Structural specificity of groove binding mechanism between imidazolium-based ionic liquids and DNA revealed by synchrotron-UV Resonance Raman spectroscopy and molecular dynamics simulations

The predicted capability of Ionic Liquids (ILs) in stabilizing the native structure of nucleic acids is relevant in biotechnology, especially for DNA storage and handling. In the present work, we implement a joint combination of advanced spectroscopic techniques such as synchrotron radiation-UV Resonance Raman spectroscopy (SR-UVRR) and molecular dynamics (MD) simulations for deepening insight into the sequence and structural specificity of the binding interactions between imidazolium-based ILs and both the phosphate groups and nucleobases in the minor and major grooves of double-stranded DNA. A 30-base pair double-stranded DNA structure has been chosen as a model of natural DNA. The experimental and simulation results give evidence of the predominance of a groove binding mechanism between ILs cations and DNA, with preferential interactions among guanine residues and the shorter alkyl-chain length on imidazolium cations. Raman experiments allowed us to detect both cooperative transition and reversible pre-melting structural transformations that involve specific tracts in the structure of DNA and are turned on at lower temperatures for guanine residues than for adenine ones. The more marked effect on the pre-melting states of adenine operated by the imidazolium-based ILs with chloride as anion suggests a selective strong interaction of this anion with the DNA's adenine-rich tracts. MD simulation results reveal the influence of ILs on the structural properties of DNA and provide more details about the solvation, interaction, stability and flexibility of DNA in the hydrated ILs. According to MD analyses, simultaneous electrostatic and hydrophobic interactions drive the shorter alkyl-chain length of imidazolium cations to have greater interplays with the DNA major groove. © 2021 Elsevier B.V. All rights reserved.