Competitive hydrogen atom migrations accompanying cascade dissociations of peptide cation-radicals of the + type

Abstract

We report a combined experimental and computational study of energy-resolved collision-induced dissociation (ER-CID) and time-resolved infrared multiphoton dissociation (TR-IRMPD) of z4 ions prepared by electron transfer dissociation of peptide (Ala-Ala-Asn-Ala-Arg + 2H)2+ ions. The z4 cation-radicals, •ANAR+, undergo competitive dissociations by backbone cleavage and loss of a CONH2 radical from the Asn side chain. The backbone cleavage proceeds by radical-assisted dissociation of the Asn Cα—CO bond, forming an x2 ion intermediate which rapidly dissociates by HNCO elimination to yield a stable z2 fragment ion, •AR+. The ER-CID and TR-IRMPD data were consistent with the consecutive nature of the backbone dissociation but showed different branching ratios for the two major fragmentations. The ER-CID data showed branching ratios 0.6-1.0 for the side-chain and backbone cleavages whereas the TR-IRMPD data showed an earlier onset for the latter dissociation. Computational analysis of the potential energy surface with density functional theory and ab initio calculations was carried out to provide structures and energies for the reactant ions as well as several intermediates, products, and transition states. Dissociation pathways for cis and trans amide conformers were distinguished and their energies were evaluated. The threshold dissociation energies for the backbone and side-chain dissociations were similar in accordance with the experimental ER-CID branching ratio. The TR-IRMPD data were interpreted by different absorbances of intermediates produced by hydrogen atom migrations along the dissociation pathways.

Near-UV photodissociation of phosphopeptide cation-radicals

“…The transition state energy for the Ala-2-H  migration (TS1, 109 kJ mol -1 , Table 1) was very similar to TS energies for analogous H  migrations reported previously for • ANAR + , • ASAR + , and • ATAR + peptide z ions (100-123 kJ mol -1 ) [48,69], indicating that these reactions share common features regarding electronic and steric factors affecting the TS energy. The subsequent CO-NH bond dissociation in the cis-Ala-2--radical 3 can proceed through TS2 at 138 kJ mol -1 relative to 1.…”

The Role of Electron Transfer Dissociation in Modern Proteomics

“… 293 Additionally, Turacek and colleagues have used radical product ions, created via ETD, to extensively study structure and ion chemistry of peptides with a variety of approaches for theoretical and analytical purposes. 294 − 300 …”

Tautomerization and Dissociation of Molecular Peptide Radical Cations

“…The N–C α bond cleavages can also lead to the generation of [z n −1 + H] •+ species via either the peptide radical cation directly or the fragment ion [x n −1 + H] •+ , involving a β‐radical–driven N–C α bond‐cleavage process . The c/z‐type ions can also be produced from hydrogen‐rich peptide radical cations [M + n H] •( n −1)+ generated using ECD or ETD . Theoretical investigations have suggested that an aminoketyl radical intermediate would form and undergo a homolytic cleavage of the adjacent N–C α bond to give an ion–molecule complex .…”