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 sigma-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 sigma-bond and the reaction of the transient complex with L-Cu2+ compete efficiently with the beta-elimination process. The latter reaction leads to some modification of the amide. We suggest that the formation and decomposition of transients with metal-carbon sigma-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.
Department of Physical Chemistry, Hebrew University of Jerusalem, Israel.
S
S
Goldstein
G
G
Czapski
H
H
Cohen
D
D
Meyerstein
D002857:Chromium / Q000633:toxicity; D003300:Copper / Q000633:toxicity; D005609:Free Radicals; D005998:Glycine / Q000031:analogs & derivatives; D007202:Indicators and Reagents; D007700:Kinetics; D010315:Particle Accelerators; D010455:Peptides / Q000737:chemistry*
D005609:Free Radicals; D007202:Indicators and Reagents; D010455:Peptides; C090174:glycine-N-tert-butylamide; D002857:Chromium; D003300:Copper; D005998:Glycine