Conversion of dinitrogen to ammonia is a process that’s both essential to life on Earth and industrially important in fertilizer production. Researchers have long studied the enzymes that living things use to promote the reaction, but details of their catalytic mechanisms have remained elusive.

Now, Caltech scientists have created an iron complex that catalyzes this conversion in a manner that may help reveal the way nitrogenases do it. The iron catalyst and earlier molybdenum versions could also help lead to improved catalysts for reducing N₂ to NH₃ industrially.

Bacteria make nitrogenases and use them to convert N₂ in air to NH₃, a process called nitrogen fixation. The process is a primary source of nitrogen in proteins, nucleic acids, and other biomolecules. The Haber-Bosch process, which was developed in the early-20th century and uses a solid iron catalyst for adding H₂ to N₂ at high temperatures and pressures to form NH₃ for fertilizer production, is now also a primary source of fixed nitrogen.

Most nitrogenases have an active-site cofactor—a molybdenum-iron cluster—but researchers don’t yet know whether it’s Mo or Fe that coordinates and reduces N₂. In 2003, Richard R. Schrock’s group at MIT developed the first Mo complex that catalyzes N₂ to NH₃ conversion under mild conditions.Yoshiaki Nishibayashi of the University of Tokyo and coworkers reported another such Mo complex two years ago. Both Mo complexes are inefficient catalysts and break down quickly, but they work. That could not be said for any Fe-based complex, favoring the idea that nitrogenase’s Mo is the active metal.

John S. Anderson, Jonathan Rittle, and Jonas C. Peters at Caltech have now come up with the first Fe-based complex that directly catalyzes nitrogen fixation to NH₃ under mild conditions (Nature 2013, DOI: 10.1038/nature12435).

The tris(phosphine)borane-supported Fe-N₂ -complex’s catalytic activity is slightly lower than the Mo catalysts’, and it likewise breaks down quickly. But its supporting ligand “can be varied systematically to improve the catalyst, so there are good prospects for future improvement,” notes Patrick L. Holland of Yale University, who specializes in Fe-based cleaving reactions.

The Fe complex tips the balance of evidence back toward the idea that nitrogenase catalysis may be Fe-based. The study “provides favorable information for Fe claimants, but further study is necessary,” Nishibayashi says. One such claimant, Brian M. Hoffman of Northwestern University, says, “You can no longer use the argument that Mo must be it because it’s the only one shown to do the job.”

Peters and coworkers propose that a flexible Fe-boron interaction in their complex may play a key catalytic role and that a carbon-Fe interaction in nitrogenase may work similarly. “Through analogies like this, synthetic compounds can help chemists to gain insight into the mechanisms of enzymes,” Holland says. Nishibayashi also believes the result “provides useful and significant information to elucidate the reaction mechanism of the MoFe cofactor in nitrogenase.” But Schrock says, “It’s a stretch to say it tells us much, if anything, about the mechanism of reduction by various nitrogenases.”

The Fe-based and Mo-based complexes are possible first steps toward developing nitrogen fixation routes that are more economical than the energy-intensive Haber-Bosch process. “The work shows that chemistry just has a much wider range of elements and structures to choose from than nature had during evolution and that mechanistically there may be quite a few possibilities for efficient N₂-fixing complexes,” says bioinorganic chemist Oliver Einsle of the University of Freiburg, in Germany.