Nucleophilic substitution by amide nitrogen in the aromatic rings of [zn − H]˙+ ions; the structures of the [b2 − H − 17]˙+ and [c1 − 17]+ ions

Abstract

Peptide radical cations that contain an aromatic amino acid residue cleave to give [z_n − H]˙⁺ ions with [b₂ − H − 17]˙⁺ and [c₁ − 17]⁺ ions, the dominant products in the dissociation of [z_n − H]˙⁺, also present in lower abundance in the CID spectra. Isotopic labeling in the aromatic ring of [Y_π˙GG]⁺ establishes that in the formation of [b₂ − H − 17]˙⁺ ions a hydrogen from the δ-position of the Y residue is lost, indicating that nucleophilic substitution on the aromatic ring has occurred. A preliminary DFT investigation of nine plausible structures for the [c₁ − 17]⁺ ion derived from [Y_π˙GG]⁺ shows that two structures resulting from attack on the aromatic ring by oxygen and nitrogen atoms from the peptide backbone have significantly better energies than other isomers. A detailed study of [Y_π˙GG]⁺ using two density functionals, B3LYP and M06-2X, with a 6-31++G(d,p) basis set gives a higher barrier for attack on the aromatic ring of the [z_n − H]˙⁺ ion by nitrogen than by the carbonyl oxygen. However, subsequent rearrangements involving proton transfers are much higher in energy for the oxygen-substituted isomer leading to the conclusion that the [c₁ − 17]⁺ ions are the products of nucleophilic attack by nitrogen, protonated 2,7-dihydroxyquinoline ions. The [b₂ − H − 17]˙⁺ ions are formed by loss of glycine from the same intermediates involved in the formation of the [c₁ − 17]⁺ ions.