Non‐zwitterionic structures of aliphatic‐only peptides mediated the formation and dissociation of gas phase radical cations

Abstract

We have investigated how the non-zwitterionic and zwitterionic structures of aliphatic-only tripeptides affect the formation and dissociation of peptide radical cations in the gas phase. The non-zwitterionic forms of the aliphatic-only peptides in their metal complexes play an important role in determining whether the electron transfer pathway predominates. We extended this study by synthesizing permanent non-zwitterionic and zwitterionic forms of aliphatic-only peptide radical cations and exploring their reactivities in the gas phase. Collision-induced dissociation spectra demonstrated the feasibility of generating both non-zwitterionic and zwitterionic forms. Radical cations in zwitterionic forms may indeed mediate the beta and gamma carbon-carbon bond cleavages of leucine and isoleucine side chains from the GlyGlyXle radical peptides; this feature allows leucine and isoleucine residues to be distinguished unambiguously.

Fragmentation ofα-radical cations of arginine-containing peptides

“…Peptide radical cations were produced through gas-phase fragmentation of ternary [Co III (salen)-peptide] ϩ complexes generated in the ESI source (Scheme 2, reactions 1 and 2). (We note parenthetically that while the properties of the metal and the organic ligand can be tuned to generate radical cations of aliphatic peptides [21], the presence of Y, W, and basic residues in peptide sequence facilitate the formation of M ϩ· ions [17][18][19][20][21][22][23].) In this study, peptide ␣-radicals were produced either directly by collision-induced dissociation (CID) of the [Co III (salen)-peptide] ϩ ion or by sequential fragmentation of isolated M ϩ· ions.…”

“…M ϩ· ions can be produced via gas-phase fragmentation of specially designed precursors. For example, radical cations of peptides without additional H atoms are produced by collision-induced dissociation (CID) of ternary metal-ligand-peptide complexes [17][18][19][20][21][22][23][24][25]. In addition, M ϩ· peptide ions have been generated through free radical-initiated reactions [26,27], CID of nitrosopeptides [28], and peptides containing labile serine and homoserine nitrate esters [29], photolysis of peptides containing iodinated tyrosine residues [30,31], and photodissociation of protonated peptides [32,33].…”

Fragmentation of Singly, Doubly, and Triply Charged Hydrogen Deficient Peptide Radical Cations in Infrared Multiphoton Dissociation and Electron Induced Dissociation

“…A frequently used method for generation of hydrogen deficient species is based on low energy CID of ternary metal complexes containing an auxiliary ligand (L) and the peptide or amino acid (M), [Metal(L)M] n+ [15][16][17][18][19][20][21][22][23][24][25][26]. Under low energy CID, dissociation of the [Metal(L)M] n+ complex is observed and the metal-auxiliary ligand system removes an electron from the departing peptide resulting in the generation of the hydrogen deficient species [18,21,27].…”

Experimental and computational studies of the macrocyclic effect of an auxiliary ligand on electron and proton transfers within ternary copper(II)-Histidine complexes

“…Oxidized radical products from Cu(II)-protein ion complexes have been proposed as intermediates that play key roles in several neurodegenerative conditions, including Alzheimer's disease (␤-amyloid peptide) and bovine spongiform encephalitis (prion protein) [3,4]. It was demonstrated recently that the dissociation of ligated Cu(II)-peptide complexes [Cu II (L)M] •2ϩ (L, ligand; M, peptide) generates peptide radical cations (M •ϩ ) through ET dissociation in the gas phase [7][8][9][10][11][12][13][14][15][16][17][18]. Such complexes are a useful simple system for studying the fundamental parameters that govern the formation of peptide radical cations through single-electron transfer in the absence of solvation.…”

“…In particular, we focused our efforts on the effects of macrocyclic auxiliary ligands on the competition between the ET and PT processes. To elucidate the mechanisms of peptide radical cation formation that arise from the macrocyclic effect of the auxiliary ligands, we attempted to further constrain the permanent non-zwitterionic structures of amino acids to rule out reactions arising from zwitterionic forms [17]. Our experimental approach involved maintaining the histidine fragment in its non-zwitterionic form within [Cu II (L)(His ϩ OMe)] •2ϩ complexes, where His ϩ OMe is the histidine methyl ester, which can exist only in its canonical (non-zwitterionic) form.…”