Electron predators are hydrogen atom traps. Effects of aryl groups on N-C(α) bond dissociations of peptide radicals.

Effects of substituted aryl groups on dissociations of peptide aminoketyl radicals were studied computationally for model tetrapeptide intermediates GXD(•) G where X was a cysteine residue that was derivatized by S-(3-nitrobenzyl), S-(3-cyanobenzyl), S-(3,5-dicyanobenzyl), S-(2,3,4,5,6-pentafluorobenzyl), and S-benzyl groups. The aminoketyl radical was placed within the Asp amide group. Aminoketyl radicals having the S-(3-nitrobenzyl) group were found to undergo spontaneous and highly exothermic migration of the hydroxyl hydrogen atom onto the nitro group in conformers allowing interaction between these groups. Competing reaction channels were investigated for aminoketyl radicals having the S-(3-cyanobenzyl) and S-(3,5-dicyanobenzyl) groups, e.g. H-atom migration to the C and N atoms of the C≡N group, migration to the C-4 position of the phenyl ring, and dissociation of the radical-activated NC(α) bond between the Asp and Gly residues. RRKM kinetic analysis on the combined B3LYP and ROMP2/6-311++G(2d,p) potential energy surface indicated > 99% H-atom transfer to the C≡N group forming a stable iminyl intermediate. The NC(α) bond dissociation was negligible. In contrast, peptides with the S-(2,3,4,5,6-pentafluorobenzyl) and S-benzyl groups showed preferential NC(α) bond dissociation that outcompeted H-atom migration to the C-4 position and fluorine substituents in the phenyl ring. These computational results are used to suggest an alternative mechanism for the quenching effect on electron-based peptide backbone dissociations of benzyl groups with electron-withdrawing substitutents, as reported recently.