Volume-Corrected Free Energy as a New Criterion for Structural Elucidation in Chemical-Tagging-Based Metabolomics

Abstract

Chemical tagging via possible derivatization reagents alters metabolites’ retention times, leading to different retention behavior during liquid chromatography–mass spectrometry (LC–MS) analysis. Incorporation of the retention time dimension can dramatically reduce false-positive structural elucidation in chemical-tagging-based metabolomics. However, few studies predict the retention times of chemically labeled metabolites, especially requiring a simple, easy-to-access, accurate, and universal predictor or descriptor. This pilot study demonstrates the application of volume-corrected free energy (VFE) calculation and region mapping as a new criterion to describe the retention time for structure elucidation in chemical-tagging-based metabolomics. The universality of VFE calculation is first evaluated with four different types of submetabolomes including hydroxyl-group-, carbonyl-group-, carboxylic-group-, and amino-group-containing compounds and oxylipins with similar chemical structures and complex isomers on reverse-phase LC. Results indicate a good correlation (r > 0.85) between VFE values and their corresponding retention times using different technicians, instruments, and chromatographic columns, describing retention behavior in reverse-phase LC. Finally, the VFE region mapping is described for identifying 1-pentadecanol from aged camellia seed oil using three proposed steps, including public database searching, VFE region mapping for its 12 isomers, and chemical standard matching. The possibility of VFE calculation of nonderivatized compounds in retention time prediction is also investigated, demonstrating its effectiveness on retention times with different influence factors.