecules at 298.1 K. For example, the binding of imidazolium ILs to double-helix DNA was found to have a negative excess enthalpy driven mainly by hydrogen-bonding and misfit interactions. 49 Keratin dissolution by a large range of imidazolium-and choline-based ILs also showed significant hydrogen-bonding interactions contributing to negative excess enthalpies of mixing. 10 Hydrogen bonds have also been predicted more broadly to be a unique force that facilitates IL−IL aggregates and plays a large role in the reactivity of IL systems.…”

Assessing the Suitability of a Dicationic Ionic Liquid as a Stabilizing Material for the Storage of DNA in Aqueous Medium

“…The longer alkyl chain-containing IL system is expected to induce more hydrophobic interactions with DNA, resulting in more exclusion of EB out of the DNA microenvironment. 41 Interestingly, despite the fact that both DIL and MIL2 contain the same alkyl chain, the lower fluorescence quenching in the presence of DIL than that in the presence of MIL2 clearly indicates the role of the extra pyrrolidinium ring head of DIL in the DNA−IL interaction process. These observations also indicate that DIL has a different interaction pattern with DNA than that is usually observed for DNA−MIL interactions.…”

“…The relatively higher fluorescence quenching by MIL2 than that by MIL1 may have occurred due to the presence of a longer alkyl chain (eight −CH 2 ) in the former IL system. The longer alkyl chain-containing IL system is expected to induce more hydrophobic interactions with DNA, resulting in more exclusion of EB out of the DNA microenvironment . Interestingly, despite the fact that both DIL and MIL2 contain the same alkyl chain, the lower fluorescence quenching in the presence of DIL than that in the presence of MIL2 clearly indicates the role of the extra pyrrolidinium ring head of DIL in the DNA–IL interaction process.…”

New insights on the effects of ionic liquid structural changes at the gene expression level: Molecular mechanisms of toxicity in Daphnia magna

“…which may be a response to ROS insult or to direct impact as ILs can enter the cell nucleus and directly damage the DNA [38,74,85]. Programmed cell death occurring as a response to the three ILs is suggested by the overall up-regulation of apoptosis-related genes [86], e.g.…”