Thermodynamic and kinetic considerations for the reaction of semiquinone radicals to form superoxide and hydrogen peroxide

Abstract

The quinone/semiquinone/hydroquinone triad (Q/SQ •− /H 2 Q) represents a class of compounds that has great importance in a wide range of biological processes. The half-cell reduction potentials of these redox couples in aqueous solutions at neutral pH, E°′, provide a window to understanding the thermodynamic and kinetic characteristics of this triad and their associated chemistry and biochemistry in vivo. Substituents on the quinone ring can significantly influence the electron density "on the ring" and thus modify E°′ dramatically. E°′ of the quinone governs the reaction of semiquinone with dioxygen to form superoxide. At near-neutral pH the pK a 's of the hydroquinone are outstanding indicators of the electron density in the aromatic ring of the members of these triads (electrophilicity) and thus are excellent tools to predict half-cell reduction potentials for both the one-electron and two-electron couples, which in turn allow estimates of rate constants for the reactions of these triads. For example, the higher the pK a 's of H 2 Q, the lower the reduction potentials and the higher the rate constants for the reaction of SQ •− with dioxygen to form superoxide. However, hydroquinone autoxidation is controlled by the concentration of di-ionized hydroquinone; thus, the lower the pK a 's the less stable H 2 Q to autoxidation. Catalysts, e.g., metals and quinone, can accelerate oxidation processes; by removing superoxide and increasing the rate of formation of quinone, superoxide dismutase can accelerate oxidation of hydroquinones and thereby increase the flux of hydrogen peroxide. The principal reactions of quinones are with nucleophiles via Michael addition, for example, with thiols and amines. The rate constants for these addition reactions are also related to E°′. Thus, pK a 's of a hydroquinone and E°′ are central to the chemistry of these triads.

The Electrochemical Reaction Mechanism and Applications of Quinones

“…24,25 It is found that the pK a values of hydroquinone are much bigger than that of the semiquinone while E Q/Q•− and E Q•−/Q2− are similar; normally the pK a of QH…”

“…It is deemed that the primary mechanism of highly toxic superoxide generation via quinone compounds involves the semiquinone radical. 25,46 Autoxidation of hydroquinones by O 2 is known to be catalyzed by Q ox , because Q ox can produce Q sem by reacting with hydroquinone, Q red . In the Q cycle of mitochondria, it is very difficult to observe the semiquinone radical at the Q o site, which probably acts to suppress superoxide generation.…”

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.…”

The ToxBank Data Warehouse: Supporting the Replacement of In Vivo Repeated Dose Systemic Toxicity Testing

“…Reoxidation of these agents requires strong oxidizing systems such as the cytochrome P450's so that toxicity is limited to metabolizing organs such as liver and kidney. [55,63,64] …”