Dual Antioxidant / Pro-Oxidant Behavior of the Tryptophan Metabolite 3-Hydroxyanthranilic Acid: A Theoretical Investigation on Reaction Mechanisms and Kinetics
The antioxidant and pro-oxidant behavior of 3-hydroxyanthranilic acid was investigated using Density Functional Theory. In the absence of metal ions 3-hydroxyanthranilic acid would act as an excellent antioxidant by scavenging free radicals. It was found to be an excellent peroxyl radical scavenger in both lipid and aqueous solution, reacting with •OOH faster than Trolox. Moreover, the gathered kinetic data supports the idea that 3-hydroxyanthranilic acid significantly contributes to the antioxidant activity usually attributed to tryptophan. On the contrary, in the presence of metal ions (at physiological pH) it would exhibit pro-oxidant behavior. This behavior arises from the Cu(II) reducing ability of the anionic fractions of this compound, which would contribute to produce Cu(I) and consequently promote •OH production via the Fenton reaction. Accordingly, the environmental factor identified as crucial for ruling the dual behavior of 3-hydroxyanthranilic acid is the presence of metal ions. In addition, the pH is also predicted to influence the pro-oxidant effects of this compound.