Structure and Fragmentation Chemistry of the Peptide Radical Cations of Glycylphenylalanylglycine (GFG)

Abstract

<p>Herein, we explore the generation and characterization of the radical cations of glycylphenylalanylglycine, or [GFG]^•+, formed via dissociative electron-transfer reaction from the tripeptide to copper(II) within a ternary complex. A comprehensive investigation employing isotopic labeling, infrared multiple-photon dissociation (IRMPD) spectroscopy , and density functional theory (DFT) calculations elucidated the details and energetics in formation of the peptide radical cations as well as their dissociation products. Unlike conventional aromatic-containing peptide radical cations that primarily form canonical π-radicals, our findings reveal that 75% of the population of the experimentally produced [GFG]^•+precursors are [GF_α^•G]⁺, where the radical resides on the middle α-carbon of the phenylalanyl residue. This unexpected isomeric ion has an enthalpy of 6.8 kcal/mol above the global minimum, which has an N-terminal captodative structure, [G_α^•FG]⁺, comprising 25% of the population. The [b₂-H]^•+ product ions are also present in a ratio of 75/25 from [GF_α^•G]⁺/ [G_α^•FG]⁺, the results of which are obtained from matches between the IRMPD action spectrum and predicted IR absorption spectra of the [b₂-H]^•+ candidate structures, as well as from IRMPD isomer population analyses.</p>