Hydroxyl Radical Scavenging of Indole-3-Carbinol: A Mechanistic and Kinetic Study

Indole-3-carbinol (I3C) is the product of the enzymatic hydrolysis of glucobrassicin in the human body. I3C exhibits diverse bioactivities. It is used as a supplement to enhance the efficiency of some cancer therapies and is available as an over-the-counter dietary supplement described as a potential antioxidant, among other health benefits. Thus, it is important to develop an in-depth understanding of its antioxidant activity. In this study, the hydroxyl radical scavenging of I3C has been investigated in silico under physiologically relevant conditions (aqueous and lipid-mimetic pentyl ethanoate environment) using thermochemical and kinetic calculations. For benchmarking purposes, the results were compared to known experimental data. The overall reaction rate constant of the HO^• radical scavenging of I3C in water was found to be 2.30 × 10¹⁰ M^-1 s^-1 and over two times lower in lipid-mimetic pentyl ethanoate solvent at 7.74 × 10⁹ M^-1 s^-1. The results also highlighted that the HO^• radical scavenging follows almost exclusively the radical adduct formation mechanism (>94%) in a lipid mimetic medium, whereas this mechanism contributes about 60% in aqueous environments. I3C is considered a dopamine-like antioxidant, its main function being prevention of oxidative degradation of lipids; our study supports this view.