Chirality-dependent interaction between zein and dihydromyricetin isomers: binding mechanism and gastrointestinal...

Stereoisomerism, referring to the existence of molecules as chiral forms with distinct three-dimensional configurations, plays a crucial role in determining how bioactive compounds interact with food proteins. This study investigated the effects of dihydromyricetin (DMY) stereochemistry, including (2R, 3R)-, (2S, 3S)-, and racemic (rac)- forms, on its binding with zein and the subsequent release during simulated digestion. Zein-DMY complexes were prepared and analysed using fluorescence spectroscopy, molecular dynamics simulation, and an in vitro gastrointestinal model. Results showed that all zein-DMY complexes exhibited smaller particle size and higher zeta potential than original zein (p < 0.05). Fluorescence quenching analysis suggested that zein-(2R, 3R)-DMY complex had higher quenching constants (3.2 × 10⁴ L·mol^-1) and binding constants (3.2 × 10⁴ L·mol^-1) than the zein-(2S, 3S) and zein-(rac)-DMY complexes. Molecular dynamics simulations further confirmed this preferential binding, showing a lower average root-mean-square deviation (RMSD, 0.26 nm) and a more negative binding energy (-38.2 kcal/mol) of zein-(2R, 3R)-DMY interaction compared to zein-(2S, 3S)-DMY interaction. In vitro digestion results revealed that zein-(2R, 3R)-DMY complex had the lowest cumulative release of DMY in the intestinal phase. The digestive products of the zein-DMY complexes, particularly zein-(2R, 3R)-DMY, exhibited significantly enhanced antioxidant potency compared to pure DMY (p < 0.05). In conclusion, the chiral configuration of DMY is the main factor determining its interaction with zein and its digestive release behaviour, providing valuable insights for designing stable, protein-based delivery systems in functional food applications.