Amine moieties play different roles as electron-donating groups on quinoline derivatives

Abstract Quinoline derivatives play a crucial role in antimalarial therapy, and their biological properties are highly dependent of their basicity, particularly at the amine groups. The Amine moieties significantly contribute to the antioxidant capacity of quinoline derivatives through electron transfer mechanisms. A theoretical study was conducted to investigate the structure-nucleophilicity and antioxidant capacity of quinoline derivatives, specifically chloroquine and quinine, through electron transfer using DFT/B3LYP/6-311++G(2d,2p) methods. The HOMO values were utilized to assess nucleophilicity, while the ionization potential was indicative of electron donating capacity. To explore different aspects of the molecules, three approaches were proposed: simplification, fragmentation, and modification on amine moieties. Our findings reveal a synergistic effect between 4-amino-quinoline and tertiary amine in quinoline derivatives, enhancing their overall antioxidant capacity. However, the presence of the chlorine atom decreases its contribution as an electron withdrawing group. Chloroquine exhibits a higher antioxidant capacity when compared to quinine, and their respective electron donation abilities are correlated with their pKa values. The synergistic effect between the 4-amino-quinoline and tertiary amine is particularly evident in chloroquine, surpassing the antioxidant capacity of 6-methoxy-4-methyl-quinoline moiety in quinine.