Beta‐Cyclodextrin Inclusion Complexes with Phenolic Synthetic Antioxidants: Synthesis, Spectroscopic Characterisation, Molecular Modeling, and Activity Efficiency

Abstract Butylated hydroxytoluene (BHT) and butylated hydroxyanisole (BHA) are synthetic phenolic antioxidants widely used as additives in the food industry. In this context, beta‐cyclodextrin (βCD) appears as a suitable encapsulating agent due to its bioavailability, water solubility, and high efficacy in incorporating phenolic compounds. The inclusion complexes (ICs) are prepared via the co‐precipitation method, followed by freeze‐drying. 1 H NMR and FTIR are used to confirm the formation of the ICs. Molecular modeling, including molecular docking and molecular dynamics (MD) simulations, is conducted to investigate the interactions involved in the ICs and their thermodynamic stability, respectively. Furthermore, the effect of the inclusion complexes on antioxidant efficacy is evaluated through the scavenging capacity of DPPH. The spectroscopic methods confirmed that BHT and BHA are successfully incorporated into βCD. Molecular docking revealed the formation of hydrogen bonds, with binding energies of −5.76 and −5.16 kcal mol −1 for BHT/βCD and BHA/βCD, respectively. After performing MD simulations for 100 ns, both ICs demonstrated a high degree of stability over time. The DPPH assay showed an increase in antioxidant ability for BHT (IC 50 decreased from 68.82 to 53.32 µg mL −1 ) but a decrease in efficiency for BHA (IC 50 increased from 451.25 to 598.36 µg mL −1 ).