Paul Chirik Source: C. Todd Reichart, Department of ChemistryChemists from Princeton University and Merck & Co. Inc. have found a revolutionary way to produce an epilepsy drug with materials that are cheaper, work faster and are more environmentally friendly than the precious metals currently being used.

“This highlights an important principle in green chemistry — that the more environmental solution can also be the preferred one chemically,” said Paul Chirik, the Edwards S. Sanford Professor of Chemistry and head of the lab that produced the research. He and his team initially began working about 10 years ago to find replacements for platinum, rhodium and other precious metals based on cost but discovered substitutes that also have a smaller environmental impact.

“There are huge environmental concerns, if you think about digging up platinum out of the ground. Typically, you have to go about a mile deep and move 10 tons of earth. That has a massive carbon dioxide footprint, ” Chirik said.

One of the main issues is that molecules have right- and left-handed forms that react differently, so the Food and Drug Administration requires that medications are single-enantiomer drugs, meaning they only contain one “hand,” for safety reasons. The challenge for chemists is synthesizing only one hand. Precious metals are used as catalysts for this purpose.

“Our paper demonstrates that a more Earth-abundant metal, cobalt, can be used to synthesize the epilepsy medication Keppra as just one hand,” Chirik explained.

Another issue is that the use of solvents contributes a large amount of waste to the process of manufacturing drug molecules. The switch to cobalt allowed for the use of methanol, a less toxic solvent, to conduct the reaction, rather than the chlorinated solvents, such as dichloromethane, that rhodium requires, thereby furthering the goal of finding a greener method of producing medications.

Both Chirik and Michael Shevlin, an associate principal scientist at the Catalysis Laboratory in the Department of Process Research & Development at Merck & Co. Inc. and a co-author on the paper, credit the academic-industrial collaboration with the success of the research.

“Instead of trying just a few experiments to test a hypothesis, we can quickly set up large arrays of experiments that cover orders of magnitude more chemical space,” Shevlin said. “The synergy is tremendous; scientists like Max Friedfeld (the first author on the paper and a former graduate student in Chirik’s lab) and Aaron Zhong (co-author and graduate student) can conduct hundreds of experiments in our lab, and then take the most interesting results back to Princeton to study in detail. What they learn there then informs the next round of experimentation here.”

The research was published in the journal Science on May 25.