Detailed Investigation of the Outstanding Peroxyl Radical Scavenging Activity of Two Novel Amino-Pyridinol-Based Compounds

The ability of two novel amino-pyridinol based compounds (NPyr6 and NPyr7) as peroxyl radical scavengers was investigated in silico. The gathered data indicate that they are exceptionally efficient in that role. However, solvent polarity influences their relative efficiency for that purpose. NPyr6 was identified as the best peroxyl radical scavenger in lipid solution, while NPyr7 takes that place in aqueous solution. Both compounds present two acid-base equilibria, which influence their reactivity in aqueous solution. The associated pKa values were estimated. Several reaction mechanisms were explored. Hydrogen transfer from the phenolic group was identified as the chemical route with the highest contribution to the antioxidant behavior of the investigated compounds in both, nonpolar medium and aqueous solution (at 2 ≤ pH ≤ 10). At higher pH other reaction pathways become the most relevant ones. In addition, their bioavailability, cell permeability, safety, and manufacturability were evaluated. According to these, particularly toxicity, NPyr7 seems to be a better candidate for use as an oral drug to fight oxidative stress than NPyr6.