Electron paramagnetic spin trapping studies of the system containing the copper(II) complex of the neurotoxin β-ODAP (3-N-Oxalyl-L-2,3-diaminopropanoic acid) and hydrogen peroxide

Abstract

Electron paramagnetic spin trapping was used to measure the ability of a system containing the copper(II) complex of the excitatory neurotoxic compound β-ODAP (3-N-oxalyl-L-2,3-diaminopropanoic acid) and hydrogen peroxide to form the hydroxyl radical spin adduct of the spin trapping agent DMPO (5,5-dimethyl-1-pyrroline-N-oxide). The hydroxylation of DMPO occurred without the formation of free hydroxyl radical. Hydroxylation of DMPO may be occurring through a high-valence copper intermediate or a bound copper-peroxo intermediate. The neurotoxicity of β-ODAP may be related to its ability to form a strong complex with copper(II) and to react with hydrogen peroxide to form a strongly oxidizing species with hydroxyl radical-like reactivity that is capable of damaging biological components. Molecular modeling of the copper(II)-β-ODAP complex was also carried out in order to identify possible structures of the complex.