Discovery and mechanistic studies of facile N-terminal C α-C bond cleavages in the dissociation of tyrosine-containing peptide radical cations

Fascinating N-terminal C_α-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 C_α-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 C _α-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 x ₁^• results in the observable [x₁ + H] ^•+. The barriers against this novel C_α-C bond cleavage and the competitive N-C_α 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]^•+. © 2014 American Chemical Society.