Molecular mechanism for the interaction of natural products with ionic liquids: Insights from MD and DFT study

Ionic liquids (ILs) as a class of green sustainable solvents, have been widely studied and used for the extraction, separation, recovery, and catalytic conversion of natural products (NPs). It is well known that elucidating the dynamic interaction behavior and mechanism of NPs in ILs can help rationally design efficient IL solvent systems at the molecular level. However, the interaction mechanism of rutin molecules and ILs is still unclear. In this contribution, an exhaustive theoretical study of dynamic interaction behavior and mechanism of rutin in six imidazolium-based IL systems is presented for the first time by combining molecular dynamics (MD) simulations with density functional theory (DFT) calculations. Meanwhile, the synergistic effect of cation and anion on rutin-IL complexes stability is deeply investigated by the frontier molecular orbital (FMO), electrostatic potential (ESP), radial distribution functions (RDF), averaged non-covalent interaction (aNCI) and non-covalent interaction (NCI). The final result provides a comprehensive molecular mechanism of interaction between rutin and ILs. The combination of various nonbonded forces (such as H-bond, van der Waals, repulsion and cation-π stacking) between molecules determines the stability of rutin-IL complexes. In addition, the structure, size and functional groups of ILs play a decisive role in promoting the formation of nonbonded forces. Our work shows that avoiding substituents with steric hindrance and electron-withdrawing effect in anions, considering the symmetry of the alkyl chain of imidazolium cations, and enhancing the cooperation between anions and cations is a promising pathway to develop a new and efficient ILs solvent systems for the NPs extraction, recovery, separation, detection, and catalytic conversion.