Decoding the new dimensions of leucodelphinidin as a dual antioxidant and anti-diabetic candidate: A DFT, docking and...

Leucodelphinidin (LDN) is an underrated flavonoid with dual roles as a potent antioxidant and anti-diabetic agent. This study evaluates its radical scavenging ability using density functional theory (DFT) across multiple antioxidant pathways. This includes hydrogen atom transfer (HAT), sequential electron transfer-proton transfer (SET-PT) and sequential proton loss electron transfer (SPLET) extending from single to hepta mechanisms. Antioxidant efficiency is confirmed through bond dissociation enthalpy (BDE), electron transfer enthalpy (ETE), proton affinity (PA), electron affinity (EA), proton dissociation enthalpy (PDE) and ionization potential (IP) parameters. Molecular electrostatic potential (MEP) mapping and frontier molecular orbital (FMO) analyses spotted the electron rich regions prone to radical attack, while the time dependent DFT (TD-DFT) revealed key electronic transitions. Further insight into mechanistic behavior is obtained through atoms in molecule (AIM) analysis, global reactivity descriptors and non-covalent interaction - reduced density gradient (NCI-RDG) investigation. For the biological validation, LDN is docked with human glucokinase and pancreatic α-amylase and the outcomes are subjected to molecular dynamics (MD) simulations. This computational investigation integrates the multi-pathway radical scavenging evaluations along with enzyme docking and dynamics simulations, unveiling the mechanisms that couple the oxidative stress modulation with glucose regulation emphasizing LDN's capability as a therapeutic lead for oxidative stress related metabolic disorders.