Gas-Phase Infrared Spectroscopy in Superfluid Helium Droplets Localizes Sites of Unsaturation in Lipids


C. Kirschbaum, K. Greis, R. Young, E. M. Saied, G. Meijer, G. von Helden, B. L. J. Poad, S. J. Blanksby, C. Arenz, K. Pagel

Fritz-Haber-Institut der Max-Planck-Gesellschaft, Abteilung Molekülphysik, Faradayweg 4-6, 14195 Berlin


Freie Universität Berlin, Institut für Chemie und Biochemie, Arnimallee 22, 14195 Berlin

Lipids are essential biomolecules occurring as edible oils, scaffolds of cell membranes, and hormones. Their structural variety is as vast as their manifold functions, and it is a well-accepted fact that minute structural alterations can crucially influence the biological functionality of a lipid. Lipid analysis must therefore cover all levels of complexity down to the structural details and distinguish between isomers. One very important feature in the structure of unsaturated lipids is the position of C=C double bonds, which influences health and disease. However, mass spectrometry alone cannot distinguish between double bond isomers. Gas-phase infrared (IR) spectroscopy, on the other hand, is a structure-sensitive technique that can reveal subtle structural differences between ions of identical mass. To increase the spectral resolution, analyte ions can be embedded in superfluid helium droplets that act as cryostats preventing ion heating. As C=C vibrations are neither intense nor diagnostic for the position of double bonds, the concept of double bond sensors was developed. Inspired by sphingolipids, which carry a primary amine as an intrinsic probe, covalent and non-covalent double bond sensors were tested for their ability to localize sites of unsaturation in fatty acids.1,2 The performance of the most promising derivatization strategy was showcased for lipid extracts from different cancer cell lines expressing varying levels of fatty acids with unusual double bond positions.

(1)        Kirschbaum, C.; Saied, E. M.; Greis, K.; Mucha, E.; Gewinner, S.; Schöllkopf, W.; Meijer, G.; von Helden, G.; Poad, B. L. J.; Blanksby, S. al. Resolving Sphingolipid Isomers Using Cryogenic Infrared Spectroscopy. Angew. Chem. Int. Ed. 2020, 59, 13638-13642.

(2)        Kirschbaum, C.; Greis, K.; Lettow, M.; Gewinner, S.; Schöllkopf, W.; Meijer, G.; von Helden, G.; Pagel, K. Non-Covalent Double Bond Sensors for Gas-Phase Infrared Spectroscopy of Unsaturated Fatty Acids. Anal. Bioanal. Chem. 2021, 413, 3643-3653.