Mobile protons versus mobile radicals: Gas-phase unimolecular chemistry of radical cations of cysteine-containing peptides

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The structure and reactivity of the N-acetyl-cysteine radical cation and anion were studied using ion-molecule reactions, infrared multi-photon dissociation (IRMPD) spectroscopy, and density functional theory (DFT) calculations. The radical cation was generated by first nitrosylating the thiol of N-acetyl-cysteine followed by the homolytic cleavage of the S-NO bond in the gas phase. IRMPD spectroscopy coupled with DFT calculations revealed that for the radical cation the radical migrates from its initial position on the sulfur atom to the α-carbon position, which is 2.5 kJ mol -1 lower in energy. The radical migration was confirmed by time-resolved ion-molecule reactions. These results are in contrast with our previous study on cysteine methyl ester radical cation (Osburn et al., Chem. Eur. J. 2011, 17, 873-879) and the study by Sinha et al. for cysteine radical cation (Phys. Chem. Chem. Phys. 2010, 12, 9794-9800) where the radical was found to stay on the sulfur atom as formed. A similar approach allowed us to form a hydrogen-deficient radical anion of N-acetyl-cysteine, (M -2H)•-. IRMPD studies and ion-molecule reactions performed on the radical anion showed that the radical remains on the sulfur, which is the initial and more stable (by 63.6 kJ mol -1 ) position, and does not rearrange.

Section: Resultsmentioning

confidence: 80%

Section: •+mentioning

confidence: 99%

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

Osburn

Berden

O’Hair

et al. 2011

Self Cite

“…Fragmentation pathways of hydrogen-deficient species in ECD were distinct from those observed in CID, IRMPD, and EID of the same species [21]. In general, in CID, IRMPD, and EID of highly charged hydrogen-deficient species fragmentation is governed by a competition between radical and chargedriven processes [10][11][12][13][14][15]21]. Abundant amino acid sidechain losses, enhanced cleavages at aromatic residues, and formation of a-, b-, c-, y-, c-, and z-type ions are observed [5,16,[20][21][22].…”

Section: Discussionmentioning

confidence: 83%

“…Dissociation of hydrogen-deficient species is determined by the competition between radical and charge driven processes [10][11][12][13][14][15]. For singly charged arginine containing radical cations, M +• , dissociation is governed by radical driven processes resulting mainly in C a -C bond cleavages and side chain losses [12,13,16].…”

Section: Introductionmentioning

confidence: 99%

Electron Capture Dissociation of Hydrogen-Deficient Peptide Radical Cations

Kalli

Hess

2012

Hydrogen-deficient peptide radical cations exhibit fascinating gas phase chemistry, which is governed by radical driven dissociation and, in many cases, by a combination of radical and charge driven fragmentation. Here we examine electron capture dissociation (ECD) of doubly, • precursor ions resulted in efficient electron capture by the hydrogen-deficient species. However, the intensities of c-and z-type product ions were reduced, compared with those observed for the even electron species, indicating suppression of N-C α backbone bond cleavages. We postulate that radical recombination occurs after the initial electron capture event leading to a stable even electron intermediate, which does not trigger N-C α bond dissociations. Although the intensities of c-and z-type product ions were reduced, the number of backbone bond cleavages remained largely unaffected between the ECD spectra of the even electron and hydrogen-deficient species. We hypothesize that a small ion population exist as a biradical, which can trigger N-C α bond cleavages. Alternatively, radical recombination and N-C α bond cleavages can be in competition, with radical recombination being the dominant pathway and N-C α cleavages occurring to a lesser degree. Formation of b-and y-type ions observed for two of the hydrogendeficient peptides examined is also discussed.

“…Interestingly, RDD is not a charge dominated process, in contrast with most other gas-phase chemistry. The primary competition with RDD in positively charged peptides occurs when fully mobile protons exist, creating alternative low energy dissociation channels [27][28][29][30]. The absence of mobile protons is therefore potentially significant for RDD in anionic peptides.…”

mentioning

confidence: 99%

Dissociation Chemistry of Hydrogen-Deficient Radical Peptide Anions

Moore

Sun

Hsu

et al. 2011

The fragmentation chemistry of anionic deprotonated hydrogen-deficient radical peptides is investigated. Homolytic photodissociation of carbon-iodine bonds with 266 nm light is used to generate the radical species, which are subsequently subjected to collisional activation to induce further dissociation. The charges do not play a central role in the fragmentation chemistry; hence deprotonated peptides that fragment via radical directed dissociation do so via mechanisms which have been reported previously for protonated peptides. However, charge polarity does influence the overall fragmentation of the peptide. For example, the absence of mobile protons favors radical directed dissociation for singly deprotonated peptides. Similarly, a favorable dissociation mechanism initiated at the N-terminus is more notable for anionic peptides where the N-terminus is not protonated (which inhibits the mechanism). In addition, collisional activation of the anionic peptides containing carbon-iodine bonds leads to homolytic cleavage and generation of the radical species, which is not observed for protonated peptides presumably due to competition from lower energy dissociation channels. Finally, for multiply deprotonated radical peptides, electron detachment becomes a competitive channel both during the initial photoactivation and following subsequent collisional activation of the radical. Possible mechanisms that might account for this novel collision-induced electron detachment are discussed.