Formation of Anionic Peptide Radicals In Vacuo

Abstract

In this paper, we demonstrate for the first time the formation of radical anionic peptides [M - 2H]*- through a one-electron transfer mechanism upon low-energy collision-induced dissociation (CID) of gas-phase singly charged [Mn(III)(salen)(M - 2H)]*- complex ions [where salen is N,N'-ethylenebis(salicylideneiminato) and M is an angiotensin III derivative]. The types of fragment ions formed from [M - 2H]*- share some similarities with those from the cationic radical peptides M*+ and [M + H]*2+, but differ significantly from those of the corresponding deprotonated peptides [M - H]-. Fragmentation of [M - 2H]*- radical anionic angiotensin III derivatives leads preferentially to product ions of side-chain cleavage of amino acid residues, z-type and minor x-type fragment ions, most of which are types rarely observed in low-energy CID spectra of deprotonated analogs. The degree of competitive dissociation of the complexes is highly dependent on the nature of the substituted salen derivatives. The yields of anionic peptide radicals were enhanced to the greatest extent when electron withdrawing groups were positioned at the 5 and 5' positions, but the effect was rather modest when such groups resided at the 3 and 3' positions. Substituting a cyclohexyl unit of a salen with phenyl or naphthyl moieties at the 8 and 8' positions also facilitated electron-transfer pathways.

Gas-Phase Peptide Sulfinyl Radical Ions: Formation and Unimolecular Dissociation

“…Note that before applying the plasma, only intact peptide ions could be observed from nanoESI. When the LTP plasma and the nanoESI were both functioning, the formation of sulfhydryl (−SH) and sulfinyl radical (−SO•) from each peptide chain, notated as [ fewer studies have been done on peptide radical anions primarily due to limited ways of generating them in gas phase [38][39][40]42]. As shown in Figure 1b, peptide sulfinyl radical anions could be generated simply by switching the ionization mode from positive to negative since the reactions are induced by radicals.…”

“…Hydrogen deficient cations can be generated by a variety of methods: laser ablation followed by ultraviolet (UV) photoionization [22,23]; collision-induced dissociation (CID) of metal-ligand-peptide complexes [24][25][26]; CID of peptide derivatives with labile bonds such as S-nitrosylation [27,28], serine/homoserine nitrate esters [29], peroxycarbamates [30], 2,2,6,6-tetramethylpiperidine-1-oxy (TEMPO) [31,32], and 4,4'-azobis(4-cyanopentanoic acid) (Vazo 68) [33]; UV photolysis of iodinated tyrosine containing peptides [34]; or noncovalent complexes with photolabile precursor [35]; electroninduced dissociation of multiply charged ions [36,37]. Hydrogen deficient radical anions can be formed by electron detachment [38] or photodetachment [39] from multiply deprotonated molecules, CID of peptide-metal complexes [40,41], and photodissociation of iodinated peptide [42].…”

Structure and Reactivity of theN-Acetyl-Cysteine Radical Cation and Anion: Does Radical Migration Occur?

“…Exceptions include Chu and coworkers' use of ternary metal complexes [42,43] and the use of ion-ion reactions between multiply deprotonated peptides and cations [44]. Being able to generate peptide radical anions is equally important, as many peptides are negatively charged in solution.…”

Dissociation Chemistry of Hydrogen-Deficient Radical Peptide Anions

“…The fragmentation pathways and chemistry of positively charged hydrogendeficient radicals have been studied extensively [17][18][19][20][21][22][23][24]. Hydrogen-deficient radical anions have been neglected by comparison [25,26]. Interestingly, RDD is not a charge dominated process, in contrast with most other gas-phase chemistry.…”