Theoretical studies on the quercetin interactions in the oil-in-water F127 microemulsion: A DFT and MD investigation

Quercetin (Q) has attracted the attention of researchers for potential applications in advanced therapeutic treatments due to its antioxidant attributes and renal tissue improvement. F127-based oil-in-water microemulsions improved the bioavailability of Q and showed greater retention and more stable release. In this study, Q-loaded microemulsion was designed with the help of simulation techniques. The mechanism of action of Q was investigated in the bulk and microemulsion forms. The simulation results show the fast accumulation of Q molecules around 2,2-diphenyl-1-picrylhydrazyl (DPPH) molecules (free radicals) in bulk form and the slow accumulation of Q molecules around DPPH in microemulsion form. The stable release of Q in microemulsion form was found to be due to the powerful van der Waals (vdW) interactions between Q and F127. For a better and deeper understanding of the nature of mutual interactions between Q (enol and keto forms) and F127, quantum mechanical calculations were performed at the B3LYP/6-31G(d,p) level of theory. In particular, atoms in molecules (AIM) and natural bond orbital (NBO) analyses were performed to evaluate the strength of the interactions between Q and F127. The results showed that the formation of a strong hydrogen bond (HB) between Qenol and F127 stabilizes the microemulsion system and can contribute to the better performance of Q microemulsion compared to free Q in bulk.