Scavenging Reactivity of N‐Protonated Histamine and Serotonin Toward Hydroperoxyl Radical in Aqueous Phase: A DFT Study

ABSTRACT Histamine and serotonin are predominantly protonated on aliphatic amine nitrogen under physiological conditions (pH = 7.4). Using density functional theory, we calculated various energetic and kinetic parameters to understand the scavenging reactivity of protonated histamine and serotonin towards the hydroperoxyl radical (•OOH) in the aqueous phase and compared the results with non‐protonated states. Activation energies for aromatic‐NH and phenolic‐OH of N‐protonated serotonin are very low, which are respectively ∼7.66 and ∼4.47 kcal mol −1 and predict the strong antioxidant activity of N‐protonated serotonin. Scavenging reactivity of histamine is lower than that of serotonin. However, both thermodynamic and kinetic parameters predicted that the scavenging activity of both histamine and serotonin in the N‐protonated state is comparatively lower than in the non‐protonated state. The scavenging time scales for aromatic‐NH and phenolic‐OH of serotonin in the protonated state are respectively ∼67 ns and <1 ns, whereas it is ∼1s for aromatic‐NH of N‐protonated histamine. The estimated time scales indicate that both aromatic‐NH and phenolic‐OH in N‐protonated histamine and serotonin can scavenge the •OOH radicals successfully within the lifetime of •OOH radicals (∼7s). All the observed results have been supported by complementary calculations such as NBO charges, ESP, FMO, SOMO, and SDD surfaces.