Side-chain loss reactions of collisionally activated protonated peptoids: A mechanistic insight

Abstract

Peptoids constitute an emergent class of synthetic biocompatible macromolecules that are best described as polymers of N-substituted glycines. Peptides and peptoids are regioisomers with the side chains appended in peptoids to the nitrogen atoms rather than to the α-carbon atoms as in peptides. Peptide sequencing now takes great advantage of collision-induced dissociation experiments, based on the elucidation of the decomposition pathways of protonated peptides. In contrast, data on peptoid ion decompositions are to date scarcely present in the literature. Upon CID, protonated peptoids were recently shown to mostly dissociate by cleavages at the backbone amide bonds yielding B- and Y-fragment ions. In addition, the loss of the side-chain group and/or the formation of the side-chain fragment ion are common reactions for peptoids containing protonated N-α-aromatic side chain.In the present paper, we submitted protonated tailor-made peptoids to (energy-resolved) collision-induced dissociation experiments to investigate the side-chain loss reaction mechanisms. We also used orthogonal methods, such as quantum chemistry, ion mobility spectrometry and infrared photodissociation spectroscopy to establish the structures of the fragment ions. We ended up with different mechanistic scenarios consistent with the nature of the fragment ions and the kinetic energy dependence of decomposition reactions. Our mechanistic proposals associate the proton mobile model, proton bound dimer intermediacy and concerted rearrangement reactions.