Molecular Pharmacology, Vol 18, 594-597, Copyright © 1980 by the American Society for Pharmacology and Experimental Therapeutics

Electron Spin Resonance Study of the Autoxidation of 6-Aminodopamine

¹ Laboratory of Environmental Biophysics, National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, North Carolina 27709

Although the mechanism of neurotoxicity of 6-aminodopamine and 6-hydroxydopamine is generally agreed to be initiated by the nonenzymatic oxidation of these compounds by molecular oxygen, most studies have focused on subsequent chemical and biological events. This ESR study indicates that this initial reaction can be described as a one-electron transfer from the neurotoxins to molecular oxygen to form their respective semiquinone (or semiquinone-imine) free radicals. Using a combination of deuterium isotope substitution and a resolution enhancement technique, a nearly complete assignment of the hyperfine splitting constants of the ESR spectrum of the 6-aminodopamine has been made. A relatively large interaction of the unpaired electron with the nitrogen of the amino group attached to the phenyl ring emphasizes the semiquinone-imine character of this free radical. The analysis of the ESR spectrum excludes any possibility that this free radical is a secondary product of autoxidation such as the 5,6-dihydroxyindole semiquinone-imine free radical.

Note:
ACKNOWLEDGMENTS We would like to express our thanks to R. B. Clarkson, C. A. Evans, and D. S. Leniart of Varian Associates as well as J.S. Hyde and H. Van Willigen for enlightening discussions concerning this resolution enhancement technique, which we only belatedly discovered.