New Chemical Discovery Could Make Medicine and Manufacturing More Sustainable

Scientists at The University of Texas at Austin have developed a new chemical method that could make it easier, safer and more environmentally friendly to create medicines, agricultural chemicals and other important products. Their research, recently published in Nature Chemistry, introduces a greener way to link carbon atoms together, an essential step in making many complex molecules.

“This discovery is about making chemistry cleaner, cheaper and more efficient,” said Michael Krische, a professor of chemistry and holder of the Robert A. Welch Chair in Science, who led the study. “We found a way to skip some of the most hazardous steps in traditional methods and replace them with something much safer.”

At the core of the new method is a reaction called cross-coupling, which is used to form carbon-carbon bonds. These bonds are found in nearly every small-molecule drug approved by the FDA, including common medicines such as aspirin and antihistamines. Normally, cross-coupling requires sensitive and hazardous organometallic compounds, which are expensive to make and generate a lot of waste.

Instead of relying on these risky materials, the team discovered a way to skip the dangerous steps by using sodium formate, a cheap, safe and ecologically friendly substance. This breakthrough makes the entire process greener and more practical for industrial use.

“This technique could change the way chemists build new materials, medicines and industrial chemicals,” Krische said. “We’ve already seen strong interest from industry, including companies that make pharmaceuticals.”

Sodium formate transfers hydrogen atoms, and it is commonly used for de-icing, as a preservative in animal feeds and cosmetics and in the textile industry. One of the biggest challenges of the project was understanding precisely how the reaction worked. In the middle of the study, the team discovered that a key ingredient they thought was essential—the ligand—was unnecessary and later they discovered the ideal catalyst for the reaction is a palladium(I) dimer.

“We improved one of the most commonly used chemical reactions by taking out a harmful component and maintaining its efficiency,” said Yoon Cho, a UT graduate student and first author of the study. 

Yu-Hsiang Chang, another UT graduate student and co-author on the study, began optimizing the reaction in 2022 and played a key role in identifying improvements such as using water as a co-solvent and confirming what drove the reaction. Peng Liu, a faculty member at the University of Pittsburgh, provided computational data. 

Krische’s pioneering work in hydrogen-based chemistry recently earned him the Yamada-Koga Prize, one of the highest honors in organic chemistry. The award recognizes scientists whose research has transformed the field. He is the first researcher from Texas to win the award.

“Prior recipients of the Yamada-Koga Prize are among my biggest chemistry heroes,” Krische said. “Being named alongside them is truly the biggest honor of my career.”

His work has fundamentally changed how chemists think about hydrogenation, a chemical process used in everything from food production to drug manufacturing. Over the last two decades, Krische and his team have developed entirely new ways to build molecules using hydrogen transfer, which eliminates waste and makes chemistry more sustainable. The study out this week provides a key example.

“Like any major discovery, this is just the beginning,” Krische said. “We’re excited to see how others will build on our work and find new ways to make chemical synthesis cleaner and smarter.”

Zachary H. Strong, Zachary J. Dubey and Seoyoung Lee of UT; Kevin P. Quirion and Liu at the University of Pittsburgh; Nam Nguyen and Nicholas A. White of Genentech; and Natalie S. Taylor and Jessica M. Hoover of University of Minnesota - Twin Cities were also authors on the paper. The research was funded by the Robert A. Welch Foundation, the National Institutes of Health, Genentech and the National Science Foundation.