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 [DGαR]+ 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 [DGαR]+ are approximately 30 and 36 kcal mol−1, respectively.