Design of azine antioxidants for sustainable biodiesel: integrating structural characterization and molecular modeling

The growing global demand for sustainable energy solutions has intensified the search for renewable alternatives to fossil fuels, with biodiesel emerging as a promising candidate due to its biodegradability and lower emissions. However, its large‐scale application is limited by low oxidative stability, which compromises storage and performance. In this study, three nitrobenzylidene azine derivatives (ACN1, ACN2, and ACN3) were synthesized and evaluated as potential antioxidant additives for biodiesel, integrating structural characterization, molecular modeling, and machine learning. Single‐crystal X‐ray diffraction revealed that the supramolecular organization was stabilized by weak intermolecular interactions, such as CH···O, OH···N, and π  π contacts, which influenced molecular packing and favored radical scavenging. Density functional theory calculations showed that substituent effects strongly modulated antioxidant behavior. ACN2 exhibited the lowest energy gap between the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO), whereas ACN1 demonstrated superior antioxidant potential due to its lower ionization potential and enhanced stabilization of radical intermediates. Fukui function and spin density analyses identified the azine R 1 R 2 C=N–N=CR 3 R 4 fragment as the key site for radical scavenging across the series. Machine learning models predicted that ACN1 would react with hydroxyl radicals at rates comparable with widely used commercial antioxidants such as butylated hydroxytoluene (BHT) and tert ‐butylhydroquinone (TBHQ). Toxicological assessments highlighted structure‐dependent safety profiles, with ACN3 showing a significantly higher LD 50 (2000 mg kg −1 ) in comparison with its counterparts, suggesting that it may be a safer candidate for industrial application. Overall, these findings confirm that azine derivatives are a promising and tunable class of additives for enhancing the oxidative stability of biodiesel.