Antioxidant activity of novel phenolic compounds bearing basic substituents—synthesis and insights from molecular modeling

Free radicals are important reactive species that perform both positive and negative functions within living organisms. Antioxidants play a significant part in preventing or managing diseases linked to oxidative stress, including cancer, cardiovascular disease, and neurodegenerative disorders. In the presented work, a two-step synthesis was used to prepare 15 phenolic compounds substituted with various N-heterocyclic moieties as potential antioxidants. The starting materials were 4-hydroxyphenylalkyl ketones, which were converted into 4-hydroxy-3-chloromethylphenylalkyl ketones via chloromethylation. These then reacted with various aliphatic amines (dimethylamine, diethylamine, isopropylamine, isobutylamine, and tertbutylamine) and heterocyclic amines (pyrrolidine, piperidine, morpholine, azepane, and 4-methylpiperazine). The purity of the products was confirmed by thin-layer chromatography, and their infrared (IR), ultraviolet (UV), and proton nuclear magnetic resonance (¹H NMR) spectra were measured. Their antioxidant activity was determined using the DPPA and ABTS methods. The ABTS results show antioxidant activity values ranging from 85% to 95%, which are higher than the values for oxygen derivatives. Conformational analysis revealed a stronger hydrogen bond between OH and N than between OH and O. In the case of the compound containing isobutyl, the formation of an intramolecular hydrogen bond (NH⋯O) is considered more likely.