Mechanistic examination of Cβ-Cγ bond cleavages of tryptophan residues during dissociations of molecular peptide radical cations

In this study, we used collision-induced dissociation (CID) to examine the gas-phase fragmentations of [G_nW]^•+ (n = 2-4) and [GXW]^•+ (X = C, S, L, F, Y, Q) species. The C _β-C_γ bond cleavage of a C-terminal decarboxylated tryptophan residue ([M - CO₂]^•+) can generate [M - CO₂ - 116]⁺, [M - CO₂ - 117] ^•+, and [1H-indole]^•+ (m/z 117) species as possible product ions. Competition between the formation of [M - CO₂ - 116]⁺ and [1H-indole]^•+ systems implies the existence of a proton-bound dimer formed between the indole ring and peptide backbone. Formation of such a proton-bound dimer is facile via a protonation of the tryptophan γ-carbon atom as suggested by density functional theory (DFT) calculations. DFT calculations also suggested the initially formed ion 2, the decarboxylated species that is active against C_β-C _γ bond cleavage, can efficiently isomerize to form a more stable π-radical isomer (ion 9) as supported by Rice-Ramsperger-Kassel-Marcus (RRKM) modeling. The C_β-C_γ bond cleavage of a tryptophan residue also can occur directly from peptide radical cations containing a basic residue. CID of [WG_nR]^•+ (n = 1-3) radical cations consistently resulted in predominant formation of [M - 116]⁺ product ions. It appears that the basic arginine residue tightly sequesters the proton and allows the charge-remote C_β- C_γ bond cleavage to prevail over the charge-directed one. DFT calculations predicted that the barrier for the former is 6.2 kcal mol ^-1 lower than that of the latter. Furthermore, the pathway involving a salt-bridge intermediate also was accessible during such a bond cleavage event. © 2012 American Chemical Society.