A Continuous Visible Light Spectrophotometric Approach To Accurately Determine the Reactivity of Radical-Trapping Antioxidants

Abstract

Inhibited autoxidations-monitored either by O2 consumption or hydroperoxide formation-are the most reliable way to obtain kinetic and stoichiometric information on the activity of radical-trapping antioxidants (RTAs). While many comparatively simple "antioxidant assays" (e.g., the DPPH assay) have supplanted these in popularity, they are generally very poor substitutes since they often do not employ peroxyl radicals as the oxidant and do not account for both the kinetics and stoichiometry of the radical-trapping reaction(s). In an effort to make inhibited autoxidations as simple as the most popular "antioxidant assays", we have developed a spectrophotometric approach for monitoring reaction progress in inhibited autoxidations. The approach employs easily prepared 1-phenylbutadiene-conjugated or styrene-conjugated BODIPY chromophores (PBD-BODIPY or STY-BODIPY, respectively) as signal carriers that co-autoxidize along with a hydrocarbon substrate. We show that inhibition rate constants (kinh) are accurately determined for a range of phenolic and diarylamine RTAs using this approach and that mechanistic experiments, such as kinetic isotope effects and kinetic solvent effects, are equally easily carried out. Moreover, synergistic interactions between RTAs, as well as the unconventional activity of diarylamine RTAs, are captured using this methodology. Lastly, we show that the approach can be employed for monitoring reactions in aqueous solution.

Polysulfide-1-oxides react with peroxyl radicals as quickly as hindered phenolic antioxidants and do so by a surprising concerted homolytic substitution

“…These less oxidizable substrates generally provide greater resolution between inhibited and uninhibited phases of the autoxidation. 26 The results are shown for t -BuS(O)SS t -Bu and BnS(O)SSBn in Fig. 1C and D, respectively.…”

“…Although autoxidations are conventionally monitored by O 2 consumption, the recently developed method based on the competitive autoxidation of either PBD-BODIPY (with styrene) or STY-BODIPY (with cumene) was instead employed (Scheme 3). 26 Representative results are shown in Fig. 1A and B for varying amounts of BnS(O)SSBn and t -BuS(O)SS t -Bu.…”

On the Mechanism of Cytoprotection by Ferrostatin-1 and Liproxstatin-1 and the Role of Lipid Peroxidation in Ferroptotic Cell Death

“…36 Styrene is present in order to maintain a radical chain reaction, ensuring a steady-state concentration of peroxyl radicals and enabling derivation of the rate constant for the reaction of the added RTA with peroxyl radicals ( k inh ) from the initial rate of the inhibited reaction (Figure 1B). 36 The stoichiometry ( n ) of the RTA–peroxyl reaction is determined from the duration of the inhibited period ( t inh , also in Figure 1B). 36 …”

“…36 The stoichiometry ( n ) of the RTA–peroxyl reaction is determined from the duration of the inhibited period ( t inh , also in Figure 1B). 36 …”

“…Reaction progress was followed by the competitive oxidation of STY-BODIPY (Figure 3), the more slowly oxidized analogue of PBD-BODIPY wherein the 1-phenylbutadienyl moiety is replaced with a styryl moiety. 36 STY-BODIPY has been determined to react with peroxyl radicals with k p = 894 M –1 s –1 in this exact system. 44 Under these conditions, Fer-1 and Lip-1 were both more reactive than α-TOH ( k inh = (4.7 ± 0.4) × 10 3 M –1 s –1 ), with rate constants of k inh = (4.6 ± 0.8) × 10 4 and (1.2 ± 0.1) × 10 4 M –1 s –1 , respectively.…”