Enzymes can make significantly more diazos than before

Emory University researchers led by Kyle Biegasiewicz have repurposed enzymes to produce diazo compounds from hydrazones under milder, greener conditions than traditional chemical methods (J. Am. Chem. Soc. 2026, DOI: 10.1021/jacs.5c17554). “I think it's fascinating for us to learn about the things that enzymes can do” beyond their natural functions, Biegasiewicz says. Diazo compounds are extremely versatile precursors for many carbene-mediated insertion reactions. But the reactions that form diazos tend to be inefficient or reliant on toxic reagents. Biegasiewicz thought this problem might be solvable with the help of the vanadium-dependent haloperoxidase (VHPO) enzymes his group works with. Naturally found in marine algae, VHPOs’ usual function is to attach halogen atoms to molecules. But researchers have found that they can extend that reactivity to forge other types of bonds through a “halide recycling” strategy. In these reactions, the enzyme attaches a halogen to a molecule, and the halogen is later eliminated and returned to the enzyme’s catalytic cycle. All that’s needed is a catalytic amount of a halide salt and hydrogen peroxide as an oxidant.The enzymatic reaction works as part of a two-step, one-pot sequence starting from a carbonyl compound. The first step involves reacting the carbonyl with hydrazine to make a hydrazone. Next, the enzyme converts the hydrazone to a diazo. Both steps take place in a mixture of water and an organic solvent, and the intermediate doesn’t need to be isolated between steps, which makes the process greener and more convenient. The Emory team also found that the