ABSTRACT
Indolinonic hydroxylamine (IH) is known as a potential artificial antioxidant in apolar environments. Here, a library of 108 monosubstituted derivatives was screened in silico to identify a lead compound for increased antioxidant activity, following a strategy of shortlisting based on thermochemical and kinetic properties. It was found that the presence of substituents at the 2, 4, and 7 positions increased, while substituents in other positions decreased the BDE(O-H) values, in good correlation to the electron-donating ability of substituents. Among the studied compounds, the N and 5 amine-substituted derivatives have the lowest BDE(O-H) values (62.4-64.0 kcal mol-1). The presence of the strong electron-withdrawing substituents can decrease the proton affinities of the derivatives, whereas the decrease of ionization energies correlates to the electron-donating ability of the substituents. It was also found that the formal hydrogen transfer (FHT) mechanism is the favored pathway for the HOO· radical scavenging. Kinetic calculations showed that the rate constant of the reaction between N-NHMe-IH compound and HOO· radical following the FHT mechanism (k = 3.00 × 107 M-1 s-1) is about 8223 and 5253 times higher than those of Trolox and ascorbic acid, respectively, in the pentyl ethanoate solvent. Thus, N-NHMe-IH is expected to be the most powerful antioxidant reported to date in lipid environments.
