UNC researchers have developed a molecule that could get medicines to market faster

UNC researchers have created a new molecule that could eventually shorten the drug development timeline for diseases and therapies.

Drug manufacturers frequently have to discard what they create as waste. The more steps needed, the more waste generated — and the process takes a lot of time.

The UNC researchers, who wrote about their work in a paper published in Science, developed a catalyst molecule that performs multiple steps at once, streamlining the chemical production process and eliminating the need for solvents to purify the chemical mixture.

“We’re trying to create the toolbox for medicinal chemists,” said Jeffery Johnson, an organic chemist who leads the research. “They need a large toolbox to create the next generation of therapeutic agents.”

How it works

The chemicals in drugs bind to proteins or other molecules in the body by assembling their three-dimensional structures in the same way that a right hand fits into a right-hand glove.

The “right” and “left” forms of molecules could be a problem if they are both made into a drug and enter the human body — one could be potent in healing disease, while the other could be idle or worse, causing health issues.

But making only one of them is against chemistry’s nature. In a chemical reaction, twin “stereoisomers” — molecules that have the same composition but different three-dimensional structures — are out in the world all at once as mixtures. If more than one isomer can be produced, controlling what chemicals are made can be difficult.

The scientists in Johnson’s lab developed a catalyst molecule can now make only one desired reaction easier to happen.

Separating the desired molecule is a slimy process because unreacted starting molecules and unwanted by-products are all mixed together. Everything is in a hot liquid mess and purifying the mixture takes substantial time and generates lots of solvent waste.

Researchers in pharmaceutical corporations frequently use the crystallization method as the final separation and purification step because it allows for large scale chemical production. A crystallization technique, like taking the salt out of saltwater, spits out the solid compound from the liquid.

The new UNC catalyst can select which molecule to solidify and which to leave behind in the solution, instead of going through many other steps to single the compound out.

According to Johnson, the new molecule could reduce the process time of scientists making chemicals because it is “a dual-role catalyst. The [same] catalyst does two different things in two different steps.”

The single-step method, according to the leading author, Pedro De Jesús Cruz, “is greener because you don’t waste a lot of solvents running the reaction, but also you don’t need solvent for the purification.”

De Jesús Cruz and Johnson hope that their catalyst will create a faster route to rapidly making complex molecules.

Johnson said developing the catalyst was a team effort. His students and colleagues “did the heavy lifting intellectually and experimentally and it’s important for me to emphasize that,” he said.