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Improving the accuracy of 1 H-19 F internuclear distance measurement using 2D 1 H-19 F HOESY.

Lydia DewisRon CrouchDave RussellCraig P Butts
Published in: Magnetic resonance in chemistry : MRC (2019)
With the rise in fluorinated pharmaceuticals, it is becoming increasingly important to develop new 19 F NMR-based methods to assist in their analysis. Crucially, obtaining information regarding the conformational dynamics of a molecule in solution can aid the design of strongly binding therapeutics. Herein, we report the development of a 2D 1 H-19 F Heteronuclear Overhauser Spectroscopy (HOESY) experiment to measure 1 H-19 F internuclear distances, with accuracies of ~5% when compared with 1 H-19 F internuclear distances calculated by quantum chemical methods. We demonstrate that correcting for cross-relaxation of 1 H, using the diagonal peaks from the 2D 1 H-1 H Nuclear Overhauser Enhancement Spectroscopy (NOESY), is critical in obtaining accurate values for 1 H-19 F internuclear distances. Finally, we show that by using the proposed method to measure 1 H-19 F internuclear distances, we are able to determine the relative stereochemistry of two fluorinated pharmaceuticals.
Keyphrases
  • single molecule
  • high resolution
  • solid state
  • molecular dynamics
  • magnetic resonance
  • small molecule
  • mass spectrometry
  • binding protein