Leaving Group Effects in a Series of Electrosprayed CcHhN1 Anthracene Derivatives

Abutokaikah, Maha T.; Gnawali, Giri; Frye, Joseph W.; Stump, Curtis M.; Tschampel, John; Murphy, Matthew; Lachance, Eli S.; Guan, Shanshan; Spilling, Christopher D.; Bythell, Benjamin J.

doi:10.1007/s13361-019-02298-0

Cited by 2 publications

(4 citation statements)

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“…The phenylene spacer parts of the tag provide additional mass and stability by limiting proton mobility ,− (barriers >254 kJ mol –1 ) and thus prevent facile amide bond cleavages. The transformation from untagged analytes with a single negative charge to tagged analytes with multiple positive charges with piperidine tags results in fragmentation across the C–C backbone rather than uninformative neutral losses.…”

Section: Resultsmentioning

confidence: 99%

“…Additionally, this tagging produces predictable fragmentation, often along the C–C backbone of the metabolite. We complement our LC–MS/MS separation and fragmentation of these analytes with computational modeling − of the key dissociation processes. The resulting predictive capacity can then be applied more broadly for subsequent identification of unknown metabolites.…”

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confidence: 99%

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Isomeric Differentiation and Acidic Metabolite Identification by Piperidine-Based Tagging, LC–MS/MS, and Understanding of the Dissociation Chemistries

et al. 2020

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We demonstrate a method for facile differentiation of acidic, isomeric metabolites by attaching high proton affinity, piperidine-based chemical tags to each carboxylic acid group. These tags attach with high efficiency to the analytes, increase the signal, and result in the formation of multiply-charged cations. We illustrate the present approach with citrate and isocitrate, which are isomeric metabolites each containing three carboxylic acid groups. We observe a 20-fold increase in signal-to-noise for citrate and an 8fold increase for isocitrate as compared to detection of the untagged analytes in negative mode. Collision-induced dissociation of the triply tagged, triply charged analytes results in distinct tandem mass spectra. The phenylene spacer groups limit proton mobility and enable access to structurally informative C−C bond cleavage reactions. Modeling of the gas-phase structures and dissociation chemistry of these triply charged analyte ions highlights the importance of hydroxyl proton mobilization in this low proton mobility environment. Tandem mass spectrometric analyses of deuterated congeners and MS 3 spectra are consistent with the proposed fragment ion structures and mechanisms of formation. Direct evidence that these chemistries are more generally applicable is provided by subsequent analyses of doubly tagged, doubly charged malate ions. Future work will focus on applying these methods to identify new metabolites and development of general rules for structural determination of tagged metabolites with multiple charges.

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Isomeric Differentiation and Acidic Metabolite Identification by Piperidine-Based Tagging, LC–MS/MS, and Understanding of the Dissociation Chemistries

et al. 2020

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“…For the [AT(GalNAc)A+H] + ions, the lowest-energy mechanism involves isomerization , prior to glycosidic bond dissociation (Scheme ). This pathway begins with the mobilization of the ionizing proton to the carbonyl oxygen of the N-terminal alanine.…”

Section: Resultsmentioning

confidence: 99%

“…Consistent with the wider understanding of peptide dissociation chemistry, the key difference is which fragment keeps the ionizing proton. 63−65 For the [AT(GalNAc)A+H] + ions, the lowest-energy mechanism involves isomerization 22,66 prior to glycosidic bond dissociation (Scheme 2). This pathway begins with the mobilization of the ionizing proton to the carbonyl oxygen of the N-terminal alanine.…”

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Protonated α-N-Acetyl Galactose Glycopeptide Dissociation Chemistry

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Guan

Schultz

et al. 2022

J. Am. Soc. Mass Spectrom.

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We recently provided mass spectrometric, H/D labeling, and computational evidence of pyranose to furanose N-acetylated ion isomerization reactions that occurred prior to glycosidic bond cleavage in both O- and N-linked glycosylated amino acid model systems (Phys. Chem. Chem. Phys.2021232325623266). These reactions occurred irrespective of the glycosidic linkage stereochemistry (α or β) and the N-acetylated hexose structure (GlcNAc or GalNAc). In the present article, we test the generality of the preceding findings by examining threonyl α-GalNAc-glycosylated peptides. We utilize computational chemistry to compare the various dissociation and isomerization pathways accessible with collisional activation. We then interrogate the structure(s) of the resulting charged glycan and peptide fragments with infrared “action” spectroscopy. Isomerization of the original pyranose, the protonated glycopeptide [AT(GalNAc)A+H]+, is predicted to be facile compared to direct dissociation, as is the glycosidic bond cleavage of the newly formed furanose form, i.e., furanose oxazolinium ion structures are predicted to predominate. IR action spectra for the m/z 204, C8H14N1O5 +, glycan fragment population support this prediction. The IR action spectra of the complementary m/z 262 peptide fragment were assigned as a mixture of the lowest-energy structures of [ATA+H]+ consistent with the literature. If general, the change to a furanose m/z 204 product ion structure fundamentally alters the ion population available for MS3 dissociation and glycopeptide sequence identification.

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Leaving Group Effects in a Series of Electrosprayed C_cH_hN₁ Anthracene Derivatives

Cited by 2 publications

References 85 publications

Isomeric Differentiation and Acidic Metabolite Identification by Piperidine-Based Tagging, LC–MS/MS, and Understanding of the Dissociation Chemistries

Isomeric Differentiation and Acidic Metabolite Identification by Piperidine-Based Tagging, LC–MS/MS, and Understanding of the Dissociation Chemistries

Protonated α-N-Acetyl Galactose Glycopeptide Dissociation Chemistry

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