Substituent effects on antioxidant activity of monosubstituted indole-3-carbinols: A DFT study

Abstract

Indole-3-carbinol (I3C) is an indole compound with proven health benefits and thus potential preventive medicine and therapeutic applications. Here the origins of the substituent effects on the antioxidant activity of monosubstituted indole-3-carbinols (I3Cs) were studied in silico by calculating their thermochemical properties using the (RO)B3LYP/6-311++G(2df,2p)//B3LYP/6-311G(d,p) model chemistry. It was found that the electron withdrawing groups such as CF3, CN, COOH, COOMe can increase the bond dissociation energy (BDE) values of N-H bonds and decrease the BDE(C8-H) values, while the presence of the Br, Cl, F, Me, NMe2, NH2, NHMe, OH, OMe, Ph groups seems to decline the BDE(X-H)s (X = N, C). It is worth noticing that a sequential electron transfer mechanism is responsible for these I3Cs with the strong electron donating groups including NMe2, NHMe and NH2, while a hydrogen atom transfer mechanism is likely favored for the remaining monosubstituted I3Cs. The kinetic study according to the HAT mechanism showed that the CH3OO• radical scavenging of 2-NMe2-I3C derivative has the highest rate constant (k = 1.93×1010 M-1s-1) and it is higher than that of typical antioxidants i.e. Trolox or ascorbic acid. Thus, the results appear to suggest that the N-Br-I3C and 2-NMe2-I3C compounds are potential antioxidants.