Infrared Multiphoton Dissociation Spectroscopy Study of Protonated <i>p</i>-Aminobenzoic Acid: Does Electrospray Ionization Afford the Amino- or Carboxy-Protonated Ion?

Schmidt, Jacob C.; Meyer, Matthew M.; Spector, Ivan C.; Kass, Steven R.

doi:10.1021/jp203829z

Cited by 88 publications

(203 citation statements)

References 33 publications

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“…Interestingly, although the N-protonated form of 4-ABA•H + is the most stable tautomer in protic solution [63], the O-protonated structure is most stable when isolated in the gas-phase. Here, we calculate that O-protonated 4-ABA•H + is 5.6 kcal•mol -1 lower in energy than the N-protonated tautomer, which is in excellent agreement with earlier reported ranges of 4.1-9.5 kcal•mol -1 [54,55]. Interestingly, we find that adding a CH 3 OH molecule stabilizes the O-protonated structure relative to the N-protonated form by a further 3.3 kcal•mol -1 .…”

Section: Resultssupporting

confidence: 92%

“…Earlier confirmation of these two tautomers was achieved by infrared multiple photon dissociation (IRMPD) spectroscopy [55], lowpressure HDX [54], and MS/MS [54,55]. [25,54,55]. It is interesting to note the observed shift in peak CV (particularly obvious for the CV = −1.5 V peak) as a function of water concentration.…”

Section: Resultsmentioning

confidence: 89%

“…These tautomers were preferentially produced via electrospray ionization (ESI) by judicious selection of the ESI solvents [25,54,55]. Earlier confirmation of these two tautomers was achieved by infrared multiple photon dissociation (IRMPD) spectroscopy [55], lowpressure HDX [54], and MS/MS [54,55]. [25,54,55].…”

Section: Resultsmentioning

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: Resultssupporting

confidence: 92%

Section: Resultsmentioning

confidence: 89%

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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

View full text Add to dashboard Cite

show abstract

“…Based on IM and MS/MS data, they conclude that these ions only differ in the site of protonation, and are thus referred to as "protomers". Other studies have reported on the observation of protomers for different analytes using both MS as well as other techniques such as gas-phase infrared photodissociation (IRPD) spectroscopy [56][57][58]. We also explain the observation here of two drift times for melphalan by the presence of charge isomers (protomers) in the gas phase [26].…”

Section: Observation Of Multiple Drift Times For Melphalansupporting

confidence: 58%

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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“…has been raised by Kass et al [19][20][21][22][23][24][25][26][27][28][29]. Generally, we know that protonation occurs predominantly on the most basic site of the molecule to generate the thermodynamically favored protonated ions in ESI.…”

Section: Introductionmentioning

confidence: 99%

The Protonation Site of para-Dimethylaminobenzoic Acid Using Atmospheric Pressure Ionization Methods

Chai

Weng

Shen

et al. 2015

J. Am. Soc. Mass Spectrom.

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Abstract. The protonation site of para-dimethylaminobenzoic acid (p-DMABA) was investigated using atmospheric pressure ionization methods (ESI and APCI) coupled with collision-induced dissociation (CID), nuclear magnetic resonance (NMR), and computational chemistry. Theoretical calculations and NMR experiments indicate that the dimethyl amino group is the preferred site of protonation both in the gas phase and aqueous solution. Protonation of p-DMABA occurs at the nitrogen atom by ESI independent of the solvents and other operation conditions under typical thermodynamic control. However, APCI produces a mixture of the nitrogen-and carbonyl oxygenprotonated p-DMABA when aprotic organic solvents (acetonitrile, acetone, and tetrahydrofuran) are used, exhibiting evident kinetic characteristics of protonation. But using protic organic solvents (methanol, ethanol, and isopropanol) in APCI still leads to the formation of thermodynamically stable N-protonated p-DMABA. These structural assignments were based on the different CID behavior of the N-and O-protonated p-DMABA. The losses of methyl radical and water are the diagnostic fragmentations of the N-and O-protonated p-DMABA, respectively. In addition, the N-protonated p-DMABA is more stable than the O-protonated p-DMABA in CID revealed by energy resolved experiments and theoretical calculations.

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Infrared Multiphoton Dissociation Spectroscopy Study of Protonated p-Aminobenzoic Acid: Does Electrospray Ionization Afford the Amino- or Carboxy-Protonated Ion?

Cited by 88 publications

References 33 publications

Studying Gas-Phase Interconversion of Tautomers Using Differential Mobility Spectrometry

Studying Gas-Phase Interconversion of Tautomers Using Differential Mobility Spectrometry

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

The Protonation Site of para-Dimethylaminobenzoic Acid Using Atmospheric Pressure Ionization Methods

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