Antioxidant and free radical scavenging potential of feruloyl amino acids and dipeptide derivatives: an experimental and theoretical investigation.

Feruloyl amino acids and their corresponding dipeptide derivatives, obtained via condensation of ferulic acid-a well-established natural antioxidant-with amino acids and dipeptide moieties, represent a class of compounds with notable biological potential. In the present study, the antioxidant activity and radical-scavenging potential of a series of twelve feruloyl amino acid and dipeptide derivatives were systematically investigated using both in vitro assays and computational methods. Experimental evaluation was performed using DPPH˙ and ABTS˙+ assays. In the DPPH˙ assay, several derivatives exhibited EC50 values lower than those of the reference antioxidants BHA and BHT, whereas in the ABTS˙+ assay, all synthesized compounds displayed EC50 values below 1 µg mL-1, markedly outperforming both reference antioxidants. Quantum chemical calculations further supported these findings by elucidating the mechanisms underlying their antioxidant properties. Thermodynamic and kinetic analyses of hydroperoxyl (HOO˙) radical scavenging under simulation of aqueous conditions representative of a physiological environment demonstrated highly favorable reaction pathways, as well as significant metal-chelation capacity. Both feruloyl amino acids and their dipeptide derivatives showed high radical-scavenging activity in aqueous media, primarily via the single-electron transfer (SET) mechanism, with rate constants on the order of 106 to 107 M-1 s-1. In addition, these compounds demonstrated strong chelation ability toward Cu(ii) ions, predominantly through a bidentate coordination mode. These findings indicate that feruloyl amino acids and their dipeptide derivatives are potent antioxidants with potential therapeutic relevance.