Protomers of Benzocaine: Solvent and Permittivity Dependence

Warnke, Stephan; Seo, Jongcheol; Boschmans, Jasper; Sobott, Frank; Scrivens, James H.; Bleiholder, Christian; Bowers, Michael T.; Gewinner, Sandy; Schöllkopf, Wieland; Pagel, Kevin; Helden, Gert von

doi:10.1021/jacs.5b01338

Cited by 202 publications

(356 citation statements)

References 33 publications

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“…More recently, various forms of ion mobility have separated tautomers prior to subsequent MS analysis [16][17][18][19]. Among these examples, we described the use of differential mobility spectrometry (DMS) [20][21][22][23][24] to separate the tautomers of protonated 4-ABA (N-and O-protonated) [25].…”

Section: Introductionmentioning

confidence: 99%

“…Using reactions with D 2 O, CH 3 OD, and their un-enriched analogues (i.e., H 2 O, CH 3 OH), we detail how DMS can identify when tautomerization occurs during gas-phase HDX. Although other forms of ion mobility have been employed to separate tautomers [16][17][18][19], DMS has some unique advantages for probing such elusive species. For example, DMS has the ability to separate ions based upon subtle differences in their interactions with solvent molecules [22,24,40] (and not collision cross section alone); in addition, the relative ease of modifying experimental configurations with rapid change-over of diagnostic ion/molecule reactions (e.g., switch from D 2 O to H 2 O, etc.…”

Section: Introductionmentioning

confidence: 99%

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Studying Gas-Phase Interconversion of Tautomers Using Differential Mobility Spectrometry

Campbell

Yang

Melo

et al. 2016

J. Am. Soc. Mass Spectrom.

125

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Abstract. In this study, we report on the use of differential mobility spectrometry (DMS) as a tool for studying tautomeric species, allowing a more in-depth interrogation of these elusive isomers using ion/molecule reactions and tandem mass spectrometry. As an example, we revisit a case study in which gas-phase hydrogendeuterium exchange (HDX)-a probe of ion structure in mass spectrometry-actually altered analyte ion structure by tautomerization. For the N-and O-protonated tautomers of 4-aminobenzoic acid, when separated using DMS and subjected to subsequent HDX with trace levels of D 2 O, the anticipated difference between the exchange rates of the two tautomers is observed. However, when using higher levels of D 2 O or a more basic reagent, equivalent and almost complete exchange of all labile protons is observed. This second observation is a result of the interconversion of the N-protonated tautomer to the Oprotonated form during HDX. We can monitor this transformation experimentally, with support from detailed molecular dynamics and electronic structure calculations. In fact, calculations suggest the onset of bulk solution phase properties for 4-aminobenzoic acid upon solvation with eight CH 3 OH molecules. These findings also underscore the need for choosing HDX reagents and conditions judiciously when separating interconvertible isomers using DMS.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Studying Gas-Phase Interconversion of Tautomers Using Differential Mobility Spectrometry

Campbell

Yang

Melo

et al. 2016

J. Am. Soc. Mass Spectrom.

125

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“…Experiments were performed on an in-house constructed drifttube ion mobility-mass spectrometer (IM-MS) similar to one described previously [12,16]. Briefly, ions are brought into the gas phase using nano-electrospray ionization (nESI) and are transferred into the vacuum of the instrument.…”

Section: Ion Mobility Spectrometrymentioning

confidence: 99%

“…Instead, these extended structures are characterized by a regular and highly ordered network of intramolecular C5-type hydrogen bonds between adjacent N-H and C=O groups ( Figure 1). Using a combination of ion mobility-mass spectrometry (IM-MS) and gasphase IRMPD spectroscopy [12], we here shed further light on the gas-phase unzipping of highly charged ions. In particular, we investigate the impact of the initial secondary structure and the location of basic amino acid residues within the molecule.…”

mentioning

confidence: 99%

From Compact to String—The Role of Secondary and Tertiary Structure in Charge-Induced Unzipping of Gas-Phase Proteins

Warnke

Hoffmann

Seo

et al. 2016

J. Am. Soc. Mass Spectrom.

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In the gas phase, protein ions can adopt a broad range of structures, which have been investigated extensively in the past using ion mobility-mass spectrometry (IM-MS) based methods. Compact ions with low number of charges undergo a Coulomb-driven transition to partially folded species when the charge increases and finally form extended structures with presumably little or no defined structure when the charge state is high. However, with respect to the secondary structure, IM-MS methods are essentially blind. Infrared (IR) spectroscopy, on the other hand, is sensitive to such structural details and there is increasing evidence that helices as well as β-sheet-like structures can exist in the gas phase, especially for ions in low charge states. Very recently, we showed that also the fully extended form of highly charged protein ions can adopt a distinct type of secondary structure that features a characteristic C5-type hydrogen bond pattern. Here we use a combination of IM-MS and IR spectroscopy to further investigate the influence of the initial, native conformation on the formation of these structures. Our results indicate that when intramolecular Coulomb-repulsion is large enough to overcome the stabilization energies of the genuine secondary structure, all proteins, regardless of their sequence or native conformation, form C5-type hydrogen bond structures. Furthermore, our results suggest that in highly charged proteins the positioning of charges along the sequence is only marginally influenced by the basicity of individual residues.In the gas-phase environment of a mass spectrometer, proteins can adopt a broad range of distinct structures. When electrosprayed from native, buffered solutions especially large proteins and protein complexes are known to retain features of their condensed-phase conformation -a fact that found broad application in the field of native mass spec-

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“…Particular interest recently focused on the phenomenon of alternative charge sites in small molecules that are observed in the gas phase, i.e. the observation of protonation site isomers (protomers) [24][25][26]. The routine use as a separation technique is however still in its infancy, and the added benefit (if any) of combining IM with LC-MS/MS has not been studied systematically.…”

Section: Introductionmentioning

confidence: 99%

Analyzing complex mixtures of drug-like molecules: Ion mobility as an adjunct to existing liquid chromatography-(tandem) mass spectrometry methods

Boschmans

Lemière

Sobott

2017

Journal of Chromatography A

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Please cite this article as: Jasper Boschmans, Filip Lemière, Frank Sobott, Analyzing complex mixtures of drug-like molecules: ion mobility as an adjunct to existing liquid chromatography-(tandem) mass spectrometry methods, Journal of Chromatography A http://dx.doi.org/10. 1016/j.chroma.2017.02.015 This is a PDF Þle of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its Þnal form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. AbstractThe use of traveling wave ion mobility mass spectrometry (TWIMS) is evaluated in conjunction with, and as a possible alternative to, conventional LC-MS(/MS) methods for the separation and characterization of drug-like compounds and metabolites. As a model system we use an in vitro incubation mixture of the chemotherapeutic agent melphalan, which results in more than ten closely related hydrolysis products and chain-like oligomers. Ion mobility as a filtering tool results in the separation of ions of interest from interfering ions, based on charge state and shape/size. Different classes of chemical compounds often display different mobilities even if they show the same LC behavior -thereby providing an orthogonal separation dimension. Small molecules with identical or similar m/z that only differ in shape/size (e.g. isomers and isobars, monomers/dimers) can also be distinguished using ion mobility. Similar to retention times and mass-to-charge ratios, drift times are analyte-dependent and can be used as an additional identifier. We find that the compound melphalan shows two different drift times due to the formation of gas-phase charge isomers (protomers). The occurrence of protomers has important implications for ion mobility characterization of such analytes, and also for the interpretation of their fragmentation behavior (CID) in the gas phase.

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Protomers of Benzocaine: Solvent and Permittivity Dependence

Cited by 202 publications

References 33 publications

Studying Gas-Phase Interconversion of Tautomers Using Differential Mobility Spectrometry

Studying Gas-Phase Interconversion of Tautomers Using Differential Mobility Spectrometry

From Compact to String—The Role of Secondary and Tertiary Structure in Charge-Induced Unzipping of Gas-Phase Proteins

Analyzing complex mixtures of drug-like molecules: Ion mobility as an adjunct to existing liquid chromatography-(tandem) mass spectrometry methods

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