Voltage-Controlled Divergent Cascade of Electrochemical Reactions for Characterization of Lipids at Multiple Isomer Levels Using Mass Spectrometry. Academic Article uri icon


  • Cascading divergent reactions in a single system is highly desirable for their intrinsic efficiency and potential to achieve multilevel structural characterization of complex biomolecules. In this work, two electrochemical reactions, interfacial electro-epoxidation and cobalt anodic corrosion, are divergently cascaded in nanoelectrospray (nESI) and can be switched at different voltages. We applied these reactions to lipid identification at multiple isomer levels using mass spectrometry (MS), which remains a great challenge in structural lipidomics. The divergent cascade reactions in situ derivatize lipids to produce epoxidized lipids and cobalt-adducted lipids at different voltages. These lipids are then fragmented upon low-energy collision-induced dissociation (CID), generating diagnostic fragments to indicate CC locations and sn-positions that cannot be achieved by the low-energy CID of native lipids. We have demonstrated that lipid structural isomers show significantly different profiles in the analysis of healthy and cancerous mouse prostate samples using this strategy. The application of divergent cascade reactions in lipid identification allows the four-in-one analysis of lipid headgroups, fatty acyl chains, CC locations, and sn-positions simply by tuning the nESI voltages within a single experiment. This feature as well as its low sample consumption, no need for an extra apparatus, and quantitative analysis capability show its great potential in lipidomics.

published proceedings

  • Anal Chem

altmetric score

  • 2.5

author list (cited authors)

  • Tang, S., Chen, X. i., Ke, Y., Wang, F., & Yan, X.

citation count

  • 8

complete list of authors

  • Tang, Shuli||Chen, Xi||Ke, Yuepeng||Wang, Fen||Yan, Xin

publication date

  • January 2022