Light as a Chemical Tool

A blue light commonly used in fish tanks and indoor gardens could help chemists solve one of drug discovery's biggest challenges: building more intricate molecules without adding costly reaction steps.

Many medicines are based on small carbon-rich molecules. Their biological effects depend heavily on their shape — more three-dimensional molecules can fit biological targets with greater precision, improving potency and selectivity. But making those complex shapes usually takes extra time and materials.

The Breakthrough

Researchers led by the University at Buffalo have developed a visible-light reaction that makes two neighboring changes to a molecule at once. The study, published July 9 in Science, uses blue LEDs, a light-sensitive catalyst, and widely available carbon-halogen compounds.

Normally, when chemists remove a halogen from a molecule and replace it with something else, the reaction only changes the carbon that held the halogen. This new method reaches the carbon next to it as well.

"We've used the relatively mild conditions of visible light to expand what chemists can do with a longtime organic chemistry staple," says corresponding author Patricia Z. Musacchio, PhD, assistant professor of chemistry at UB.

Why Two Carbons Matters

Carbon atoms form the framework of most small-molecule drugs. For medicinal chemists, each useful modification can reveal whether a candidate molecule binds more strongly to its target. But every additional reaction also creates opportunities for low yields or chemical failure.

Combining two modifications into one reaction saves more than a single laboratory step — it reduces the number of intermediate compounds that must be produced, isolated, and tested.

"More changes in fewer steps is crucial when creating small-molecule drugs," says co-corresponding author Jennifer Hirschi, PhD, associate professor of chemistry at Binghamton University.

The "Buffalo Boxes"

The experiments take place in small illuminated compartments called "Buffalo boxes" that line the shelves of Musacchio's lab. Each box contains blue LEDs similar to those sold for fish tanks. Vials inside receive controlled light exposure, activating the catalyst and starting the reaction.

Visible light is important here. UV light — commonly used in photochemistry — can degrade or decompose the organic molecules being created. Blue light is a much milder approach.

Implications

The team plans to work with pharmaceutical companies to adapt the reaction for real drug targets. The hope is not just to make drugs faster, but to make more complex drugs that can target challenging medical goals that simpler molecules cannot reach.

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