The Nitro-Chloro Substitution on Two Quinolinone-Chalcones: From Molecular Modeling to Antioxidant Potential

Abstract

The increasing demand for renewable energy has driven the search for sustainable biodiesel additives whose molecular structures exhibit antioxidant potential. This study reports the synthesis and solid-state X-ray diffraction studies of two quinolinone-chalcone derivatives, C28H19N3O7S (QC-NO2) and C28H19ClN2O5S (QC-Cl). Density functional theory calculations and Fukui function analysis were combined with a predictive tool based on previously trained machine learning models to investigate the impact of nitro and chloro substituents on their physicochemical properties, molecular reactivity, and antioxidant potential. Theoretical results indicated that QC-Cl exhibits higher electronic stability, with larger energy gaps (599 kJ/mol) and greater nucleophilicity, while QC-NO2 shows enhanced electrophilicity and electron-accepting ability. Molecular electrostatic potential maps and Fukui functions highlighted reactive sites consistent with the substituent electronic effects, particularly the strong electron-withdrawing character of the nitro group. Predictions of the hydroxyl radical scavenging rate constant (kOH) obtained using a tool based machine learning models demonstrated that QC-NO2 (6.09 × 109 M–1·s–1) performs comparably to commercial antioxidants such as BHT and TBHQ. These findings underscore the relevance of structural modification in tuning antioxidant activity and suggest that chalcone-based hybrids, especially QC-NO2, are promising candidates to act as antioxidants in biodiesel.