Non-covalent double bond sensors for gas-phase infrared spectroscopy of unsaturated fatty acids

Abstract

The position and configuration of carbon-carbon double bonds in unsaturated fatty acids is crucial for their biological functions and influences health and disease. However, double bond isomers are not routinely distinguished by classical mass spectrometry workflows. Instead, they require sophisticated analytical approaches usually based on chemical derivatization and/or instrument modification. In this work, a novel strategy to investigate fatty acid double bond isomers (18:1) without prior chemical treatment or modification of the ion source was implemented by non-covalent adduct formation in the gas phase. Fatty acid adducts with sodium, pyridinium, trimethylammonium, dimethylammonium, and ammonium cations were characterized by a combination of cryogenic gas-phase infrared spectroscopy, ion mobility-mass spectrometry, and computational modeling. The results reveal subtle differences between double bond isomers and confirm three-dimensional geometries constrained by non-covalent ion-molecule interactions. Overall, this study on fatty acid adducts in the gas phase explores new avenues for the distinction of lipid double bond isomers and paves the way for further investigations of coordinating cations to increase resolution. Graphical abstract

Cryogenic infrared spectroscopy provides mechanistic insight into the fragmentation of phospholipid silver adducts

“…To gain a fundamental understanding of fragmentation processes in tandem mass spectrometry, however, cryogenic IR spectroscopy is a very powerful technique. A better identification of double bond and sn -isomers might be achieved in the future, e.g., by enhancing diagnostic spectral differences by chemical modification [ 34 ].…”

Review of Recent Advances in Lipid Analysis of Biological Samples via Ambient Ionization Mass Spectrometry

“…Figure 5C shows the experimental setup of the online 1 O 2 derivatization of the C=C bond combined with nano-DESI-MS. Moreover, a combined approach of cryogenic gas-phase infrared spectroscopy, ion mobility-mass spectrometry (IM-MS), and quantum chemical calculations for the investigation of the C=C positional in FAs isomers was implemented by a non-covalent formation without chemical treatments or instruments modifications [61]. In summary, among the above-mentioned derivatization methods (such as the PB reaction, OzID, UVPD, epoxidation by m-CPBA, PAA and HAuCl4, plasma oxidation, electrochemical epoxidation, and 1 O2), the PB reaction is the most classic photochemical strategy used for pinpointing C = C location isomers of unsaturated lipids in both shotgun analysis [16,23] and high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) [7,8,45] workflow.…”

“…Metabolites 2021, 11, x 7 of 19 gas-phase infrared spectroscopy, ion mobility-mass spectrometry (IM-MS), and quantum chemical calculations for the investigation of the C = C positional in FAs isomers was implemented by a non-covalent formation without chemical treatments or instruments modifications[61].…”

Emerging scientists in analytical sciences: Carla Kirschbaum

“…Because gas‐phase infrared spectra of lipids were not reported in the literature at the beginning of my PhD, I could freely choose my projects within this unexplored area. Following the glycolipid project, I investigated other kinds of isomerism in other lipid classes, for example double bond regio‐ and stereoisomers in sphingolipids and fatty acids 3,4 . Towards the end of my PhD studies, I became interested in studying lipid fragmentation mechanisms in tandem mass spectrometry.…”

“…bond regio-and stereoisomers in sphingolipids and fatty acids. 3,4 Towards the end of my PhD studies, I became interested in studying lipid fragmentation mechanisms in tandem mass spectrometry.…”