Laser-induced photochemical click reaction enabling on-line tagging and detection of phosphatidylethanolamine by MALDI-mass spectrometry

Lipids are structural components of biomembrane and also have multiple cellular functions. Lipids are difficult to be studied due to their great diversity. Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) has played an important role in lipid analysis. However, the detection of specific lipids still suffers from challenges such as low selectivity and signal interference from other lipids, especially in complex biological samples. In this study, we have synthesized a series of N-alkyl-9-aminoacridines (N-alkyl-9AAs) with different alkyl chain lengths as the matrices for MALDI-MS analysis of phospholipids and created a unique strategy to distinguish phosphatidylethanolamine (PE) from other membrane phospholipids. A laser-induced ultrafast photochemical click reaction between N-alkyl-9AA and the amino group enabled to selectively tag PE species in source with an apparent yield up to 97%. Meanwhile the interference from phosphatidylcholine, most frequently encountered in MS analysis, was avoided. Among the N-alkyl-9AAs, C6-9AA exhibited the best performances and offered higher detection sensitivity for PEs in comparison to 9AA. This approach was successfully applied to the identification of PEs in Gram-positive and Gram-negative bacteria. This work not only provides a novel matrix for selective analysis of PE but also demonstrates a new way for fast screening of target biomolecules based on photochemical click reaction, avoiding tedious procedures for derivatization. In addition, it makes a valuable contribution to the understanding on the mechanism of MALDI.