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.