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.