Differentiation of Cis/trans-geometrical isomers in long-chain unsaturated fatty acids based on ion mobility and theoretical calculations

In recent years, fatty acids containing conjugated C Cs have attracted extensive research attention due to their biological activities against human diseases. However, their differentiation is challenging. This study developed a comprehensive analytical solution to accurately differentiate cis/trans- fatty acid isomers using ion mobility mass spectrometry (IM-MS) and theoretical calculations. Cis/trans -fatty acids were mobility-differentiated via simple complexation with 1,5,9-triazacyclododecane (9C3N) or 1,4,8,11-tetraazacyclotetradecane (10C4N) and metal ions , obtaining baseline separation with a peak-to-peak resolution of 0.35–0.92. Moreover, the conformation of the complexes was optimized theoretically, revealing different binding modes between the cis / trans- fatty acid-9C3N/10C4N–metal ion systems, yielding in-depth structural data on the complexes and elucidating the principles of mobility separation. Furthermore, the proposed method was assessed in terms of quantification, accuracy, and precision repeatability. Finally, the method was applied to analyze oil samples. Given its simplicity, speed, and lack of chemical derivatization or chromatographic separation, this technique has potential applications in food analysis .