Characterizing Nonpolar Sterol Lipids Using a Novel N–H Aziridination Method

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Researchers from Texas A&M University presented a new N–H aziridination method designed to target carbon–carbon double bonds in nonpolar sterol lipids.

A recent study published in the Journal of American Society of Mass Spectrometry introduced a new method for characterizing nonpolar lipids (1). Researchers from Texas A&M University, in Lubbock, Texas, discussed how this novel method, called N–H aziridination, advances lipidomics and analytical chemistry.

Characterizing lipids, especially nonpolar lipids, is important for several key reasons. Lipids, as defined in a study by Journal of Lipid Research, are a large group of organic compounds that include fats, sterols, waxes, monoglycerides, diglycerides, fat-soluble vitamins, and phospholipids (2). Lipids have many critical functions in human organisms. They store energy, and signal and act as structural components as cell membranes (3).

Nonpolar lipids play a crucial role in various biological functions and can exist in multiple isomeric forms (1). Accurately characterizing them has long been a challenge (1). The N–H aziridination method that the researchers proposed in the article was designed to target carbon–carbon double bonds (C=C bonds) in nonpolar sterol lipids (1).

What sets this approach apart is its ability to generate specific fragment ions for determining the position of C=C bonds and fingerprint fragments for characterizing the lipid backbone (1). As a result, the N–H aziridination method could be beneficial in potential applications ranging from disease diagnosis to drug development.

This method offers the advantage of enhancing lipid ionization efficiency and allows for improved sensitivity and accuracy in nonpolar lipid analysis (1). In the study, the researchers demonstrated that aziridination of sterols provides distinct fragmentation pathways for chain and ring C=C bonds, enabling the identification of sterol isomers like desmosterol and 7-dehydrocholesterol (1).


Furthermore, aziridination aids in identifying the sterol backbone by offering unique tandem mass spectra, providing researchers with a comprehensive view of these complex molecules (1).

Another important feature of the N–H aziridination method is its quantitative capacity. The researchers tested this capability in the study and found that the method had a limit of detection (LOD) of 10 nM in a solvent mixture of water and methanol (1). By using mouse prostate cancerous tissues, the researchers proved that the technique can be applied to complex biological samples (1). The scientists concluded that there were differences between the nonpolar lipid profiles of cancerous and healthy samples, which means that the method could be used for diagnostic applications of biological samples (1). Their new method offers key advantages in this field, and it can be used to study biological samples.


(1) Hirtzel, E.; Edwards, M.; Freitas, D.; Liu, Z.; Wang, F.; Yan, X. Aziridination-Assisted Mass Spectrometry of Nonpolar Sterol Lipids with Isomeric Resolution. J. Am. Soc. Mass Spectrom. 2023, 34 (9), 1998–2005. DOI: 10.1021/jasms.3c00161

(2) Fahy, E.; Subramaniam, S.; Murphy, R. C.; et al. Update of the LIPID MAPS comprehensive classification system for lipids. J. Lipid Res. 2009, 50, S9–S14. DOI: 10.1194/jlr.R800095-JLR200

(3) Subramaniam, S.; Fahy, E.; Gupta, S.; et al. Bioinformatics and Systems Biology of the Lipidome. Chem. Rev. 2012, 111 (10), 6452–6490. DOI: 10.1021/cr200295k