Radical Scavenging Activity of Natural-Based Cassaine Diterpenoid Amides and Amines.

The radical scavenging capacities of four new cassaine diterpenoid amides including 3β-hydroxydinorerythrosuamide (1), 3β-acetoxydinorerythrosuamide (2), 3β-tigloyloxydinorerythrosuamide (3), and 6α-hydroxydinorcassamide (4) present in leaf extract and four new cassaine diterpenoid amines namely erythroformine A (5), erythroformine B (6), 6α-hydroxy-nor-cassamine (7), and nor-erythrosuamine (8) recently identified in the extract of the bark of Erythrophleum fordii were elucidated using density functional theory (DFT) method. Different thermochemical properties characterizing antioxidant potential including bond dissociation enthalpy (BDE), proton affinity (PA), and adiabatic ionization potential (IP) were calculated at the B3LYP/6-311G(d,p) level of theory. Scavenging reaction mechanisms of cassaine diterpenes toward HOO• radical including formal hydrogen transfer (FHT; either hydrogen atom transfer (HAT) or proton coupled electron transfer (PCET)), radical adduct formation (RAF), single electron transfer (SET), and proton transfer (PT) were studied in the gas phase, water, and benzene. The potential energy profiles and kinetic calculations for the FHT and RAF reactions were calculated at 298.15 K. The results showed that all the studied compounds present strong antioxidant activity via HAT mechanism with BDEs varying from 69.4 to 77.9 kcal/mol. While solvents have only a slight effect on HAT and RAF mechanisms, SET and PT reactions are likely to occur in polar media. Among the studied compounds, 3 is the most reactive one both for HAT (H-abstraction at C7, Δ H -11.3 kcal/mol) and for RAF (radical addition at C13 = C15 bond, Δ H -5.2 kcal/mol) reactions. The rate constants of these reactions are also comparable with several referenced antioxidants such as Trolox and ascorbic acid.