A Mass Spectrometric Approach for Probing the Stability of Bioorganic Radicals

Tan, Lei; Hu, Hanfeng; Francisco, Joseph S.; Xia, Yu

doi:10.1002/ange.201310480

Cited by 8 publications

(13 citation statements)

References 22 publications

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“…Ozonolysis of cysteine-containing peptides also yields abundant odd-electron [MÀ2H+ O]C À ions (Table S3). Similar sulfinyl radicals have been reported from radical-driven cleavage of disulfide-linked peptides in the gas phase [12] and have also been detected as reactive intermediates in some biochemical transformations. [13] These labeling experiments together with known thermochemistry can be used to infer am echanism for free-radical formation in the ozonolysis of [CysÀH] À (Scheme 2).…”

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confidence: 74%

Radical Formation in the Gas‐Phase Ozonolysis of Deprotonated Cysteine

et al. 2015

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Although the deleterious effects of ozone on the human respiratory system are well-known, many of the precise chemical mechanisms that both cause damage and afford protection in the pulmonary epithelial lining fluid are poorly understood. As a key first step to elucidating the intrinsic reactivity of ozone with proteins, its reactions with deprotonated cysteine [Cys−H]− are examined in the gas phase. Reaction proceeds at near the collision limit to give a rich set of products including 1) sequential oxygen atom abstraction reactions to yield cysteine sulfenate, sulfinate and sulfonate anions, and significantly 2) sulfenate radical anions formed by ejection of a hydroperoxy radical. The free-radical pathway occurs only when both thiol and carboxylate moieties are available, implicating electron-transfer as a key step in this reaction. This novel and facile reaction is also observed in small cys-containing peptides indicating a possible role for this chemistry in protein ozonolysis. George N. Khairallah,[a] ‡ Alan T. Maccarone, [b] ‡ Huong T. Pham, [b] Timothy M. Benton, [a] Tony Ly, [b] Gabriel da Silva, [c] Stephen J. Blanksby, [d] * and Richard A. J. O'Hair, [a] * Abstract: Although the deleterious effects of ozone on the human respiratory system are well known, many of the precise chemical mechanisms that both cause damage and afford protection in the pulmonary epithelial lining fluid are poorly understood. As a key first step to elucidating the intrinsic reactivity of ozone with proteins, its reactions with deprotonated cysteine [Cys-H] -are examined in the gas phase. Reaction proceeds at near the collision limit to give a rich set of products including (i) sequential O atom abstraction reactions to yield cysteine sulfenate, sulfinate and sulfonate anions, and significantly (ii) sulfenate radical anions formed by ejection of a hydroperoxyl radical. The free radical pathway occurs only where both thiol and carboxylate moieties are available implicating electron-transfer as a key step in this reaction. This novel and facile reaction is also observed in small cys-containing peptides indicating a possible role for this chemistry in protein ozonolysis.

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confidence: 74%

Radical Formation in the Gas‐Phase Ozonolysis of Deprotonated Cysteine

et al. 2015

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“…This is consistent with the stabilization of the pertinent fragment ions, which are peptide C α radicals. , In addition, a clear trend of decreasing SOH loss was observed when the sulfinyl radical was moved away from the lysine residue. The absence of SOH loss in [ SO • CGGK+H] + (Figure c) is likely due to the more favorable CH 2 SO loss from captodative stabilization of its product by the N-terminal amine . Solution-phase HDX was performed so that the contribution from proton-induced SOH loss could be distinguished (SI Figure ).…”

Section: Results and Discussionsupporting

confidence: 78%

“…Because these sulfinyl radicals were all derived from DSP, they shared a generic structure (shown in Table ), in which the N-terminal −NH 2 group of cysteine was replaced by a hydrogen, denoted as n - SO • Cys–X. Upon CID, the SOH loss fragmentation channel was greatly promoted in n - SO • Cys–X systems, whereas the radical-induced CH 2 SO loss was suppressed because of the lack of a captodative effect in stabilizing the as-formed glycyl radical species . In order to differentiate the origin of the hydrogen in the SOH loss channel, a sulfinyl radical with deuterium labeling at the C α and C β of the cysteine residue (referred to as d 4 - n - SO • Cys–X) was employed.…”

Section: Results and Discussionmentioning

confidence: 99%

“…If these two channels can be identified and differentiated, it provides a means to experimentally interrogate how the local environment is affecting the dual reactivity of sulfinyl radicals in peptides or proteins. In this work, we utilized dipeptide sulfinyl radical systems in which the N-terminal −NH 2 group of cysteine is replaced by a hydrogen, referred to as n - SO • Cys–X, to maximize the SOH loss fragmentation channel . Mechanistic studies demonstrate that the SOH loss could be either radical- or proton-induced.…”

Section: Introductionmentioning

confidence: 99%

“…For example, in the case of N-acetylated cysteine sulfinyl radical ions, the charge-driven H 2 O loss from protonated sulfinyl radical is dominant. 15 Recently, we observed the loss of hydrosulfinyl radical (SOH or HSO) as another fragmentation channel unique to the sulfinyl radical from CID studies of peptide sulfinyl radical ions, 22,23 which was absent in single amino acid cysteine sulfinyl radicals. Given the dual chemical property of the sulfinyl radical, it is possible that SOH loss happens either through radical-induced hydrogen abstraction or proton-driven SOH dissociation.…”

Section: ■ Introductionmentioning

confidence: 99%

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Probing the Radical and Base Dual Properties of Peptide Sulfinyl Radicals via Mass Spectrometry

et al. 2014

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Heteroatom-centered radicals are known to play critical roles in atmospheric chemistry, organic synthesis, and biology. While most studies have focused on the radical reactivity such as hydrogen abstraction, the base properties of heteroatom-centered radicals have long been overlooked, despite the profound consequences, such as their ability to participate in hydrogen-bonding networks. In this study, we use the sulfinyl radical (-SO(•)) as a model to show that the dual properties of heteroatom-centered radicals, that is, their ability to function as a radical and a base, can coexist in peptides and be differentiated by examining the loss of hydrosulfinyl radical (SOH) upon unimolecular dissociation of the peptide sulfinyl radical ions in the gas phase. The loss of SOH can result from two channels; one involves hydrogen atom abstraction, which reflects the radical property; the other is initiated by proton transfer to the sulfinyl radical, manifesting its base property. Tuning of the two properties of peptide sulfinyl radicals can be achieved by varying the chemical properties of the neighboring functional groups, which demonstrates the influence of the local chemical environment on the behavior of the radical species. The experimental approach established in this study to probe the dual chemical property of the peptide sulfinyl radical can be potentially applied to studying other types of heteroatom-centered radical species of biological significance.

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Radical Formation in the Gas‐Phase Ozonolysis of Deprotonated Cysteine

et al. 2015

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Although the deleterious effects of ozone on the human respiratory system are well-known, many of the precise chemical mechanisms that both cause damage and afford protection in the pulmonary epithelial lining fluid are poorly understood. As a key first step to elucidating the intrinsic reactivity of ozone with proteins, its reactions with deprotonated cysteine [Cys−H]− are examined in the gas phase. Reaction proceeds at near the collision limit to give a rich set of products including 1) sequential oxygen atom abstraction reactions to yield cysteine sulfenate, sulfinate and sulfonate anions, and significantly 2) sulfenate radical anions formed by ejection of a hydroperoxy radical. The free-radical pathway occurs only when both thiol and carboxylate moieties are available, implicating electron-transfer as a key step in this reaction. This novel and facile reaction is also observed in small cys-containing peptides indicating a possible role for this chemistry in protein ozonolysis. [b] Timothy M. Benton, [a] Tony Ly, [b] Gabriel da Silva, [c] Stephen J. Blanksby, [d] * and Richard A. J. O'Hair, [a] * Abstract: Although the deleterious effects of ozone on the human respiratory system are well known, many of the precise chemical mechanisms that both cause damage and afford protection in the pulmonary epithelial lining fluid are poorly understood. As a key first step to elucidating the intrinsic reactivity of ozone with proteins, its reactions with deprotonated cysteine [Cys-H] -are examined in the gas phase. Reaction proceeds at near the collision limit to give a rich set of products including (i) sequential O atom abstraction reactions to yield cysteine sulfenate, sulfinate and sulfonate anions, and significantly (ii) sulfenate radical anions formed by ejection of a hydroperoxyl radical. The free radical pathway occurs only where both thiol and carboxylate moieties are available implicating electron-transfer as a key step in this reaction. This novel and facile reaction is also observed in small cys-containing peptides indicating a possible role for this chemistry in protein ozonolysis.

show abstract

A Mass Spectrometric Approach for Probing the Stability of Bioorganic Radicals

Cited by 8 publications

References 22 publications

Radical Formation in the Gas‐Phase Ozonolysis of Deprotonated Cysteine

Radical Formation in the Gas‐Phase Ozonolysis of Deprotonated Cysteine

Probing the Radical and Base Dual Properties of Peptide Sulfinyl Radicals via Mass Spectrometry

Radical Formation in the Gas‐Phase Ozonolysis of Deprotonated Cysteine

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