Molecule-making machine simplifies complex chemistry

A new molecule-making machine could do for chemistry what 3-D printing did for engineering: Make it fast, flexible and accessible to anyone.

Chemists at the University of Illinois, led by chemistry professor and medical doctor Martin D. Burke, built the machine to assemble complex small molecules at the click of a mouse, like a 3-D printer at the molecular level. The automated process has the potential to greatly speed up and enable new drug development and other technologies that rely on small molecules.

“We wanted to take a very complex process, chemical synthesis, and make it simple,” said Burke, a Howard Hughes Medical Institute Early Career Scientist. “Simplicity enables automation, which, in turn, can broadly enable discovery and bring the substantial power of making molecules to nonspecialists.”

The researchers described the technology in a paper featured on the cover of the March 13 issue of Science.

“Small molecules” are a specific class of complex, compact chemical structures found throughout nature. They are very important in medicine – most medications available now are small molecules – as well as in biology as probes to uncover the inner workings of cells and tissues. Small molecules also are key elements in technologies like solar cells and LEDs.

However, small molecules are notoriously difficult to make in a lab. Traditionally, a highly trained chemist spends years trying to figure out how to make each one before its function can even be explored, a slowdown that hinders development of small-molecule-based medications and technologies.

“Up to now, the bottleneck has been synthesis,” Burke said.  “There are many areas where progress is being slowed, and many molecules that pharmaceutical companies aren’t even working on, because the barrier to synthesis is so high.”

The main question that Burke’s group seeks to answer: How do you take something very complex and make it as simple as possible?

The group’s strategy has been to break down the complex molecules into smaller building blocks that can be easily assembled. The chemical building blocks all have the same connector piece and can be stitched together with one simple reaction, the way that a child’s interconnecting plastic blocks can have different shapes but all snap together. Many of the building blocks Burke’s lab has developed are available commercially.

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