Use of transition metals to improve the diastereomers differentiation by ion mobility and mass spectrometry

Domalain, Virginie; Hubert‐Roux, Marie; Lange, Catherine; Baudoux, Jérôme; Rouden, Jacques; Afonso, Carlos

doi:10.1002/jms.3349

Cited by 24 publications

(22 citation statements)

References 19 publications

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“…38 More recently, the formation of multimers and metal ion adducts to diastereomeric small molecules was used to improve the isomeric resolution observed in TWIMS-MS experiments. 14,32 Stabilization of salt-bridge and charge-solvated amino acid geometries in the gas-phase with alkali metal ions has been extensively studied with infrared multiple photon dissociation (IRMPD) spectroscopy, and metal ion size has been shown to be a significant factor in the stabilization of a given structure. 47-56 While IRMPD has been the primary tool to evaluate amino acid gas-phase geometries in the past, it is particularly interesting to investigate whether salt-bridge or charge-solvated forms for different 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 6 isomeric species can be elucidated with TWIMS analysis.…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, several mass spectrometric strategies for distinguishing isomeric species using mass spectrometry have been developed, including the kinetic method based on the dissociation of cluster ions, 12,22 collision induced dissociation of diastereomeric adducts, 23,27 host-guest ion molecule reactions, [23][24][25][26][28][29] and ion mobility analysis. [12][13][14][15][16][17][18][19][20][30][31][32][33][34][35][36][37] Ion mobility spectrometry (IMS) has the ability to rapidly separate isomeric species based on their mobilities through a drift gas under the influence of an electric field, which depends primarily on the shape and charge of the gas-phase ion. The IMS-MS combination has therefore provided a proven mechanism for the gas-phase separation and characterization of isomers and conformers ranging from small 5 molecules 31,33,36,38 and amino acids 16,33,39 to proteins 40-42 and large native protein complexes.…”

Section: Introductionmentioning

confidence: 99%

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Structural Resolution of 4-Substituted Proline Diastereomers with Ion Mobility Spectrometry via Alkali Metal Ion Cationization

2015

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The chirality of substituents on an amino acid can significantly change its mode of binding to a metal ion, as shown here experimentally by traveling wave ion mobility spectrometry-mass spectrometry (TWIMS-MS) of different proline isomeric molecules complexed with alkali metal ions. Baseline separation of the cis- and trans- forms of both hydroxyproline and fluoroproline was achieved using TWIMS-MS via metal ion cationization (Li(+), Na(+), K(+), and Cs(+)). Density functional theory calculations indicate that differentiation of these diastereomers is a result of the stabilization of differing metal-complexed forms adopted by the diastereomers when cationized by an alkali metal cation, [M + X](+) where X = Li, Na, K, and Cs, versus the topologically similar structures of the protonated molecules, [M + H](+). Metal-cationized trans-proline variants exist in a linear salt-bridge form where the metal ion interacts with a deprotonated carboxylic acid and the proton is displaced onto the nitrogen atom of the pyrrolidine ring. In contrast, metal-cationized cis-proline variants adopt a compact structure where the carbonyl of the carboxylic acid, nitrogen atom, and if available, the hydroxyl and fluorine substituent solvate the metal ion. Experimentally, it was observed that the resolution between alkali metal-cationized cis- and trans-proline variants decreases as the size of the metal ion increases. Density functional theory demonstrates that this is due to the decreasing stability of the compact charge-solvated cis-proline structure with increased metal ion radius, likely a result of steric hindrance and/or weaker binding to the larger metal ion. Furthermore, the unique structures adopted by the alkali metal-cationized cis- and trans-proline variants results in these molecules having significantly different quantum mechanically calculated dipole moments, a factor that can be further exploited to improve the diastereomeric resolution when utilizing a drift gas with a higher polarizability constant.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Structural Resolution of 4-Substituted Proline Diastereomers with Ion Mobility Spectrometry via Alkali Metal Ion Cationization

2015

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“…The fixed ligands chosen were L-Phe -Gly, 5′CMP, and 5′GMP, based on previous literature [41,[46][47][48]. Fixed ligands must contain some inherent chirality and, preferably, an aromatic group that could increase chiral discrimination from cation-π interactions with the central, divalent metal cation [32,46,47]. More specifically, the exact combinations were: Mn aldohexoses was determined, the next step was to apply those same conditions to the eight ketohexoses.…”

Section: Aldohexoses-fixed Ligand Kinetic Methodsmentioning

confidence: 99%

“…However, mass spectrometry has certain inherent advantages compared with the aforementioned analytical techniques previously employed for monosaccharide analysis [1, 17, Figure 1. The 24 hexose monosaccharide isomers 18,22,31,32]. Specifically, mass spectrometry does not require any solvent or stationary phase, and also provides fast, accurate, and sensitive sample analysis.…”

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confidence: 99%

Complete Hexose Isomer Identification with Mass Spectrometry

Nagy

Pohl

2015

J. Am. Soc. Mass Spectrom.

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Abstract. The first analytical method is presented for the identification and absolute configuration determination of all 24 aldohexose and 2-ketohexose isomers, including the D and L enantiomers for allose, altrose, galactose, glucose, gulose, idose, mannose, talose, fructose, psicose, sorbose, and tagatose. Two unique fixed ligand kinetic method combinations were discovered to create significant enough energetic differences to achieve chiral discrimination among all 24 hexoses. Each of these 24 hexoses yields unique ratios of a specific pair of fragment ions that allows for simultaneous determination of identification and absolute configuration. This mass spectrometric-based methodology can be readily employed for accurate identification of any isolated monosaccharide from an unknown biological source. This work provides a key step towards the goal of complete de novo carbohydrate analysis.

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“…Proposed mechanisms for the release of ammonia (a) alone or together with acrylic acid from the ammonium adduct of α-Glu-5A (with NH 4 + on acrylate at C2); (b) alone from the ammonium adduct of β-Glu-5A (with NH 4 + on acrylate at C1) separate the two anomers. Indeed, besides its ability to distinguish conformers, TWIMS is also powerful at separating structural isomers of small gas phase ions, as reported for anomers and epimers of monosaccharide methyl glycosides [42], cistrans isomers of terpyridine derivatives [43], as well as a variety of diastereoisomers [44][45][46][47]. The DMAC and THF samples were subjected to ESI-TWIMS-MS experiments where all ions generated during electrospray were injected into the TWIMS cell prior to be mass analyzed in the oa-TOF mass analyzer.…”

Section: Cid Of [Glu-na + Nh 4 ]mentioning

confidence: 99%

Anomerization of Acrylated Glucose During Traveling Wave Ion Mobility Spectrometry

Chendo

Moreira

Tintaru

et al. 2015

J. Am. Soc. Mass Spectrom.

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Abstract. Anomerization of simple sugars in the liquid phase is known as an acidand base-catalyzed process, which highly depends on solvent polarity. This reaction is reported here to occur in the gas phase, during traveling wave ion mobility spectrometry (TWIMS) experiments aimed at separating α-and β-anomers of penta-acrylated glucose generated as ammonium adducts in electrospray ionization. This compound was available in two samples prepared from glucose dissolved in solvents of different polarity, namely tetrahydrofuran (THF) and N,Ndimethylacetamide (DMAC), and analyzed by electrospray tandem mass spectrometry (ESI-MS/MS) as well as traveling wave ion mobility (ESI-TWIMS-MS). In MS/MS, an anchimerically-assisted process was found to be unique to the electrosprayed α-anomer, and was only observed for the THF sample. In ESI-TWIMS-MS, a signal was measured at the drift time expected for the α-anomer for both the THF and DMAC samples, in apparent contradiction to the MS/MS results, which indicated that the α-anomer was not present in the DMAC sample. However, MS/MS experiments performed after TWIMS separation revealed that ammonium adducts of the α-anomer produced from each sample, although exhibiting the same collision cross section, were clearly different. Indeed, while the α-anomer actually present in the THF sample was electrosprayed with the ammonium adducted at the C2 acrylate, its homologue only observed when the DMAC sample was subjected to TWIMS hold the adducted ammonium at the C1 acrylate. These findings were explained by a β/α inter-conversion upon injection in the TWIMS cell, as supported by theoretical calculation and dynamic molecular modeling.

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Use of transition metals to improve the diastereomers differentiation by ion mobility and mass spectrometry

Cited by 24 publications

References 19 publications

Structural Resolution of 4-Substituted Proline Diastereomers with Ion Mobility Spectrometry via Alkali Metal Ion Cationization

Structural Resolution of 4-Substituted Proline Diastereomers with Ion Mobility Spectrometry via Alkali Metal Ion Cationization

Complete Hexose Isomer Identification with Mass Spectrometry

Anomerization of Acrylated Glucose During Traveling Wave Ion Mobility Spectrometry

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