141272-05-1Relevant articles and documents
Chemical and enzyme-mediated oxidation of the serotonergic neurotoxin 5,7- dihydroxytryptamine: Mechanistic insights
Tabatabaie,Dryhurst
, p. 2261 - 2274 (1992)
The oxidation chemistry and biochemistry of the serotonergic neurotoxin 5,7-dihydroxytryptamine (1) has been studied under anaerobic and aerobic conditions in aqueous solution at physiological pH. Under anaerobic conditions, one-electron oxidants (ferricytochrome c, peroxidase/H2O2, ceruloplasmin, Cu2+) generate a radical intermediate. Dimerization of the C(6)-centered resonance form of this radical followed by secondary oxidations yields 3-(2-aminoethyl)-6-[3-(2-aminoethyl)-1,7-dihydro-5-hydroxy-7-oxo-6H- indol-6-ylidene]-1-H-indole-5,7(4H,6H)-dione. Under aerobic conditions, molecular O2 attacks the C(4)-centered 1 radical to yield a hydroperoxy radical which decomposes to 5-hydroxytryptamine-4,7-dione (2). Autoxidation of 1 proceeds by primary attack by molecular O2 on a C(4)-centered carbanion to form a superoxide-radical complex. This rearranges to a C(4)-centered hydroperoxide which decomposes to 2. A C(6)-centered carbanion of 1 combines with 2 to give, ultimately, 6,6'-bi-5-hydroxytryptamine-4,7-dione (3). Trace concentrations of transition metal ions (Fe3+, Fe2+, Cu2+, Mn2+) catalyze the autoxidation of 1 by catalytic cycles in which a hydroperoxide intermediate plays key roles. A byproduct of the transition metal-catalyzed oxidation of 1 is superoxide, O2·-. Because of its enormous basicity O2·- facilitates deprotonation of 1. The C(4)-centered carbanion so produced is oxidized by molecular O2 or by the hydroperoxy radical (HO2·) to give radical intermediates and thence 2 and 3. Mechanistic pathways leading to the various products of oxidation of 1 are proposed and the potential roles of oxidation reactions of the indolamine are related to its neurodegenerative properties.
