Chemistry of C-2 glyceryl radicals: Indications for a new mechanism of lipid damage

Article abstract of DOI:10.1021/ja9641416

Precursors for the selective generation of C-2 glyceryl radicals were synthesized, and the chemical behavior of the corresponding radicals was investigated by ESR spectroscopy, product analysis, and kinetic measurements. It was found that cleavage of the β-C,O bond proceeds rapidly, if a hydroxyl group is present at the radical carbon center. The rate constant for the elimination of a β-acetoxy group from radical 30 was dependent on the solvent (k(E) = 4 x 10⁵ s^-1 in methanol, k(E) = 2 x 10⁷ s^-1 in toluene). With these results and ab initio calculations a concerted elimination mechanism is suggested. α-Methoxy-substituted C-2 glyceryl radicals 42 and 43 showed heterolytic β-C,O bond cleavage under formation of radical cations. With ester-substituted radicals 24 and 35 no elimination could be observed. To demonstrate the biological significance of these findings, C-2 lysolecithin radical 53 was generated, which led to fast β-elimination.