Tautomerization and Dissociation of Molecular Peptide Radical Cations

Abstract

Radical-mediated dissociations of peptide radical cations have intriguing unimolecular gas phase chemistry, with cleavages of almost every bond of the peptide backbone and amino acid side chains in a competitive and apparently "stochastic" manner. Challenges of unraveling mechanistic details are related to complex tautomerizations prior to dissociations. Recent conjunctions of experimental and theoretical investigations have revealed the existence of non-interconvertible isobaric tautomers with a variety of radical-site-specific initial structures, generated from dissociative electron transfer of ternary metal-ligand-peptide complexes. Their reactivity is influenced by the tautomerization barriers, perturbing the nature, location, or number of radical and charge site(s), which also determine the energetics and dynamics of the subsequent radical-mediated dissociatons. The competitive radical- and charge-induced dissociations are extremely dependent on charge density. Charge sequesting can reduce the charge densities on the peptide backbone and hence enhance the flexibility of structural rearrangement. Analysing the structures of precursors, intermediates and products has led to the discovery of many novel radical migration prior to peptide backbone and/or side chain fragmentations. Upon these successes, scientists will be able to build peptide cationic analogues/tautomers having a variety of well-defined radical sites.

Investigation of the position of the radical in z3-ions resulting from electron transfer dissociation using infrared ion spectroscopy

“…[62][63][64] The location of the unpaired electron in the ExD-generated z-type radical cation is assumed to be a major factor determining the cleavages of the backbone or the side chains of the peptide. 65 For example, CID has been applied on a systematically varied set of z-ions resulting from the ETD of the Scheme 1 Schematic representation of the formation of z-type product ions formed by electron transfer dissociation and possible radical migration within the product ion. The radical can possibly migrate from the cleavage site (C a -position) to the C b -or C g -positions of the same residue.…”

Formation of n → π+ interaction facilitating dissociative electron transfer in isolated tyrosine-containing molecular peptide radical cations

“…One possibility is to form a g-radical precursor of M + in which a hydrogen atom of the g-carbon in the side chain of the corresponding residue was replaced by an unpaired electron. [47][48][49][50] However, there are no such g-hydrogen atoms in the side chain of Phe. Even they do, like for the cases of Val and Ile, the g-radical would trigger elimination of an alkene rather than a radical from their side chains.…”

Generation, Characterization, and Dissociation of Radical Cations Derived from Prolyl-glycyl-glycine

“…Peptide radical cations can be divided into two classes, both of which have been examined extensively using mass spectrometry (MS) . Hydrogen-rich ions, [M + 2H] •+ , frequently formed by the capture of an electron by doubly protonated peptides, characteristically dissociate by the cleavage of a bond between an amide nitrogen and the α-carbon of the same amino acid residue, thereby creating z- and c-type ions. − Hydrogen-deficient peptide radical cations (M •+ ), formed by oxidation of a peptide, often by reduction of a metal ion in a peptide complex, − can fragment in a similar fashion to their protonated counterparts but, in addition, they may also dissociate via the cleavage of the N–C α and C α –C bonds of the peptide backbone to produce z-/c- and x-/a-type ions, with the exact pathway followed depending on the peptide sequence. ,− Side-chain cleavages at C α –C β and C β –C γ can also occur. − The richer fragmentation chemistry observed in the dissociation of a peptide radical cation provides additional information to that obtained from the fragmentation of the protonated peptide, potentially leading to a higher degree of certainty in the peptide sequencing.…”