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Fragmentation of Polyfunctional Compounds Recorded Using Automated High-Throughput Desorption Electrospray Ionization
MyPhuong T Le1, Nicolás M Morato1, Andreas Kaerner2
1Department of Chemistry and Bindley Bioscience Center, Purdue University, West Lafayette, Indiana 47907, United States.
Journal of the American Society for Mass Spectrometry
|July 19, 2021
Summary
Experts accurately predicted fragmentation patterns in a pharmaceutical library using tandem mass spectrometry. Substituent effects, particularly aromatic stabilization, influenced fragmentation, guiding future machine learning applications in drug discovery.
Area of Science:
- Analytical Chemistry
- Mass Spectrometry
- Computational Chemistry
Background:
- High-throughput analysis is crucial for pharmaceutical compound libraries.
- Tandem mass spectrometry (MS/MS) provides structural information.
- Predicting MS/MS fragmentation aids structure elucidation.
Purpose of the Study:
- To build a large MS/MS spectral library for pharmaceutical compounds.
- To evaluate expert prediction of fragmentation for specific functional groups.
- To investigate substituent effects on fragmentation pathways.
Main Methods:
- Desorption electrospray ionization (DESI) coupled with automated high-throughput systems.
- Acquisition of tandem mass spectra (MS/MS) in positive mode.
- Expert-driven prediction and comparison of fragmentation patterns for amide, piperazine, and sulfonamide groups.
Main Results:
- A quality-controlled MS/MS library of 16,662 spectra was generated.
- Expert fragmentation predictions showed good to excellent accuracy.
- Aromatic substitution stabilized product ions, influencing fragmentation; homolytic cleavages were observed.
Conclusions:
- Expert MS/MS fragmentation prediction is reliable for key functional groups.
- Substituent effects, especially aromatic stabilization, are critical in fragmentation.
- Findings support the development of machine learning for MS/MS spectrum-structure correlations.
Keywords:
ambient ionizationfragmentationion chemistryspectral interpretationtandem mass spectrometryMore Related Videos
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