Discovery and Mechanistic Studies of Facile N‑Terminal Cα–C Bond Cleavages in the Dissociation of Tyrosine-Containing Peptide Radical Cations

Fascinating N-terminal Cα–C bond cleavages in a series of nonbasic tyrosine-containing peptide radical cations have been observed under low-energy collision-induced dissociation (CID), leading to the generation of rarely observed x-type radical fragments, with significant abundances. CID experiments of the radical cations of the alanyltyrosylglycine tripeptide and its analogues suggested that the N-terminal Cα–C bond cleavage, yielding its [x2 + H]•+ radical cation, does not involve an N-terminal α-carbon-centered radical. Theoretical examination of a prototypical radical cation of the alanyltyrosine dipeptide, using density functional theory calculations, suggested that direct N-terminal Cα–C bond cleavage could produce an ion–molecule complex formed between the incipient a1 + and x1 • fragments. Subsequent proton transfer from the iminium nitrogen atom in a1 + to the acyl carbon atom in x1 • results in the observable [x1 + H]•+. The barriers against this novel Cα–C bond cleavage and the competitive N–Cα bond cleavage, forming the complementary [c1 + 2H]+/[z1 – H]•+ ion pair, are similar (ca. 16 kcal mol–1). Rice–Ramsperger–Kassel–Marcus modeling revealed that [x1 + H]•+ and [c1 + 2H]+ species are formed with comparable rates, in agreement with energy-resolved CID experiments for [AY]•+.