Radical-induced dissociation leading to the loss of CO2 from the oxazolone ring of [b5 − H]˙+ ions

Abstract

Macrocyclization is commonly observed in large b_n⁺ (n ≥ 4) ions and as a consequence can lead to incorrect protein identification due to sequence scrambling. In this work, the analogous [b₅ − H]˙⁺ radical cations derived from aliphatic hexapeptides (GA₅˙⁺) also showed evidence of macrocyclization under CID conditions. However, the major fragmentation for [b₅ − H]˙⁺ ions is the loss of CO₂ and not CO loss, which is commonly observed in closed-shell b_n⁺ ions. Isotopic labeling using CD₃ and ¹⁸O revealed that more than one common structure underwent dissociations. Theoretical studies found that the loss of CO₂ is radical-driven and is facilitated by the radical being located at the C_α atom immediately adjacent to the oxazolone ring. Comparable energy barriers against macrocyclization, hydrogen-atom transfer, and fragmentations are found by DFT calculations and the results are consistent with the experimental observations that a variety of dissociation products are observed in the CID spectra.