Ion–molecule reactions reveal facile radical migration in peptides

Moore, Benjamin; Blanksby, Stephen J.; Julian, Ryan R.

doi:10.1039/b907833a

Cited by 56 publications

(62 citation statements)

References 33 publications

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“…Such behavior has been previously characterized for radical z ions produced by ECD as well as in hydrogen-deficient radicals formed by photodissociation. [14][15] Similar experiments were performed on the major product ions observed by FRIPS of AARAAASAA, and the [a 6 +H] • , c 6 , and a 7 ions gave spectra nearly identical to those obtained for AARAAATAA. Collisional activation of the neutral loss of CO 2 resulted in a spectrum similar to the initial FRIPS spectrum, indicating that further hydrogen-deficient radical chemistry dominated in the dissociation of this ion (data not shown).…”

Section: Analysis Of Frips Product Ions In Serine/threonine Peptides supporting

confidence: 62%

Hydrogen Bonding Constrains Free Radical Reaction Dynamics at Serine and Threonine Residues in Peptides

et al. 2014

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Synthesis of TEMPO-based FRIPS reagent. Scheme S1. Synthesis method for FRIPS reagentThe synthesis strategy for the second generation TEMPO-based FRIPS reagent (10) is summarized in Scheme S1. The previous development by Lee et al. 1 was modified by replacing 2-(bromomethyl)benzoic acid methyl ester with methyl 2-bromoacetate for the current study, as outlined briefly previously. 2 Further details are given here. Methyl 2-(2,2,6,6-tetramethylpiperidin-1-yloxy)acetate (ii)A 25 mL, 3-neck flask equipped with a teflon-coated, oval shaped magnetic bar was flamebaked under vacuum, charged with dry N 2 gas, and cooled down to room temperature. To the flask was added methyl 2-bromoacetate (i) (0.474 mL, 5 mmol, 1 equiv), TEMPO (957 mg,6 mmol, 1.2 equiv), Cu(OTf) 2 (185 mg, 0.5 mmol, 0.1 equiv), copper powder (318mg, 5 mmol, 1 equiv), 4,4′-dinonyl-2,2′-bipyridyl (Nbpy, 843 mg, 0.4 equiv), and benzene (10 mL, 0.5 M). The reaction mixture was degassed by bubbling dry N 2 gas and stirred at 70 °C for 15 h under a stream of dry N 2 gas while monitoring conversion by thin layer chromatography (hexane : ethyl 3 acetate = 10 : 1, KMnO 4 ). The crude mixture was cooled down to room temperature, briefly cleaned by filtration through a short pad of silica gel, and the silica gel pad was thoroughly washed by ethyl acetate (EtOAc) to recover the product. The filtrate was washed by saturated NH 4 Cl, and 1 M NH 4 OH to remove the residual copper ions. The organic layer was further washed by saturated brine, dried over anhydrous MgSO 4 , concentrated by a rotavap, and purified by silica gel column chromatography (hexane : EtOAc = 20 : 1). The desired product, methyl 2-(2,2,6,6-tetramethylpiperidin-1-yloxy)acetate (ii) (1.023g, 4.46 mmol) was obtained as a yellow 2-(2,2,6,6-tetramethylpiperidin-1-yloxy)acetic acid (iii)To a 25 mL, one-neck flask was added methyl 2-(2,2,6,6-tetramethylpiperidin-1-yloxy)acetate (ii) (246 mg, 1.07 mmol, 1 equiv), tetrahydrofuran (THF) (5 mL), and 2 M Potassium Hydroxide (KOH, 5 mL). The mixture was stirred at room temperature for 24 h. The reaction was monitored by thin layer chromatography and ESI-MS until the starting material was completely consumed.Upon completion of the reaction, THF was removed by rotavap, and the residual aqueous layer was neutralized by ~5 mL of 2 M HCl to yield a pH of ~6. The mixture was extracted by CH 2 Cl 2 (×5), and the combined organic layer was dried over anhydrous MgSO 4 , concentrated by rotavap, and purified by silica gel column chromatography (hexane : EtOAc = 2 : 1) to yield 2-(2,2,6,6-tetramethylpiperidin-1-yloxy)acetic acid (iii) (137 mg, 0.635 mmol) as a white powder. Yield: 10, 75.53, 59.86, 39.59, 32.82, 20.31, 16.99. 2,5-dioxopyrrolidin-1-yl 2-(2,2,6,6-tetramethylpiperidin-1-yloxy)acetate (iv)In a flame-baked 50 mL one neck flask, N-hydroxysuccinimide (2.75 g) was added to 14 mL of trifluoroacetic anhydride at room temperature under a stream of dry N 2 gas and stirred for 4 h.The solvent was removed by rotavap and further eliminated by high vacuum overnight....

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Section: Analysis Of Frips Product Ions In Serine/threonine Peptides supporting

confidence: 62%

Hydrogen Bonding Constrains Free Radical Reaction Dynamics at Serine and Threonine Residues in Peptides

et al. 2014

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“…The excess energy is distributed between the internal and the kinetic-energyrelease of the fragments. However, we cannot exclude that in MS 3 experiments, collisional excitation may allow radical migration before fragmentation, as recently evidenced [38].…”

Section: Vuv Electron Detachment On Polypeptide Ionsmentioning

confidence: 99%

Formation and Fragmentation of Radical Peptide Anions: Insights from Vacuum Ultra Violet Spectroscopy

Brunet

Antoine

Dugourd

et al. 2011

J. Am. Soc. Mass Spectrom.

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We have studied the photodissociation of gas-phase deprotonated caerulein anions by vacuum ultraviolet (VUV) photons in the 4.5 to 20 eV range, as provided by the DESIRS beamline at the synchrotron radiation facility SOLEIL (France). Caerulein is a sulphated peptide with three aromatic residues and nine amide bonds. Electron loss is found to be the major relaxation channel at every photon energy. However, an increase in the fragmentation efficiency (neutral losses and peptide backbone cleavages) as a function of the energy is also observed. The oxidized ions, generated by electron photodetachment were further isolated and activated by collision (CID) in a MS 3 scheme. The branching ratios of the different fragments observed by CID as a function of the initial VUV photon energy are found to be independent of the initial photon energy. Thus, there is no memory effect of the initial excitation energy on the fragmentation channels of the oxidized species on the time scale of our tandem MS experiment. We also report photofragment yields as a function of photon energy for doubly deprotonated caerulein ions, for both closed-shell ([M -2H] 2-) non-radical ions and open-shell ([M -3H] 2-• ) radical ions. These latter ions are generated by electron photodetachment from [M -3H] 3-precursor ions. The detachment yield increases monotonically with the energy with the appearance of several absorption bands. Spectra for radical and non-radical ions are quite similar in terms of observed bands; however, the VUV fragmentation yield is enhanced by the presence of a radical in caerulein peptides.

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“…Loss of 57 Da was also observed in the CID spectrum of the z 3 ion where it formed the m/z 244 fragment ion (Figure 5b). These backbone fragments formally correspond to (y n -2H) ions (n=1-3), and their formation can be visualized by radical-induced reactions involving H-atom migrations analogous to those reported previously for other peptide cation-radicals [40][41][42][43][44][45]. CID of the z 2 ion results in decarboxylation (m/z 186) and Arg side-chain cleavage (m/z 100) which both are likely to be radical-driven [41].…”

Section: Non-phosphorylated Z Ionsmentioning

confidence: 99%

Dipole-Guided Electron Capture Causes Abnormal Dissociations of Phosphorylated Pentapeptides

Moss

Chung

Wyer

et al. 2011

J. Am. Soc. Mass Spectrom.

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Electron transfer and capture mass spectra of a series of doubly charged ions that were phosphorylated pentapeptides of a tryptic type (pS,A,A,A,R) showed conspicuous differences in dissociations of charge-reduced ions. Electron transfer from both gaseous cesium atoms at 100 keV kinetic energies and fluoranthene anion radicals in an ion trap resulted in the loss of a hydrogen atom, ammonia, and backbone cleavages forming complete series of sequence z ions. Elimination of phosphoric acid was negligible. In contrast, capture of lowenergy electrons by doubly charged ions in a Penning ion trap induced loss of a hydrogen atom followed by elimination of phosphoric acid as the dominant dissociation channel. Backbone dissociations of charge-reduced ions also occurred but were accompanied by extensive fragmentation of the primary products. z-Ions that were terminated with a deaminated phosphoserine radical competitively eliminated phosphoric acid and H 2 PO 4 radicals. A mechanism is proposed for this novel dissociation on the basis of a computational analysis of reaction pathways and transition states. Electronic structure theory calculations in combination with extensive molecular dynamics mapping of the potential energy surface provided structures for the precursor phosphopeptide dications. Electron attachment produces a multitude of low lying electronic states in charge-reduced ions that determine their reactivity in backbone dissociations and H-atom loss. The predominant loss of H atoms in ECD is explained by a distortion of the Rydberg orbital space by the strong dipolar field of the peptide dication framework. The dipolar field steers the incoming electron to preferentially attach to the positively charged arginine side chain to form guanidinium radicals and trigger their dissociations.

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Ion–molecule reactions reveal facile radical migration in peptides

Abstract: Ion-molecule reactions between molecular oxygen and peptide radicals in the gas phase demonstrate that radical migration occurs easily within large biomolecules without addition of collisional activation energy.

Cited by 56 publications

References 33 publications

Hydrogen Bonding Constrains Free Radical Reaction Dynamics at Serine and Threonine Residues in Peptides

Hydrogen Bonding Constrains Free Radical Reaction Dynamics at Serine and Threonine Residues in Peptides

Formation and Fragmentation of Radical Peptide Anions: Insights from Vacuum Ultra Violet Spectroscopy

Dipole-Guided Electron Capture Causes Abnormal Dissociations of Phosphorylated Pentapeptides

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