GENERATION OF 5,5-DIMETHYL-1-PYRROLINE N-OXIDE HYDROXYL AND SCAVENGERRADICAL ADDUCTS FROM COPPER H2O2 MIXTURES - EFFECTS OF METAL-ION CHELATION AND THE SEARCH FOR HIGH-VALENT METAL-OXYGEN INTERMEDIATES/

Citation
Mj. Burkitt et al., GENERATION OF 5,5-DIMETHYL-1-PYRROLINE N-OXIDE HYDROXYL AND SCAVENGERRADICAL ADDUCTS FROM COPPER H2O2 MIXTURES - EFFECTS OF METAL-ION CHELATION AND THE SEARCH FOR HIGH-VALENT METAL-OXYGEN INTERMEDIATES/, Archives of biochemistry and biophysics, 323(1), 1995, pp. 63-70
Citations number
29
Categorie Soggetti
Biology,Biophysics
ISSN journal
00039861
Volume
323
Issue
1
Year of publication
1995
Pages
63 - 70
Database
ISI
SICI code
0003-9861(1995)323:1<63:GO5NHA>2.0.ZU;2-Q
Abstract
A metal-catalyzed nucleophilic addition mechanism for the formation of radical adducts of the spin trap 5,5-dimethyl-1-pyrroline N-oxide (DM PO) has been described recently (It. Makino, T. Hagiwara, A Hagi, M. N ishi, and A Murakami, 1990, Biochem. Biophys. Res. Commun. 172, 1073-1 080; P. M. Hanna, W. Chamulitrat, and R. P. Mason, 1992, Arch. Biochem . Biophys. 296, 640-644). In the present investigation, we have demons trated that the recently reported inhibition of copper-dependent hydro xyl radical formation by the complexing agent 1,10-phenanthroline (OP) , which appears to contradict the well-known chemical nuclease propert ies of Cu-I(OP)(2), is an artifact resulting from an inhibition of the nucleophilic addition of water to DMPO by OP (A C. Mello-Filho and R. Meneghini, 1991, Mutat. Res. 251, 109-113). Copper bound to OP was fo und to be a good catalyst of hydroxyl radical formation: the Cu-II(OP) (2) complex can be reduced by H2O2 and the Cu-(I)(OP)(2) generated rea cts with the peroxide to form (OH)-O-.. In contrast, no evidence could be obtained for oxidant formation from the Cu-(aq(II))/H2O2 reaction system, despite the detection of a prominent signal from the DMPO hydr oxyl radical adduct (DMPO/(OH)-O-.) (the formation of which was due so lely to the nucleophilic addition of water to DMPO). The failure to ge nerate an oxidant in this reaction mixture was attributed to the failu re of hydrogen peroxide to reduce Cu-(aq(II)), as hydroxyl radical for mation did occur when Cu-(aq(I)) was added directly to H2O2. However, in order to account for the high concentration of alpha-hydroxyethanol radicals detected when ethanol was included in the Cu-(aq(I))/H2O2 re action, the possibility that an oxidant in addition to (OH)-O-. (e.g., CuO+) is generated is discussed. (C) 1995 Academic Press, Inc.