Mechanistic investigation of phosphate ester bond cleavages of glycylphosphoserinyltryptophan radical cations under low-energy collision-induced dissociation

摘要

Under the conditions of low-energy collision-induced dissociation (CID), the canonical glycylphosphoserinyltryptophan radical cation having its radical located on the side chain of the tryptophan residue ([G _p SW] ~(?+)) fragments differently from its tautomer with the radical initially generated on the α-carbon atom of the glycine residue ([G ? _p SW]~+). The dissociation of [G ? _p SW]+ is dominated by the neutral loss of H_3PO_4 (98 Da), with backbone cleavage forming the [b_2 - H]~(?+)/y_1 ~+ pair as the minor products. In contrast, for [G _p SW]~(?+), competitive cleavages along the peptide backbone, such as the formation of [G _p SW - CO_2]~(?+) and the [c_2 + 2H]+/[z_1 - H]~(?+) pair, significantly suppress the loss of neutral H_3PO_4. In this study, we used density functional theory (DFT) to examine the mechanisms for the tautomerizations of [G? _p SW]+ and [G p SW]~(?+) and their dissociation pathways. Our results suggest that the dissociation reactions of these two peptide radical cations are more efficient than their tautomerizations, as supported by Rice-Ramsperger-Kassel-Marcus (RRKM) modeling. We also propose that the loss of H_3PO_4 from both of these two radical cationic tautomers is preferentially charge-driven, similar to the analogous dissociations of even-electron protonated peptides. The distonic radical cationic character of [G? _p SW]~+ results in its charge being more mobile, thereby favoring charge-driven loss of H_3PO_4; in contrast, radical-driven pathways are more competitive during the CID of [G _p SW]~(?+). [Figure not available: see fulltext.]