Development of an Efficient On-Tissue Epoxidation Reaction Mediated by Urea Hydrogen Peroxide for MALDI MS/MS Imaging of Lipid C═C Location Isomers

Abstract

Unsaturated lipids containing different numbers and locations of C�C bonds are significantly associated with a variety of cellular and metabolic functions. Although matrixassisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) has been used to visualize the spatial distribution patterns of various lipids in biological tissues, in situ identification, discrimination, and visualization of lipid C�C location isomers remain challenging. Herein, an efficient and fast on-tissue chemical derivatization (OTCD) approach was developed to pinpoint the locations of C�C bonds in complex lipids in situ via methyltrioxorhenium (MTO)-catalyzed epoxidation of C�C with a urea hydrogen peroxide (UHP)/hexafluoroisopropanol (HFIP) system. The efficiency of OTCD could reach 100% via one-step spray deposition of the solution mixture of MTO/UHP/HFIP at room temperature. The developed OTCD method provided rich structural information on lipid C�C location isomers, and their accurate spatial distribution patterns were resolved in mouse brain tissues. Tissue-specific distributions and changes of lipid C�C location isomers in the liver sections of obese ob/ob and diabetic db/db mice were further investigated, and their correlation in two animal models was revealed. The simplicity and high efficiency of the OTCD method developed for MALDI tandem MSI of lipid C�C location isomers possess great potential for functional spatial lipidomics.

Mass spectrometry in the age of green analytical chemistry

“…130 It is commonly reported that derivatization singlehandedly makes the detection of certain molecules possible by exponentially improving the sensitivity, accuracy, or detection limit of analysis, indicating the necessity of green derivatization. 131–134 Derivatization can be considered a synthetic process on a smaller scale, 135 and in practice, the experimental operations involved in derivatization typically coincide with the sample preparation process. Therefore, the applicable strategies are similar to those in the said aspects: reduction of the use and toxicity of reagents, reduction of energy consumption, miniaturization, improvement of automation and throughput, etc.…”

Mass spectrometry imaging of Arabidopsis thaliana with in vivo D2O labeling

“…D 2 O labeling is particularly attractive for the isotope tracing of lipids as successfully demonstrated for Arabidopsis in this work and previously for duckweeds. While many isomers are still possible for the lipid species with the same molecular formulae depending on fatty acid chain length, sn-position, and double-bond position, many technical advancements are being made to resolve this issue including MS/MS imaging (Sun et al, 2023), MSI with ion mobility separation (Jiang et al, 2023), and ozone (Claes et al, 2021) or other chemical reactions (Li et al, 2024) to determine the double-bond position.…”

Mass spectrometry imaging for spatially resolved multi-omics molecular mapping

“…For instance, peracetic acid assisted on-tissue epoxidation of unsaturated fatty acids was developed for profiling fatty acid double bond positional isomers in the mouse tumor tissues 98 . Another on-tissue chemical derivatization method developed by Sun et al 99 uses methyltrioxorhenium (MTO)-catalyzed epoxidation of double bonds (within lipids) with a urea hydrogen peroxide (UHP)/hexafluoroisopropanol (HFIP) system. To further improve the MS/MS throughput in chemical derivatization strategies assisted MSI, Guo et al 100 utilized on-tissue Paternò–Büchi (PB) derivatization and a miniature dual-LIT mass spectrometer for high throughput MS/MS imaging of phospholipid isomers.…”