Antioxidant Activity of the Pyridoindole Stobadine. Pulse Radiolytic Characterization of One-Electron-Oxidized Stobadine and Quenching of Singlet Molecular Oxygen

Abstract

Antioxidant properties of stobadine, a pyridoindole derivative described to exhibit cardioprotective properties, were characterized. The radical scavenging potential of stobadine was evaluated using pulse radiolysis with optical detection, by which it is shown that one-electron oxidation of stobadine with radicals such as C6H5O•, CCl3O2•, Br2•-, and HO• (reaction rate constants ≈5 × 108-1010 M-1 s-1) leads to the radical cation (absorbance maxima at 280 and 445 nm) which deprotonates from the indolic nitrogen (pKa = 5.0) to give a nitrogen-centered radical (absorbance maxima at 275, 335, and 410 nm), probably bearing a positive charge at the pyrido nitrogen. The radical of stobadine reacts with Trolox (i.e., 6-hydroxy-2,5,7,8-tetramethylchromane- 2-carboxylic acid) with a rate constant of 1.2 × 107 M-1 s-1 at pH 7.0 by one-electron oxidation to yield the phenoxyl-type radical of Trolox. This reaction is reversible (k = 2 × 105 M-1 s-1). The redox potential of stobadine at pH 7 is 0.58 V/NHE. Stobadine is also a quencher of singlet molecular oxygen (1O2) with an overall quenching rate constant of 1.3 × 108 M-1 s-1, determined with the endoperoxide of 3,3′- (1,4-naphthylene)dipropionate (NDPO2) as 1O2 source and by monitoring 1O2 photoemission with a germanium diode. © 1992, American Chemical Society. All rights reserved.