Simultaneous Determination\nof the Position and <i>Cis</i>–<i>Trans</i> Configuration of Lipid\nCC Bonds via Asymmetric Derivatization and Ion Mobility–Mass\nSpectrometry

The position and <i>cis</i>–<i>trans</i> configuration of CC bonds in unsaturated lipids\nsignificantly\naffect their biological activities. Simultaneous identification of\nthe position and <i>cis</i>–<i>trans</i> configuration of CC bonds in unsaturated lipids is important;\nnonetheless, it still remains a challenging task. Herein, a stereoselective\nasymmetric reaction was used to recognize <i>cis</i>–<i>trans</i> isomers of the CC bonds, and the derivatized\nprecursor ions and product ions were subjected to tandem ion mobility–mass\nspectrometry (IM–MS) analysis. The theoretical calculation\nrevealed that the formation of intramolecular hydrogen bonds after\nthe cyclization reaction amplified the structural difference between\ndiastereomers and increased the separation efficiency in IM. Consequently,\na simple, sensitive, and highly selective platform for simultaneous\ndetermination of the position and <i>cis</i>–<i>trans</i> configuration of various CC bonds in unsaturated\nlipids was established. It was then successfully applied to pinpoint\nthe <i>cis</i>–<i>trans</i> geometry conversion\nof the located CC bonds in lipids of the bacterial membrane\nunder environmental stress and track the heterogeneous distribution\nof unsaturated lipids in rats after spinal cord injury. The present\nstudy also offers new insights into the application of IM–MS\ntechnology in resolving molecular structures and demonstrates the\npotential as a platform for a broad range of applications.