State Key Laboratory for Oncogenes and Related Genes, School of Biomedical Engineering and Institute of Medical Robotics, Shanghai Jiao Tong University, Shanghai, 200030, P. R. China.
Instrumental Analysis Center, Shanghai Jiao Tong University, Shanghai, 200030, P. R. China.
Angew Chem Int Ed Engl. 2021 May 10;60(20):11310-11317. doi: 10.1002/anie.202100734. Epub 2021 Mar 24.
Mass spectrometry (MS) promises small-metabolite profiling as a tool of the future and calls for the comprehensive understanding of key procedures to enhance its capability. Herein, we studied cation adduction and fragmentation of small metabolites by a combination of theoretical and experimental approaches, via nanoparticle-assisted laser desorption/ionization (LDI)-MS and MS/MS. We calculated the energies of adduction conformers and atomic bond orders to establish the rules of cation-metabolite affinity and multiple cation adductions in charge transfer. Further, we demonstrated the reaction paths of adducted ions and mapped the potential energy surfaces to characterize the loss of given groups during fragmentation. Finally, we successfully controlled metabolite fragmentation by selected and multiple adductions to enhance the atomic/fragment coverage as defined for metabolite identification toward profiling. Considering the success of MS in the analysis of large biomolecules, our work may have an impact and guide to advanced analysis of small metabolites.
质谱（MS）有望成为未来的小分子代谢组学分析工具，需要全面了解关键步骤以提高其性能。在此，我们通过纳米颗粒辅助激光解吸/电离（LDI）-MS 和 MS/MS 的组合，结合理论和实验方法，研究了小分子代谢物的阳离子加成和碎裂。我们计算了加合构象的能量和原子键级，以建立阳离子-代谢物亲和性和电荷转移中多阳离子加成的规则。此外，我们还展示了加合离子的反应路径，并绘制了势能面以描述碎裂过程中给定基团的损失。最后，我们通过选择和多重加成成功地控制了代谢物的碎裂，以增强原子/碎片覆盖率，从而实现对代谢物的鉴定和分析。考虑到 MS 在分析大生物分子方面的成功，我们的工作可能会产生影响，并为小分子的高级分析提供指导。
