Journal of Medicinal Chemistry 1988-02-01

Synthesis of spin traps specific for hydroxyl radical.

G M Rosen, M J Turner

Index: J. Med. Chem. 31(2) , 428-32, (1988)

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Abstract

Two nitrones, 3,3-diethyl-5,5-dimethylpyrroline 1-oxide (DEDMPO) and 3,3,5,5-tetramethylpyrroline 1-oxide (M4PO), were synthesized by the zinc/ammonium chloride reduction of appropiately substituted gamma-nitrocarbonyl compounds, followed by addition of methylmagnesium bromide to the resulting intermediate nitrones. The lipophilicities of these nitrones were estimated by determining their partition coefficients in an 1-octanol/water system. They were found to be considerably more lipophilic than 5,5-dimethylpyrroline 1-oxide (DMPO). The spin trapping of hydroxyl and superoxide radicals with these nitrones was investigated, and the hyperfine coupling constants were determined. M4PO was found to spin trap both free radicals, while DEDMPO spin trapped only hydroxyl radical. DEDMPO was used to determine if hydroxyl radical was produced during the metabolism of menadione or nitrazepam by porcine thoracic aorta endothelial cells. Our results indicate, in conjunction with spin-trapping studies utilizing DMPO, that only superoxide is generated during cellular metabolism of quinones and aromatic nitro-containing compounds by endothelial cells.