Copper-Mediated Peptide Radical Ions in the Gas Phase

Molecular radical cations, M^•+, of amino acids and oligopeptides are produced by collision-induced dissociation of mixed complex ions, [Cu^II(dien)M]^•2+, that contain Cu^II, an amine, typically diethylenetriamine (dien), and the oligopeptide, M. With dien as the amine ligand, abundant M^•+ formation is observed only for the amino acids tryptophan and tyrosine, and oligopeptides that contain either the tryptophanyl or tyrosyl residue. Dissociation of the M^•+ ion is rich and differs considerably from that of protonated amino acids and peptides. Facile fragmentation occurs around the α-carbon of the tryptophanyl residue. Cleavage of the N−C_α bond and proton transfer from the exocyclic methylene group in the side chain to the N-terminal residue results in formation of the [z_n − H]^•+ ion and elimination of the N-terminal fragment as ammonia or an amide, depending on the position of the tryptophanyl residue. Cleavage of the C_α−C bond of an oligopeptide containing a C-terminal tryptophan residue and proton transfer from the carboxylic group to the N-terminal fragment (a carbonyl oxygen atom) results in formation of the [a_n + H]^•+ ion and elimination of carbon dioxide. Both types of fragmentation have no analogous reactions in protonated peptides. For the M^•+ of tryptophanylglycylglycine, WGG, elimination of the tryptophanyl side chain results in GGG^•+. This radical cation fragments by eliminating its C-terminal glycine to give the [b₂ − H]^•+ ion, which is an oxazolone and shares much of the structure and reactivity of the b₂⁺ ion from protonated triglycine. Density functional theory shows the mechanism of forming the [b₂ − H]^•+ ion is similar to that of the b₂⁺ ion, although the free-energy barrier at 29.4 kcal/mol is lower. The [b₂ − H]^•+ ion eliminates CO readily to give the [a₂ − H]^•+ ion, which is an iminium radical ion.