α-Radical-induced CO₂ loss from the aspartic acid side chain of the collisionally induced tripeptide aspartylglycylarginine radical cation

Predominant loss of neutral CO₂ has been observed under conditions of low-energy collision-induced dissociation from a prototypical molecular radical cation of the tripeptide aspartylglycylarginine ([DGR]^•+). The decarboxylation occurs mainly from the side chain of the aspartic acid residue and partially from the C-terminal carboxyl group. The structural and mechanistic features that facilitate CO₂ loss from the Asp side chain of [DGR]^•+ and its chemically modified analogs incorporating methylation have been elucidated using a combination of Rice-Ramsperger-Kassel-Marcus modeling and density functional theory at the B3LYP/6-31++G(d,p) level. Current mechanistic investigations suggest that the loss of CO₂ from the side chain of the aspartic acid residue involves hydrogen atom transfer from its carboxyl oxygen atom in conjunction with α-centered radical transfer to the β-centered radical on the aspartic acid side chain. Minor CO₂ loss from the C-terminal carboxyl group occurs through the [DG_α^•R]⁺ isomer, with the radical migrating to the α-carbon of the middle Gly residue. Barriers against the CO₂ loss from the side chain of the aspartic acid residue and from the C-terminus of [DG_α^•R]⁺ are approximately 30 and 36 kcal mol^-1, respectively.