NIH grant will help streamline chemical synthesis

Award to Julian West lets lab build upon recent discoveries to advance drug design and more

Rice University chemist Julian West has won a five-year, $1.8 million National Institutes of Health Maximizing Investigators’ Research Award to advance his lab’s efforts to simplify the synthesis of organic chemicals.

The grant enables West, who joined Rice in 2019 as a Cancer Prevention and Research Institute of Texas scholar, to follow two ongoing research paths: one, to continue developing unique hydrogen atom transfer modules to streamline chemical design, and the other, to develop “mutase-like” catalysis of molecules to rapidly change and diversify their functions.

Julian West

Julian West

West introduced cHAT — for cooperative hydrogen atom transfer — last year as a method to simplify the production of alkyl fragments, building blocks in designing drugs and other compounds. The “cooperative” part involves two catalysts that react in sequence in a one-pot solution that eliminates the expensive materials used now.

“These modular processes allow us to achieve different chemical reactions or transformations to build something simple into something complex,” said West, an assistant professor of chemistry. “What we’re proposing now is pushing the envelope to add a range of applications and gain more control over processes that have traditionally been very hard.

“For instance, we want to put isotopes of hydrogen like deuterium or tritium into molecules because these are really important in pharmaceutical sciences,” he said. “Deuterium can change the properties of drugs if you put it in some positions on the molecule. It might make a drug last longer or prevent the formation of a toxic byproduct. And tritium can be useful for bioimaging and radio-tracing.”

Along the second planned path, the researchers will build upon their discovery of “artificial mutase-type” activity inspired by light-sensing bacteria that thrive near hot oceanic vents. These bacteria use vitamin B12 as a detector, performing a series of chemical reactions after absorbing light to alert them to the presence of light.

In the process, the bacteria make an alkene, a functional group of hydrogen and carbon atoms that chemists use to install new atoms on molecules. In experiments, West and co-workers found they could not only make the alkenes using vitamin B12, but also combine them with additional reactions to trigger “transpositional functionalization.” In these reactions, targeted hydrogens and functional groups can migrate to another part of the molecule while swapping out one fragment for another, allowing for atoms to be mixed and matched in ways that weren’t possible before.

“This is a completely unprecedented class of transformations,” West said.

He noted the award, to be administered by the National Institute of General Medical Sciences, is not tied to the pursuit of a particular research result. “These grants fund people, not projects,” West said. “It allows us to work on what excites us, and what we believe is going to help with human health, without having to stay within the narrow limitations of an initial project.

“From my perspective, some of the most exciting ideas we’ve had come to fruition over the last year have been from students and postdocs who’ve come to me and said, ‘You know, I found this thing I want to try,’” he said.

About Mike Williams

Mike Williams is a senior media relations specialist in Rice University's Office of Public Affairs.