Free radicals induced peptide damage in the presence of transition metal ions: A plausible pathway for biological deleterious processes

When aqueons N₂O-saturated solutions containing glycine-N-tert-butylamide (L) and Cr²⁺(aq) or Cu⁺(aq) are irradiated, transients with metal-carbon σ-bonds are formed with rate constants of (4.4 ± 0.5) × 10⁷ and (5.2 ± 0.3) × 10⁹ M^- s^-, respectively. In the chromium(II) system, after a fast process (k = 43 ± 4 s^-1), possibly chelaton, the transient decomposes verly slowly (k = 0.003 ± 0.001 h^-1) via a β-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 σ-bond and the reaction of the transient complex with L-Cu²⁺ compete efficiently with the β-elimination process. The latter reaction leads to some modification of the amide. We suggest that the formation and decomposition od transients with metal-carbon σ-bonds may be describe an additional pathway for peptide damage induced by alipathic free radical precursors (e.g., OH^., H₂O₂) in the presence of transition metal ions.