CHEMISTRY OF C-2 GLYCERYL RADICALS - INDICATIONS FOR A NEW MECHANISM OF LIPID DAMAGE

Precursors for the selective generation of C-2 glyceryl radicals were synthesized, and the chemical behavior of the corresponding radicals w as investigated by ESR spectroscopy, product analysis, and kinetic mea surements. It was found that cleavage of the beta-C,O bond proceeds ra pidly, if a hydroxyl group is present at the radical carbon center. Th e rate constant for the elimination of a beta-acetoxy group from radic al 30 was dependent on the solvent (k(E)=4x10(5) s(-1) in methanol, k( E)=2x10(7) s(-1) in toluene). With these results and ab initio calcula tions a concerted elimination mechanism is suggested. alpha-Methoxy-su bstituted C-2 glyceryl radicals 42 and 43 showed heterolytic beta-C,O bond cleavage under formation of radical cations. With ester-substitut ed radicals 24 and 35 no elimination could be observed. To demonstrate the biological significance of these findings, C-2 lysolecithin radic al 53 was generated, which led to fast beta-elimination.