Exploration of the multiscale interaction mechanism between natural deep eutectic solvents and silybin by QC calculation and MD simulation

As a biologically active component extracted from milk thistle seed, silybin has many pharmacological functions. In this study, by means of quantum chemical calculation and molecular dynamics simulation, the multiscale interaction mechanism between silybin and natural deep eutectic solvents (NADES) during the extraction was explored. Two NADES exhibiting different extraction performance, ChCl/1,4-butanediol (ChCl/BDO) and betaine/1,4-butanediol (Bet/BDO) were investigated. Firstly, σ-profiles and RESP charges were analyzed for interpreting the polarity and hydrogen-bond forming potential of silybin and NADES. Then hydrogen bond between silybin and NADES was demonstrated by reduced density gradient. The interaction energy between ChCl/BDO-silybin was stronger than Bet/BDO-silybin. Additionally, the radial, combined and spatial distribution functions indicated a stronger interaction between Cl of ChCl and H29 of silybin than others, meanwhile, Silybin H29 was surrounded more by ChCl or Bet than BDO. Finally, the mean square displacement (MSD) revealed the higher self-diffusion coefficient of silybin in ChCl/BDO when compared with Bet/BDO-silybin system. In conclusion, Cl of ChCl exhibited dominant interaction with silybin when compared with BDO or Bet, which explained the better extraction performance of ChCl/BDO. This microscopic mechanism study facilitates a better design of novel solvent for silybin extraction, and provides a reference for the improvement of the extraction process for similar natural products.