Azidophenylalanine poses explosion risk

The unnatural amino acid 4-azido-l-phenylalanine (shown, left) carries an explosion risk, a new study shows (J. Org. Chem. 2018, DOI: 10.1021/acs.joc.8b00270). The azide group isn’t found in biology, which makes it handy for attaching probes to biomolecules. The amino acid is expensive, however, so postdoctoral researcher Mark B. Richardson, professor Gregory A. Weiss, and colleagues at the University of California, Irvine, developed a cost-effective synthesis. “We found this explosion risk entirely by accident,” Richardson says. Organic chemists are wary of azides, so the team used differential scanning calorimetry to watch the decomposition profile of all the intermediates in the copper-catalyzed reaction they used to build the molecule. The intermediates, some of which they worried would be problematic, turned out to be safe. But azidophenylalanine, included in the study for completeness’s sake, behaved like an explosive compound. To minimize risks, labs should avoid storing crystalline samples of azidophenylalanine for extended periods, Richardson says. Protecting the amine removes the explosion risk and is a good prestorage strategy. Biochemistry labs should consider keeping all stocks of azidophenylalanine in dilute aqueous solution, he adds. Sometimes people become complacent about risky functional groups, he says. “The fact that we didn’t see this coming speaks volumes.”