Multi-wavelength visible-light induced [2+2] cycloaddition for identification of lipid isomers in biological samples

Ultraviolet (UV) light-catalyzed Paterno-Buchi (PB) reaction has been developed as an efficient lipid C=C double bond (DB) derivatization strategy, which can accurately assign the position of C=C bond in unsaturated lipids when coupled with tandem mass spectrometry (MS/MS). Inspired by this, here we proposed a novel visible-light induced [2+2] cycloaddition reaction combined with ESI-MS/MS and MALDI-MS/MS to identify lipid C=C position isomers. Benz[g]isoquinoline-5,10-dione (BIQD) and 6,9-difluorobenzo[g]isoquinoline-5,10-dione (DF-BIQD) were developed as a new type of [2+2] cycloaddition reagent, which can not only react with C=C bond under 254 nm UV light irradiation, but also quickly combine with lipid C=C bond under the irradiation of 405 nm visible-light and > 400 nm compact fluorescent lamp visible-light. High cycloaddition reaction conversion efficiency can be achieved by irradiating under compact fluorescent lamp light for 2 min. Moreover, we discovered that 437 nm, 489 nm, 545 nm, 581 nm, and 613 nm monochromatic light appearing in compact fluorescent lamp can individually induce the [2 + 2] cycloaddition reaction between DF-BIQD and unsaturated lipids. Using this method, we found that the expressions of lipid DB-positional isomers in rat heart, brain, lung, spleen, thymus, kidney, liver and plasma vary greatly. The relative content of FA-18:1 (Delta 9) in rat heart is only 1.49 times that of FA-18:1 (Delta 11), while the relative content of FA-18:1 (Delta 9) in rat plasma is 5.20 times that of FA-18:1 (Delta 11). The above results offer new insight into the development of photocatalytic reagent for visible-light induced [2+2] cycloaddition and structural lipidomic studies. (C) 2021 Elsevier B.V. All rights reserved.

Automated summary

A novel visible-light induced [2+2] cycloaddition reaction combined with mass spectrometry techniques was proposed to identify lipid C=C position isomers. The new cycloaddition reagents achieved high conversion efficiency under compact fluorescent lamp light, offering new insights into photocatalytic reagent development for visible-light induced cycloaddition and structural lipidomic studies.