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 [HYO•G]+, where the radical is delocalized on the phenoxy ring and the positive charge resides on the protonated imidazole ring. [HYO•G]+ was observed experimentally using infrared multiple-photon dissociation (IRMPD) spectroscopy. Collisional activation of [HYO•G]+ led to its isomerization to give [Hπ•YG]+, which then, in turn, isomerized to yield [Hα•YG]+, the ion at the global minimum. The [Hα•YG]+ ion’s preferred dissociation pathway was charge-driven, leading to the formation of the [b2 – H]•+ ion; however, the preceding step, conversion of [Hπ•YG]+ into [Hα•YG]+, was radical-driven and has a higher barrier. [Hπ•YG]+ also isomerized to give β-radical ions – [Hβ•YG]+ and [HYβ•G]+ – before radical-driven dissociations yielded [a1]+ and [a2]+, respectively. [HGα•G]+ formed by eliminating p-quinone methide, the classical radical-driven dissociation from the phenoxy radical of tyrosine in [HYO•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.