NSF grant will accelerate SLU researcher's work in sustainable metals

Neely

ST. LOUIS – A $500,000 grant from the National Science Foundation will accelerate research on using sustainable metals, specifically iron, to access valuable molecules.

The three-year grant, "Iron-Catalyzed Three-Component Coupling Methods via Iron Azametallacyclobutene Complexes," was awarded to Jamie Neely, Ph.D., assistant professor of chemistry at Saint Louis University.

Neely is researching new approaches to preparing products valuable to medicine, agriculture, and chemical synthesis through iron-catalyzed three-component coupling chemistry. Specifically, she is seeking to use iron, to make chemical reactions in the creation of pharmaceuticals more sustainable.

"Iron is the most abundant transition metal on Earth," Neely said. "It is cheap and non-toxic and so is an excellent choice when making pharmaceutical drugs and other important products."

Synthetic drug targets that could benefit from this chemistry include Nilotinib, which is used to treat chronic myelogenous leukemia, and Abemaciclib, which acts as a CDK inhibitor in treating metastatic breast cancers.

"We are on the road," Neely said of using sustainable metals in pharmaceutical synthesis. "We aren't there yet, but the car has left the driveway."

These iron complexes can interact with coupling partners in a controlled fashion, making them ideal catalysts for the targeted methods. Neely said the project will showcase how the distinct behavior of Earth-abundant first-row transition metals can be seen as an opportunity, rather than a liability.

This research aims to develop iron-catalyzed three-component coupling reactions of nitrene precursors, alkynes, and nitrile or isonitrile substrates to synthesize value-added, nitrogen-containing compounds. Reactions of nitrile coupling partners will provide a route to imidazoles, a pervasive structural motif in biologically active compounds, with further application to the preparation of diversely substituted N-heterocyclic carbenes.

Iron-catalyzed coupling using isonitrile substrates will access imidoyl ketenimine products that have broad utility as synthetic intermediates.

"We take advantage of iron imide complexes that deliver nitrogen groups and allow access to structures that are common in pharmaceutical drugs," Neely said.

The metals currently used in the synthesis of these compounds come from scarce sources and can be toxic to humans.

"We’re spending all this time and energy getting residual metals out of the drug products at the end of the reactions," she said. "If we can make these products with iron, it would minimize toxicity risks and save a lot of effort and money."

Neely said the grant funding would accelerate her work, allowing research in her lab to proceed more efficiently.

"This grant gives us access to things we didn't have before, like materials that we were previously synthesizing ourselves in the lab," she said. "Now we can really focus our efforts on developing this exciting chemistry."