Photocatalyst Used to Create a Safe, Sustainable Building Block for New Drugs

While searching for ways to use visible light to drive chemical reactions, a University of Michigan team found that by using photocatalysis, they could create a safe, inexpensive alternative to anilines, which are used for the development of new medicines.

“The problem with anilines is that they are readily metabolized by our liver, and that can create problems. We want our drugs to be metabolized, but not in a way that causes them to have toxic effects,” said professor Corey Stephenson.

The Stephenson lab uses blue LEDs to activate their photocatalysts. Courtesy of the Stephenson Lab.

To develop a safe building block for new drug development, the team began looking into structures called aminocyclopropanes. They saw the potential to convert aminocyclopropanes into 1-aminonorbornane, a compound that does not appear to be metabolized in harmful ways by liver enzymes, and that could serve as a substitute for anilines.

The team used a photocatalyst to convert aminocyclopropanes into the beneficial 1-aminonorbornane structures. In the type of photochemistry used — photoredox catalysis — the catalysts use the energy of visible light to shuttle electrons between molecules.

When the researchers mixed their photocatalyst with an aminocyclopropane and exposed the solution to LED lights, the catalyst took an electron from the aminocyclopropane, initiating the transformation process. The catalyst then gave the electron back to the aminocyclopropane, completing the reaction. Throughout the process, only light was used.

“Using traditional chemical approaches, 1-aminonorbornanes have been previously difficult to synthesize, requiring inefficient sequences of reactions and forcing inflexible conditions,” said researcher Taylor Sodano. “Now, we can do it in one step at room temperature, using visible light and environmentally friendly conditions.”

Researcher Klarissa Jackson of Lipscomb University studied the safety of the 1-aminonorbornanes that were produced. She applied the compounds to liver fragments containing the enzymes that typically metabolize drug compounds, and found that when the enzymes broke down the 1-aminonorbornanes, the process did not produce the harmful metabolites that result from anilines.

The researchers said the study is foundational work they are applying to several potential applications, ranging from epilepsy to hearing loss to cancer to fungicides.

The research was published in Cell (https://doi.org/10.1016/j.chempr.2018.10.017).