EDTA as a chelating agent in quantitative 1H-NMR of biologically important ions

Biochem Cell Biol. 2021 Aug;99(4):465-475. doi: 10.1139/bcb-2020-0543. Epub 2021 Jan 15.


Biologically important ions such as Ca, K, Mg, Fe, and Zn play major roles in numerous biological processes, and their homeostatic balance is necessary for the maintenance of cellular activities. Sudden and severe loss in homeostasis of just one biologically important ion can cause a cascade of negative effects. The ability to quickly, accurately, and reliably quantify biologically important ions in samples of human bio-fluids is something that has been sorely lacking within the field of metabolomics. 1H-NMR spectra. The foundation of our investigation was the a-priori knowledge that free ethylenediaminetetraacetic acid (EDTA) produces two clear single peaks on 1H-NMR spectra, and that EDTA chelated to different ions produces unique 1H-NMR spectral patterns due to 3D conformational changes in the chemical structure of chelated-EDTA and varying degrees of electronegativity. The aim of this study was to develop and test a 1H-NMR-based method, with application specifically to the field of metabolomics, to quantify biologically important ions within the physiological pH range of 6.50-7.50 using EDTA as a chelating agent. Our method produced linear, accurate, precise, and repeatable results for Ca, Mg, and Zn; however, K and Fe did not chelate with EDTA.

Keywords: acide éthylènediaminetétraacétique (EDTA); biological ions; chelation; chélation; ethylenediamine tetraacetic acid (EDTA); ions biologiques; metabolomics methodology; méthodologie en métabolomique; proton nuclear magnetic resonance (1H-NMR) spectroscopy; spectroscopie de résonance magnétique nucléaire du proton (RMN-1H).

MeSH terms

  • Chelating Agents / chemistry*
  • Chelating Agents / metabolism
  • Edetic Acid / chemistry*
  • Edetic Acid / metabolism
  • Humans
  • Metabolomics / methods*
  • Metals / chemistry*
  • Metals / metabolism
  • Proton Magnetic Resonance Spectroscopy / methods*


  • Chelating Agents
  • Metals
  • Edetic Acid