Native mass spectrometry-based metabolomics identifies metal-binding compounds

Nat Chem. 2022 Jan;14(1):100-109. doi: 10.1038/s41557-021-00803-1. Epub 2021 Nov 18.


Although metals are essential for the molecular machineries of life, systematic methods for discovering metal-small molecule complexes from biological samples are limited. Here, we describe a two-step native electrospray ionization-mass spectrometry method, in which post-column pH adjustment and metal infusion are combined with ion identity molecular networking, a rule-based data analysis workflow. This method enabled the identification of metal-binding compounds in complex samples based on defined mass (m/z) offsets of ion species with the same chromatographic profiles. As this native electrospray metabolomics approach is suited to the use of any liquid chromatography-mass spectrometry system to explore the binding of any metal, this method has the potential to become an essential strategy for elucidating metal-binding molecules in biology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Chromatography, Liquid / methods
  • Mass Spectrometry / methods*
  • Metabolomics / methods*
  • Metals / metabolism*


  • Metals