Semiquinone Radicals from Oxygenated Polychlorinated Biphenyls: Electron Paramagnetic Resonance Studies

Abstract

Polychlorinated biphenyls (PCBs) can be oxygenated to form very reactive hydroquinone and quinone products. A guiding hypothesis in the PCB research community is that some of the detrimental health effects of some PCBs are a consequence of these oxygenated forms undergoing one-electron oxidation or reduction, generating semiquinone radicals (SQ•−). These radicals can enter into a futile redox cycle resulting in the formation of reactive oxygen species, that is, superoxide and hydrogen peroxide. Here, we examine some of the properties and chemistry of these semiquinone free radicals. Using electron paramagnetic resonance (EPR) to detect SQ•− formation, we observed that (i) xanthine oxidase can reduce quinone PCBs to the corresponding SQ•−; (ii) the heme-containing peroxidases (horseradish and lactoperoxidase) can oxidize hydroquinone PCBs to the corresponding SQ•−; (iii) tyrosinase acting on PCB ortho-hydroquinones leads to the formation of SQ•−; (iv) mixtures of PCB quinone and hydroquinone form SQ•− via a comproportionation reaction; (v) SQ•− are formed when hydroquinone-PCBs undergo autoxidation in high pH buffer (≈>pH 8); and, surprisingly, (vi) quinone-PCBs in high pH buffer can also form SQ•−; (vii) these observations along with EPR suggest that hydroxide anion can add to the quinone ring; (viii) H2O2 in basic solution reacts rapidly with PCB-quinones; and (ix) at near-neutral pH SOD can catalyze the oxidization of PCB-hydroquinone to quinone, yielding H2O2. However, using 5,5-dimethylpyrroline-1-oxide (DMPO) as a spin-trapping agent, we did not trap superoxide, indicating that generation of superoxide from SQ•− is not kinetically favorable. These observations demonstrate multiple routes for the formation of SQ•− from PCB-quinones and hydroquinones. Our data also point to futile redox cycling as being one mechanism by which oxygenated PCBs can lead to the formation of reactive oxygen species, but this is most efficient in the presence of SOD.

Oxidation of 3,4-Dihydroxyphenylacetaldehyde, a Toxic Dopaminergic Metabolite, to a Semiquinone Radical and an ortho-Quinone

“…However, the max of the initial species was higher than expected for a quinone (35). Its transient nature and the susceptibility of quinones to undergo comproportionation (30) in the presence of their reduced counterparts (i.e. hydroquinones and catechols) suggested that the pink species was a radical (Scheme 2).…”

“…DOPAL Auto-oxidation and ROS Production-Superoxide formation during DOPAL auto-oxidation was investigated using the method of Eyer (30,33). UV-visible spectrophotometry (kinetic settings) was used to measure the change in absorbance at 400 nm during auto-oxidation of DOPAL (0.5 mM) in 50 mM NaH 2 PO 4 , pH 7.8.…”

“…6B). Equilibrium for this reaction generally favors reactants (30). However, the presence of SOD can shift the equilibrium toward the products by rapid dismutation of superoxide, effectively "pulling" the reaction.…”

MnSOD activity regulates hydroxytyrosol-induced extension of chronological lifespan

“…6b). HT-quinone may interact with HT in a comproportionation reaction to generate more semiquinone radicals (Song and Buettner 2010;Song et al 2008;Song et al 2009). This redox cycle of HT could elicit an oxidative stress response and cells may adapt to this oxidative insult by promoting their antioxidant defense system.…”

“…6a). Semiquinone radicals are the primary source for formation of superoxide from the hydroquinonesemiquinone-quinone triad (Eyer 1991;Song and Buettner 2010;Song et al 2008;Venkatesha et al 2008). If superoxide is formed in the oxidation of hydroquinones that have relatively high redox potentials, then superoxide dismutase will accelerate the oxidation of hydroquinone, forming quinone.…”