Oxidation of 4-Methylcatechol:  Implications for the Oxidation of Catecholamines

Abstract

At alkaline pH, 4-methylcatechol oxidizes more rapidly than the related catecholamines: dopamine, norepinephrine, and epinephrine. This oxidation is not inhibited by superoxide dismutase or catalase, indicating that O2 itself is the oxidant, but the reduction potential of O2/O2-* is too low for it to oxidize 4-methylcatechol directly. Instead, O2 oxidizes the 4-methylcatechol semiquinone, which is formed by comproportionation of 4-methylcatechol and its o-quinone. Aniline reacts very quickly with the o-quinone and thus stops the comproportionation reaction that oxidizes 4-methylcatechol to the semiquinone. Oxidation of 4-methylcatechol then requires superoxide, and in the presence of aniline, oxidation of 4-methylcatechol by O2 is inhibited by superoxide dismutase. When catecholamines oxidize, the side chain amine inserts into the catechol o-quinone, forming a bicyclic compound. By eliminating the quinone, this ring closure prevents comproportionation and the consequent oxidation of catecholamines by O2. It also prevents reaction of the quinone with other compounds and the formation of potentially toxic products.

13 reasons why the brain is susceptible to oxidative stress

“…While the initial rate of semiquinone radical formation is often slow [19] , it can be accelerated by redox active transition metals [149] —which are abundant in the brain [17] . Dopamine quinones can combine to yield semiquinones [150] —which react with O 2 to give O 2 .- , with the caveat that this reaction competes with a cyclisation reaction that averts redox cycling [151] . The mix of O 2 .- , H 2 O 2 and .OH detected is indicative of hydroquinone, semi-quinone and quinone equilibria [150] .…”

Elucidation of the interplay between Fe(II), Fe(III), and dopamine with relevance to iron solubilization and reactive oxygen species generation by catecholamines

“…This process, recognized to be pH-dependent as a result of the need for deprotonation of the amino side chain, is a prerequisite to the subsequent cyclization process (Hawley et al 1967). However, the comproportionation between DA and DAC has been considered unlikely to occur presumably because of the effect of the cyclization of the amino side chain in the DAC (Tse et al 1976;Borovansky et al 2006;Li et al 2007). The proposed reaction scheme for DA autoxidation is presented in Fig.…”

Direct Observation of the Interplay of Catechol Binding and Polymer Hydrophobicity in a Mussel-Inspired Elastomeric Adhesive

“…Since catechol is prone to oxidation reactions, it is important to show that the catechol moieties are intact after exposure to the cross-linking conditions. 61 The chemical stabilities of the protected and deprotected elastomers on UV-A exposure were analyzed by UV–vis and ATR/FT-IR absorption spectroscopies after the polymer films were exposed to UV-A irradiation. The UV–vis spectra of elastomers show that the catechol absorption peak (π → π*, λ max = 280 nm) remains intact after cross-linking ( Figure 2 B), indicating the stability of catechol upon UV-A exposure (upon oxidation, red shift is expected).…”