Imaging the Redox Network of Metabolic Acids with Matrix Assisted Laser Desorption and Photoinduced Electron Transfer Ionization Mass Spectrometry

Metabolic acids may be present as neutral molecules, dipolar ions, or polyprotic anions in various physiological and pathological processes with different net charges, which challenge charge-dependent mass spectrometric detection. In addition, because protonation or deprotonation is the major ionization route in current organic mass spectrometry, it is also impossible to detect other redox metabolites that do not have active protons. A matrix assisted laser desorption and photoinduced electron transfer ionization mass spectrometric imaging (MALDI^ET-MSI) technique has been developed as a spatial metabolomic tool to investigate the missing part of the redox network. It is based on photo active matrix materials such as 1-amino-2,4-dichloronaphthalene that contain structural units for the absorption of laser irradiation and generate electrons for the ionization of redox active species through electron transfer. MALDI^ET-MSI not only reveals metabolic acids in the tricarboxylic acid (TCA) cycle but also localizes various redox active metabolites that have been underexplored. It provides high spatial resolution that can differentiate the cancer region, adjacent region and normal tissue region. The leveling effects of basic or acidic matrix materials that cause extensive deprotonation or protonation are avoided. The detection of extended metabolome makes it possible to retrieve the connection of glycolytic pathways with lipogenesis, amino acid synthesis as well as various unknown pathways that has been overlooked.