Unveiling the Anti-Radical Potential of Galangin — A Detailed Density Functional Theory Investigation

A comprehensive quantum mechanical investigation into the antiradical activity of galangin (Glg), a natural flavonoid recognized for its robust antioxidant and anti-inflammatory properties, is presented. The compound undergoes successive deprotonation at C7 (pKa=7.48), C3 (pKa=9.34), and C5 (pKa=12.07). At pH 7.4, the predominant species are the neutral form (54.37%) and the first deprotonation product (45.11%), with the dianion present at a minor level (0.51%). According to eH-DAMA results, Glg exhibits improved antiradical effectiveness in water compared to apolar solvents. In both solvents, exergonic pathways towards •OOH radicals involve radical adduct formation at C2, while the highest propensity for HAT is associated with the C3 hydroxyl. Electron transfer pathways are not preferred, as indicated by Marcus’s parabola. The overall reaction rate was established at 3.77 × 103 M-1 s-1 in pentyl ethanoate and 1.69 × 105 M-1 s-1 in water, considering the molar fractions of individual species and hy-droperoxyl radicals at pH=7.4. The magnitude of the same reaction rate within the physiological pH range (pH=1.5 – 8.5) is consistently not less than 3.5, gradually reaching a peak value of 5.48 starting from pH=5. Furthermore, all Glg species readily undergo regeneration mediated by O2•-.