Mass spectrometry-based identification of ortho-, meta- and para-isomers using infrared ion spectroscopy

Outersterp, Rianne E. van; Martens, Jonathan; Berden, Giel; Koppen, Valerie; Cuyckens, Filip

doi:10.1039/d0an01119c

Cited by 14 publications

(18 citation statements)

References 41 publications

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“…The Cs + ion is the dominant fragmentation product formed and is well above the low-mass cut-off of the mass spectrometer (in contrast, Na + and K + are below the low-mass cut-off) and thus can be included in IRMPD yield calculations. The use of IRMPD yield instead of depletion of the precursor intensity can significantly improve the signal-to-noise ratio by accounting for fluctuations in total ion intensity during electrospray. , The Cs + tag likely has some influence on the conformation and IRMPD spectrum; however, Cs + has been shown to have less of an impact in comparison to other adducts such as Na + due to its much larger ionic radius, more diffuse charge, and much weaker binding energy. ,,, Once the lowest-energy conformers are determined, DFT calculations with and without the Cs + ion can provide insights into the overall effect of this weakly bound ion on the gas-phase conformation. ,,,− Finally, as noted above, the absolute intensity of the spectral bands is higher in the Cs + spectrum due to the decreased dissociation energy.…”

Section: Resultsmentioning

confidence: 99%

UV/Vis and IRMPD Spectroscopic Analysis of the Absorption Properties of Methylglyoxal Brown Carbon

Legaard

Thrasher

et al. 2021

ACS Earth Space Chem.

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Brown carbon (BrC) organic molecules absorb solar radiation in the visible range and thus can influence the optical properties of atmospheric aerosol particles and cloud droplets. The absorption properties for different types of BrC can change depending on the chemical environment of the chromophores. Here, the absorption cross sections and the photo-decay rates for BrC molecules formed from methylglyoxal (MG) mixed with ammonium sulfate (MG BrC) are investigated as a function of pH. In solutions acidified to pH ∼2, MG BrC shows an ∼16 nm blueshift in peak absorbance compared to neutral solutions (pH ∼8). To probe the origins of this shift, the gas-phase infrared ion spectra of protonated and neutral imidazole carbonyl (IC), one of the main components of MG BrC, have been measured to provide insights into their structures. Excited-state energy calculations based on these structures suggest that the blueshift occurs for IC in part because protonation of the basic nitrogen in the imidazole ring inhibits conjugation with the carbonyl group attached to the ring. When the photolysis rate of a MG BrC solution that contains IC is extrapolated to atmospheric conditions, the observed blueshift at low pH increases the lifetime of the BrC mixture by ∼42%, with an estimated atmospheric lifetime of ∼82 min. These results highlight the importance of understanding how BrC photolysis rates vary across different environmental conditions.

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Section: Resultsmentioning

confidence: 99%

UV/Vis and IRMPD Spectroscopic Analysis of the Absorption Properties of Methylglyoxal Brown Carbon

Legaard

Thrasher

et al. 2021

ACS Earth Space Chem.

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“…This may imply that the case sample contains a mixture of MW 167 isomers. With this hypothesis in mind and careful inspection of the spectra in Figure , one may estimate which of the isomers are actually present, especially from the 650–900 cm –1 region where ortho-, meta-, and para-isomers have distinct spectral signatures, originating from the out-of-plane CH-bending vibrations of the aromatic ring. , This suggests that 2-FMA (ortho) and 4-FMA (para) are present in the case sample.…”

Section: Resultsmentioning

confidence: 99%

Isomer-Specific Two-Color Double-Resonance IR²MS³ Ion Spectroscopy Using a Single Laser: Application in the Identification of Novel Psychoactive Substances

Geenen

Kranenburg

Asten³

et al. 2021

Anal. Chem.

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The capability of an ion trap mass spectrometer to store ions for an arbitrary amount of time allows the use of a single infrared (IR) laser to perform two-color double resonance IR–IR spectroscopic experiments on mass-to-charge ( m / z ) selected ions. In this single-laser IR 2 MS 3 scheme, one IR laser frequency is used to remove a selected set of isomers from the total trapped ion population and the second IR laser frequency, from the same laser, is used to record the IR spectrum of the remaining precursor ions. This yields isomer-specific vibrational spectra of the m / z -selected ions, which can reveal the structure and identity of the initially co-isolated isomeric species. The use of a single laser greatly reduces the experimental complexity of two-color IR 2 MS 3 and enhances its application in fields employing analytical MS. In this work, we demonstrate the methodology by acquiring single-laser IR 2 MS 3 spectra in a forensic context, identifying two previously unidentified isomeric novel psychoactive substances (NPS) from a sample that was confiscated by the Amsterdam Police.

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“…Vibrational resonances are highly sensitive to details of the molecular structure, such that closely related isomeric molecular ions can often be differentiated on the basis of their IR spectra. Indeed, a range of studies have shown that IRIS can distinguish isomeric small molecules [16][17][18][19][20][21][22][23][24][25][26][27][28] , including several phase-I drug metabolites [29][30][31] . A significant advantage in comparison to techniques based on MS/MS fragmentation patterns is that gas-phase IR spectra can be reliably and efficiently predicted using quantum-chemical calculations based on density functional theory (DFT).…”

Section: Introductionmentioning

confidence: 99%

“…18,32 Previous work has demonstrated IRIS-based differentiation of ortho-, meta-and para-isomers that may result from the hydroxylation of drug compounds containing a phenyl moiety. 29,31 In one of these studies, metabolites were extracted and analyzed from an in vitro drug incubation sample using a combination of LC-MS and IRIS. 29 However, a drug molecule often undergoes several phase I (oxidation, hydrolysis or reduction) and phase II (conjugation) biotransformation reactions that occur sequentially.…”

Section: Introductionmentioning

confidence: 99%

Identification of drug metabolites with infrared ion spectroscopy – application to midazolam in vitro metabolism

Outersterp

Martens

Berden

et al. 2022

Preprint

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The identification of biotransformation products of drug compounds is a crucial step in drug development. Over the last decades, liquid chromatography-mass spectrometry (LC-MS) has become the method of choice for metabolite profiling because of its high sensitivity and selectivity. However, determining the full molecular structure of the detected metabolites, including the exact biotransformation site, remains challenging on the basis of MS alone. Here we explore infrared ion spectroscopy (IRIS) as a novel MS-based method for the elucidation of metabolic pathways in drug metabolism research. Using the drug midazolam as an example, we identify several biotransformation products directly from an in vitro drug incubation sample. We show that IR spectra of the aglycone MS/MS fragment ions of glucuronide metabolites establish a direct link between detected phase I and phase II metabolites. Moreover, using quantum-chemically computed IR spectra of candidate structures, we are able to assign the exact sites of biotransformation in absence of reference standards. Additionally, we demonstrate the utility of IRIS for structural elucidation by identifying several ring-opened midazolam derivatives formed in an acidic environment.

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Mass spectrometry-based identification of ortho-, meta- and para-isomers using infrared ion spectroscopy

Abstract: Distinguishing positional isomers presents a significant challenge for mass spectrometric analyses, for instance in drug metabolism research. We show that IR ion spectroscopy readily identifies ortho-, meta- and para-isomers.

Cited by 14 publications

References 41 publications

UV/Vis and IRMPD Spectroscopic Analysis of the Absorption Properties of Methylglyoxal Brown Carbon

UV/Vis and IRMPD Spectroscopic Analysis of the Absorption Properties of Methylglyoxal Brown Carbon

Isomer-Specific Two-Color Double-Resonance IR²MS³ Ion Spectroscopy Using a Single Laser: Application in the Identification of Novel Psychoactive Substances

Identification of drug metabolites with infrared ion spectroscopy – application to midazolam in vitro metabolism

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Mass spectrometry-based identification of ortho-, meta- and para-isomers using infrared ion spectroscopy

Abstract: Distinguishing positional isomers presents a significant challenge for mass spectrometric analyses, for instance in drug metabolism research. We show that IR ion spectroscopy readily identifies ortho-, meta- and para-isomers.

Cited by 14 publications

References 41 publications

UV/Vis and IRMPD Spectroscopic Analysis of the Absorption Properties of Methylglyoxal Brown Carbon

UV/Vis and IRMPD Spectroscopic Analysis of the Absorption Properties of Methylglyoxal Brown Carbon

Isomer-Specific Two-Color Double-Resonance IR2MS3 Ion Spectroscopy Using a Single Laser: Application in the Identification of Novel Psychoactive Substances

Identification of drug metabolites with infrared ion spectroscopy – application to midazolam in vitro metabolism

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Product

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Isomer-Specific Two-Color Double-Resonance IR²MS³ Ion Spectroscopy Using a Single Laser: Application in the Identification of Novel Psychoactive Substances