Characterisation of sulphoxides by atmospheric pressure ionisation mass spectrometry

Wright, Patricia; Alex, Alexander; Gibson, Drew; Jones, Russell M.; Macrae, P.V.

doi:10.1002/rcm.2015

Cited by 16 publications

(14 citation statements)

References 12 publications

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“…The characterisation of sulphoxides carried out by Wright et al . utilised this approach to help identify the most favourable site of protonation and then to help rationalise the experimentally observed fragmentation and the structures of the product ions 23. Holman et al .…”

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confidence: 99%

Can density functional theory (DFT) be used as an aid to a deeper understanding of tandem mass spectrometric fragmentation pathways?

Alex

Harvey

Parsons

et al. 2009

Rapid Comm Mass Spectrometry

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Prediction of tandem mass spectrometric (MS/MS) fragmentation for non-peptidic molecules based on structure is of immense interest to the mass spectrometrist. If a reliable approach to MS/MS prediction could be achieved its impact within the pharmaceutical industry could be immense. Many publications have stressed that the fragmentation of a molecular ion or protonated molecule is a complex process that depends on many parameters, making prediction difficult. Commercial prediction software relies on a collection of general heuristic rules of fragmentation, which involve cleaving every bond in the structure to produce a list of 'expected' masses which can be compared with the experimental data. These approaches do not take into account the thermodynamic or molecular orbital effects that impact on the molecule at the point of protonation which could influence the potential sites of bond cleavage based on the structural motif. A series of compounds have been studied by examining the experimentally derived high-resolution MS/MS data and comparing it with the in silico modelling of the neutral and protonated structures. The effect that protonation at specific sites can have on the bond lengths has also been determined. We have calculated the thermodynamically most stable protonated species and have observed how that information can help predict the cleavage site for that ion. The data have shown that this use of in silico techniques could be a possible way to predict MS/MS spectra.

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confidence: 99%

Can density functional theory (DFT) be used as an aid to a deeper understanding of tandem mass spectrometric fragmentation pathways?

Alex

Harvey

Parsons

et al. 2009

Rapid Comm Mass Spectrometry

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“…This could correspond to a loss of a methyl unit. Literature confirms that this fractionation pattern strongly indicates an oxygenation of the sulphur 16…”

Section: Resultsmentioning

confidence: 53%

Identification of disinfection by‐products of selected triazines in drinking water by LC‐Q‐ToF‐MS/MS and evaluation of their toxicity

Brix¹,

Bahí²,

Alda³

et al. 2008

J. Mass Spectrom.

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During the development of an on-line solid phase extraction-liquid chromatography-ultraviolet detection (SPE-LC-UV) analytical method for determination of eight selected triazines; ametryn, atrazine, cyanazine, metrybuzine, prometryn, propazin, simazine, and terbutryn, in drinking water, it was observed that the retention times of three of them (ametryn, prometryn, and terbutryn) in Milli-Q water were different from those in chlorinated Milli-Q water, indicating the formation of new products. The cause of this change was found in the oxidation of the molecules as a result of chlorination with sodium hypochlorite. Experiments performed at varying concentrations of triazines and hypochlorite showed that the extent of the reaction depended on their relative concentrations. At the maximum admissible level of 100 ng/l for individual pesticides in drinking water, no apparent transformation was observed in the absence or at low concentrations (0.05 mg/l) of hypochlorite; however, on increasing the concentration of hypochlorite to the level typically present in drinking water (0.9 mg/l) the transformation was complete. The reaction is quite fast; within 1 h the parent compound is completely degraded and after 22 h the concentrations of the by-products are constant. Investigation of the by-products by ultra performance liquid chromatography-quadrupole-time of flight- tandem mass spectrometry (UPLC-Q-ToF-MS/MS) has shown that all three triazines follow a similar transformation pathway, forming four new molecules whose structure have been elucidated. The acute toxicity of the new products was investigated using a standard method based on the bioluminescence inhibition of Vibrio fischeri, and the by-products showed a higher toxicity than that of the parent compounds.

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“…These values are comparable to those used to assign the sulfoxide oxygen as the site of protonation in a previous study. 2 Hence, it can be concluded that the most energetically favourable site of protonation for 4-benzenesulfinyl-3-methylphenylamine is the sulfoxide oxygen. This finding suggests that the 17 m/z unit loss from protonated 4-benzenesulfinyl-3-methylphenylamine is more likely to be a hydroxyl radical than the alternative, a molecule of ammonia.…”

Section: Resultsmentioning

confidence: 99%

“…1 Previous studies have investigated the structural features which lead to specific product ions or losses being observed for different classes of compounds using electrospray ionisation tandem mass spectrometry (ESI-MS/MS). [1][2][3] This approach is of interest for pharmaceutical drug metabolite identification because the fragmentation behaviour may indicate the type of metabolic change that has occurred, e.g.…”

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confidence: 99%

High‐throughput approaches towards the definitive identification of pharmaceutical drug metabolites. 1. Evidence for an ortho effect on the fragmentation of 4‐benzenesulfinyl‐3‐methylphenylamine using electrospray ionisation mass spectrometry

Holman

Wright

Langley

2008

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A 50 m/z unit loss from protonated 4-benzenesulfinyl-3-methylphenylamine has been observed and investigated using electrospray ionisation quadrupole ion trap mass spectrometry (ESI-QIT-MS). It was hypothesised that the specific fragmentation was affected by the presence of an ortho methyl group in relation to the sulfoxide functionality, i.e. an ortho effect influences the preferred dissociation pathway. This was because the des-methyl homologue did not display a 50 m/z unit loss. This fragmentation was shown to be a two-step process with sequential losses of a hydroxyl radical and a thiol radical. Molecular modelling calculations showed that the most favourable site of protonation for 4-benzenesulfinyl-3-methylphenylamine was the sulfoxide oxygen, which would facilitate the loss of a hydroxyl radical. Subsequent deuterium-exchange experiments confirmed that the loss was a hydroxyl radical and afforded definitive assignment of the site of protonation. Furthermore, the involvement of a single exchangeable hydrogen atom in the overall 50 m/z unit loss was demonstrated. Thus, supportive evidence was provided for the involvement of the ortho methyl group in the second stage of the fragmentation, leading to the loss of the thiol radical. Accurate mass measurements, performed using electrospray ionisation Fourier transform ion cyclotron resonance mass spectrometry (ESI-FTICR-MS), verified the elemental formulae of the individual losses. The ion structure following the 50 m/z unit loss was proposed to be a protonated aminofluorene and was supported by comparing the product ion spectrum of commercially available protonated 2-aminofluorene with the MS4 data of protonated 4-benzenesulfinyl-3-methylphenylamine. Fragmentation mechanisms are proposed. The relevance of the loss with regards to pharmaceutical drug metabolite identification is discussed.

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Characterisation of sulphoxides by atmospheric pressure ionisation mass spectrometry

Cited by 16 publications

References 12 publications

Can density functional theory (DFT) be used as an aid to a deeper understanding of tandem mass spectrometric fragmentation pathways?

Can density functional theory (DFT) be used as an aid to a deeper understanding of tandem mass spectrometric fragmentation pathways?

Identification of disinfection by‐products of selected triazines in drinking water by LC‐Q‐ToF‐MS/MS and evaluation of their toxicity

High‐throughput approaches towards the definitive identification of pharmaceutical drug metabolites. 1. Evidence for an ortho effect on the fragmentation of 4‐benzenesulfinyl‐3‐methylphenylamine using electrospray ionisation mass spectrometry

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