Ionic liquids make DNA rigid

Persistence length of dsDNA is known to decrease with increase in ionic concentration of the solution. In contrast to this, here we show that persistence length of dsDNA increases dramatically as a function of ionic liquid (IL) concentration. Using all atomic explicit solvent molecular dynamics simulations and theoretical models we present, for the first time, a systematic study to determine the mechanical properties of dsDNA in various hydrated ionic liquids at different concentrations. We find that dsDNA in 50 wt% ILs have lower persistence length and stretch modulus in comparison to 80 wt% ILs. We further observe that both persistence length and stretch modulus of dsDNA increase as we increase the ILs concentration. Present trend of stretch modulus and persistence length of dsDNA with ILs concentration supports the predictions of the macroscopic elastic theory, in contrast to the behavior exhibited by dsDNA in monovalent salt. Our study further suggests the preferable ILs that can be used for maintaining DNA stability during long-term storage.Comment: 16 pages, 3 figures, Supplementary Information (Accepted for publication in the Journal of Chemical Physics, AIP (USA)

Dynamics of physiologically relevant noncanonical DNA structures: an overview from experimental and theoretical studies

DNA is a complex molecule with phenomenal inherent plasticity and the ability to form different hydrogen bonding patterns of varying stabilities. These properties enable DNA to attain a variety of structural and conformational polymorphic forms. Structurally, DNA can exist in single-stranded form or as higher-order structures, which include the canonical double helix as well as the noncanonical duplex, triplex and quadruplex species. Each of these structural forms in turn encompasses an ensemble of dynamically heterogeneous conformers depending on the sequence composition and environmental context. In vivo, the widely populated canonical B-DNA attains these noncanonical polymorphs during important cellular processes. While several investigations have focused on the structure of these noncanonical DNA, studying their dynamics has remained nontrivial. Here, we outline findings from some recent advanced experimental and molecular simulation techniques that have significantly contributed toward understanding the complex dynamics of physiologically relevant noncanonical forms of DNA

Nanostructural Reorganization Manifests in <i>Sui-Generis</i> Density Trend of Imidazolium Acetate/Water Binary Mixtures

Ionic liquids (ILs) are emerging as a novel class of solvents in chemical and biochemical research. Their range of applications further expands when a small quantity of water is added. Thus, the past decade has seen extensive research on IL/water binary mixtures. While the thermophysical properties of most of these mixtures exhibited the expected trend, few others have shown deviations from the general course. One such example is the increase in density of the 1-alkyl-3-methyl imidazolium acetate ([R_<i>n</i>mim]­[Ac])-based ILs with the addition of low to moderate concentrations of water. Although such a unique trend was observed for imidazolium cations of different tail lengths and also from independent experiments, the molecular basis of this unique behavior remains unknown. In this study, we examine the nanostructural reordering in [R_<i>n</i>mim]­[Ac] (<i>n</i> = 2–6) ILs due to added water by means of molecular dynamics simulations, and correlate the observed changes to the <i>sui-generis</i> density trend. Results suggest that the initial rise in density in these ILs mainly pertains to the water-induced increased spatial correlation among the polar components, where high basicity of the acetate anion plays a key role. At moderate water concentration, the density can rise further for ILs with longer cation tails due to hydrophobic clustering. Thus, while [emim]­[Ac]/water mixtures exhibit the density turnover at <i>X</i>_w = 0.5, [bmim]­[Ac] and [hmim]­[Ac] show the turnover at <i>X</i>_w = 0.7. The detailed understanding provided here could help the preparation of optimal IL/water binary mixtures for various biochemical applications

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

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

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

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

High Nucleobase-Solubilizing Ability of Low-Viscous Ionic Liquid/Water Mixtures: Measurements and Mechanism

Research on nucleobases has always been on the forefront owing to their ever-increasing demand in the pharmaceutical, agricultural, and other industries. The applications, however, became limited due to their poor solubility in water. Recently, ionic liquids (ILs) have emerged as promising solvents for nucleobase dissolution, as they exhibit >100-fold increased solubility compared to water. But the high viscosity of ILs remains as a bottleneck in the field. Here, by solubility and viscosity measurements, we show that addition of low-to-moderate quantity of water preserves the high solubilizing capacity of ILs, while reducing the viscosity of the solution by several folds. To understand the mechanism of nucleobase dissolution, molecular dynamics simulations were carried out, which showed that at low concentrations water incorporates into the IL–nucleobase network without much perturbing of the nucleobase–IL interactions. At higher concentrations, increasing numbers of IL anion–water hydrogen bonds replace IL–nucleobase interactions, which have been confirmed by ¹H- and ¹³C NMR chemical shifts of the IL ions