Reactive Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging Using an Intrinsically Photoreactive Paternò-Büchi Matrix for Double-Bond Localization in Isomeric Phospholipids.

The location and identity of phospholipids (PLs) within tissues can serve as diagnostic markers for tissue types or diseases. Whereas mass spectrometry imaging (MSI) has emerged as a powerful bioanalytical tool to visualize PL distributions, inferring PL identities from MSI experiments is challenging. Especially, C═C double-bond (DB) positions are not identifiable in most MSI experiments. Herein, we introduce benzophenone (BPh) as a novel reactive matrix for matrix-assisted laser desorption/ionization (MALDI). BPh promotes desorption/ionization and simultaneously serves as derivatization reagent that allows functionalization of unsaturated PLs during the MALDI process via a laser-light driven Paternò-Büchi (PB) reaction without the need for additional equipment. Using BPh, PB product ions of numerous PL classes are readily generated to pinpoint the location of DBs. High lateral resolution MSI results of DB-position isomers are presented, highlighting the capabilities of BPh as a PB-reactive MALDI matrix to potentially unveil the impact of DB-position isomers in PL metabolism.