Groove Binding Mechanism of Ionic Liquids: A Key Factor in Long-Term Stability of DNA in Hydrated Ionic Liquids?

Abstract

Nucleic acid sample storage is of paramount importance in biotechnology and forensic sciences. Very recently, hydrated ionic liquids (ILs) have been identified as ideal media for long-term DNA storage. Hence, understanding the binding characteristics and molecular mechanism of interactions of ILs with DNA is of both practical and fundamental interest. Here, we employ molecular dynamics simulations and spectroscopic experiments to unravel the key factors that stabilize DNA in hydrated ILs. Both simulation and experimental results show that DNA maintains the native B-conformation in ILs. Simulation results further suggest that, apart from the electrostatic association of IL cations with the DNA backbone, groove binding of IL cations through hydrophobic and polar interactions contributes significantly to DNA stability. Circular dichroism spectral measurements and fluorescent dye displacement assay confirm the intrusion of IL molecules into the DNA minor groove. Very interestingly, the IL ions were seen to disrupt the water cage around DNA, including the spine of hydration in the minor groove. This partial dehydration by ILs likely prevents the hydrolytic reactions that denature DNA and helps stabilize DNA for the long term. The detailed understanding of IL-DNA interactions provided here could guide the future development of novel ILs, specific for nucleic acid solutes.

Thermodynamics of site-specific small molecular ion interactions with DNA duplex: a molecular dynamics study

“…This is consistent with the earlier experimental findings by Falsenfeld et al [17]. Chandran et al used a combination of molecular dynamics simulations and techniques such as circular dichroism, UV-visible spectroscopy and fluorescent dye displacement assay to demonstrate that hydrated ionic liquid cations can penetrate the DNA grooves and influence its thermodynamic stability via hydrophobic effects and electrostatic interactions [18]. Effect of varying TMA + concentrations on the thermostability of different DNA sequence was observed by Riccelli et al [19].…”

Identification of single nucleotides in MoS2 nanopores

“…3). A slight increase in noise is observed during the translocation, which can be explained by the fact that DNA interacts strongly with BmimPF 6 via electrostatic interaction between the cationic Bmim + groups and the DNA phosphates (P-O bonds) 33 . Because of this electrostatic interaction and the hydrophobic association between Bmim + and bases, DNA molecules can act as carriers for Bmim + ions from the cis to the trans chamber.…”

“…Although the current drop for dAMP is slightly larger than that for dTMP (0.65 nA, compared with 0.45 nA), we believe that this inconsistency might be due to the stronger Bmim + affinity towards dAMP compared with dTMP 40 . It has been established that RTILs can selectively bind to DNA 33 , and that RTILs based on metal chelate anions could be designed to have specific bonding to the bases 41 . In our system, this could be further exploited to amplify the small differences between the bases.…”

Interaction studies of cholinium-based ionic liquids with calf thymus DNA: Spectrophotometric and computational methods

“…Combining these two, several articles have been published describing the interaction of DNA with imidazolium, morpholinium, etc. based ILs [21][22][23][24][25][26][27][28][29]. For example, Liu and co-workers studied the impact of alkyl chain length present on imidazolium-based ILs [23] towards ct-DNA through extensive photophysical methods.…”