Solid-State 17O NMR for Studies of Organic and Biological Molecules

Published April 24, 2023

Dimer formation of α-D-glucose molecules in the crystal lattice of D-glucose/NaCl (1:1) co-crystal.

Chemists are rarely able to use oxygen NMR to determine molecular structures, since ¹⁷O is an extremely challenging nucleus to observe. This work provides a mechanism for obtaining a complete set of ¹⁷O NMR parameters for a glucose molecule, paving the way for researchers to consider ¹⁷O NMR as a new spectroscopic tool.

What did scientists discover?

MagLab users have developed a synthetic strategy for introducing ¹⁷O-labels into the D-glucose molecule in a site-specific fashion and then applied state-of-the-art nuclear magnetic resonance (NMR) techniques to obtain a complete set of ¹⁷O NMR parameters. This is the first time that a complete set of ¹⁷O NMR parameters has been recorded for any carbohydrate compound.

Why is this important?

Organic and biological molecules can be thought of as jigsaw puzzles made out of four types of pieces (Hydrogen, Carbon, Nitrogen, and Oxygen). Since ¹⁷O is an extremely challenging nucleus to observe, oxygen is the only key constituent of organic and biological molecules that has remained largely “invisible” to the NMR spectroscopic techniques of chemists. So, essentially chemists are trying to solve these puzzles without the oxygen atoms! Here, researchers are working to make these oxygen atoms “visible” to NMR, providing that “last piece of the puzzle” in biomolecular NMR spectroscopy.

Researchers can now explore whether and how ¹⁷O-labeled glucose can be used as a new tracer for probing the binding of glucose to other biological macromolecules - such as glucose transport proteins - or for monitoring glycolysis of live cancer cells. It may eventually be possible to extend the same methodology to introduce ¹⁷O-labels into more complex carbohydrate molecules such as polysaccharides, or into the ribose/deoxyribose part of RNA/DNA molecules.

Broadly stated, this work adds ¹⁷O NMR to the “NMR tool box” available to chemists for the study of the wide variety of oxygen-bearing materials of interest, including organic and biological molecules.

Who did the research?

Jiahui Shen¹, Victor Terskikh², Jochem Struppe³, Alia Hassan³, Martine Monette³, Ivan Hung⁴, Zhehong Gan⁴, Andreas Brinkmann², Gang Wu¹

¹Queen’s University; ²National Research Council Canada; ³Bruker BioSpin; ⁴National MagLab.

Why did they need the MagLab?

The measurement required the most powerful NMR magnet in the world, the MagLab’s 35.2T Series Connected Hybrid magnet to overcome the intrinsically low NMR sensitivity of the ¹⁷O nuclei. The significantly-boosted sensitivity was critical to the successful detection of ¹⁷O NMR signals from D-glucose. The ultrahigh magnetic field also provides an unprecedented NMR resolving power that is uniquely suited to the study of carbohydrate compounds in which all oxygen-containing functional groups are chemically similar.