FREE-RADICALS INDUCED PEPTIDE DAMAGE IN THE PRESENCE OF TRANSITION-METAL IONS - A PLAUSIBLE PATHWAY FOR BIOLOGICAL DELETERIOUS PROCESSES

When aqueous N2O-saturated solutions containing glycine-N-tert-butylamide (L) and Cr2+(aq) or Cu+(aq) are irradiated, transients with metal-carbon a-bonds are formed with rate constants of(4.4 +/- 0.5) X 10(7) and (5.2 +/- 0.3) x 10(9) M(-1) s(-1), respectively. In the chromium(II) system, after a fast process (k = 43 +/- 4 s(-1)), possibly chelation, the transient decomposes very slowly (k = 0.003 +/- 0.001 h(-1)) via a beta-elimination process to yield 2-methylpropene and glycinamide, i.e., a cleavage of the peptide bond takes place. However, in the copper(I) system the heterolytic cleavage of the a-bond and the reaction of the transient complex with L-Cu2+ compete efficiently with the B-elimination process. The latter reaction leads to some modification of the amide. We suggest that the formation and decomposition of transients with metal-carbon a-bonds may describe an additional pathway for peptide damage induced by aliphatic free radical precursors (e.g., OH., H2O2) in the presence of transition metal ions.