A novel on-tissue cycloaddition reagent for mass spectrometry imaging of lipid C=C position isomers in biological tissues

Application of matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to investigate the spatiotemporal alterations of lipids in biological tissues has brought many significant results. However, the presence of structural isomers varying in C = C double bond (DB) locations makes isomer-resolved MSI an urgent need. Herein, we introduce a new type of light-driven on-tissue [2 + 2] cycloaddition reaction coupled with MALDI-MS/MS imaging to identify lipid DB position isomers and their spatial signatures in biological tissues. 3-Benzoylpyridine was introduced as a novel derivatization reagent, and it exhibited great reactivity toward lipid C = C bond to form oxetanes under both ultraviolet light and visible light irradiation. With this approach, DB position isomers of lipids were imaged with highly differential levels in distinct regions of rat brain, providing an accurate and spatially resolved approach to study tissue lipidomics. (C) 2021 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.

Automated summary

The application of matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to investigate the changes of lipids in biological tissues has yielded significant results. However, the presence of structural isomers with varying C=C double bond (DB) locations calls for the development of isomer-resolved MSI. In this study, a new light-driven on-tissue [2 + 2] cycloaddition reaction coupled with MALDI-MS/MS imaging was introduced to identify lipid DB position isomers and their spatial signatures in biological tissues.