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.
Goldstein
S
S
Department of Physical Chemistry, Hebrew University of Jerusalem, Israel.
Czapski
G
G
Cohen
H
H
Meyerstein
D
D
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