Mechanochemistry enables ¹⁷O labeling

Oxygen-17 NMR spectroscopy is one tool that chemists can use to study the structure and reactivity of various organic and inorganic compounds. But ¹⁷O’s low natural abundance—merely 0.04%—requires enriching samples with the isotope, a process that is often costly and time-consuming.

One solution to the challenge of ¹⁷O labeling may be mechanical: Combine a reagent with a stoichiometric amount of ¹⁷O-enriched water and grind the mixture in a ball mill, suggests a team led by Danielle Laurencin of the Institut Charles Gerhardt Montpellier (Angew. Chem. Int. Ed. Engl. 2017, DOI: 10.1002/anie.201702251).

Grinding reagents in a ball mill to induce reactions is a form of mechanochemistry that has gained popularity in recent years as a relatively quick and convenient way to make some organic and inorganic compounds. As the balls collide in the mill, effects such as shear stress and increased temperature may help stimulate chemistry at the interfaces between particles.

Laurencin and colleagues produced ¹⁷O-enriched metal oxides by combining a metal hydroxide with less than two equivalents of ¹⁷O-enriched water, grinding the reagents for 30 minutes, then heating the material to convert it to the metal oxide. Enriching 60 mg of Mg(OH)₂ or Ca(OH)₂ to ¹⁷O levels suitable for solid-state NMR analyses cost the team about $10.

For ¹⁷O NMR of organic compounds, the researchers focused on carboxylic acids, which frequently turn up in biomolecules and metal ligands, such as those in metal-organic frameworks. The researchers first ground the organic compounds with 1,1’-carbonyl-diimidazole to activate the carboxylic groups and then milled the material with ¹⁷O-enriched water. The whole procedure took less than two hours.