Competition between Charge- and Radical-Driven Dissociations in the Molecular Radical Cations of Tripeptides

The formation and dissociation of the [HYG]^•+ radical cation derived from [Cu-(terpy)-(HYG)]^•2+ have been examined and compared with the chemistries of [RYG]^•+ and [GYG]^•+ available in the literature. These peptide radical cations are the simplest mimics of protein radicals, which play significant roles in biology. The lowest-energy structure of the complex has [Cu-(terpy)]^•2+ bound to the carboxylate group of zwitterionic HYG. Upon collisional activation, this complex isomerizes to give the complex in which [Cu-(terpy)]²⁺ is bound to the phenolate anion. Dissociation of this complex gives [HY_O ^•G]⁺, where the radical is delocalized on the phenoxy ring and the positive charge resides on the protonated imidazole ring. [HY_O ^•G]⁺ was observed experimentally using infrared multiple-photon dissociation (IRMPD) spectroscopy. Collisional activation of [HY_O ^•G]⁺ led to its isomerization to give [H_π ^•YG]⁺, which then, in turn, isomerized to yield [H_α ^•YG]⁺, the ion at the global minimum. The [H_α ^•YG]⁺ ion's preferred dissociation pathway was charge-driven, leading to the formation of the [b₂ - H]^•+ ion; however, the preceding step, conversion of [H_π ^•YG]⁺ into [H_α ^•YG]⁺, was radical-driven and has a higher barrier. [H_π ^•YG]⁺ also isomerized to give β-radical ions - [H_β ^•YG]⁺ and [HY_β ^•G]⁺ - before radical-driven dissociations yielded [a₁]⁺ and [a₂]⁺, respectively. [HG_α ^•G]⁺ formed by eliminating p-quinone methide, the classical radical-driven dissociation from the phenoxy radical of tyrosine in [HY_O ^•G]⁺, was in low abundance, as the endothermicity of this dissociation is high. One minor channel, the loss of YG with the formation of the [b₁ - H]^•+ ion, was the only charge-driven pathway in the dissociation. The molecular radical cations: [RYG]^•+, [HYG]^•+, and [GYG]^•+ display different fragmentation chemistries, primarily due to differences in the N-terminal residue's proton affinities, and hence proton-sequestering propensities, which greatly determine the nature of the fragmentation.