Wielding Visible Light to Build Molecules

Yoon Group Photochemistry
The Yoon group uses visible light to build molecules that are mirror images of each other, like right and left hands. The challenge is to selectively build a selected molecule and not its mirror image.

Reactions that are driven by light, termed photochemical reactions, were first described in the early 1800s. More than a hundred years later, organic chemists are still learning how to use light to synthesize complex molecules.  Because the sun is an abundant source of clean and renewable energy, the ability to use light, in particular visible light, to synthesize our chemical materials would yield significant environmental benefits.

However, photochemical reactions are notoriously difficult to control. A typical photochemical reaction generates a mixture of products with varying 3-D structures. The differences between the products can be very subtle: the molecules can be chemically similar yet mirror images of each other, like right and left hands. The opposite 3-D structures often lead to drastically different biological activities, and methods that can selectively build a single mirror image of the product molecule are needed.

In a study published today in the journal Science, Professor Tehshik Yoon and colleagues report a new strategy that provides unprecedented control over the 3-D structures of molecules that are made with visible light.

Professor Tehshik Yoon
Professor Tehshik Yoon

“I think there was a prejudice in the synthetic field for a long time that when a molecule absorbs energy from a photon, it becomes really reactive and the resulting reaction is difficult to control,” Yoon says.

Rather than simply trying to control the excited molecule, the Yoon group found the key is to make the photoexcitation step more selective. Most photochemical reactions are induced with ultraviolet (UV) light, which is relatively high in energy and can efficiently drive photochemical reactions. However, since most organic molecules can absorb UV light, the photoexcitation step is not selective, leading to background reactions that generate products with undesired structures. Yoon proposed that if visible light could be used instead, chemists would have more opportunities to control the reactions.

Former Yoon group graduate students Michael Ischay (Ph.D. ‘11), who is currently a chemist at Gilead Sciences, and Juana Du (Ph.D. ‘12), now a postdoctoral fellow at the University of California, Berkeley, developed a new method to speed up photochemical reactions with visible light. To drive the reaction, they chose a ruthenium-based catalyst that has been used extensively in solar energy conversion systems. Notably, the reaction also requires a second catalyst that selectively activates the starting material. This duel-catalyst strategy prevents background reactions, and Du found that she could adjust the second catalyst, which binds the starting material, to guide the 3-D structure of the final product.

Yoon group members Kazimer Skubi, a graduate student, and Danielle Schultz, a postdoctoral fellow, collaborated to optimize the strategy.  They synthesized and tested many catalysts to find the one that provides the most structural control. Their work led to the first photochemical strategy with visible light that can be controlled to produce a single mirror image of their target molecule.

For the study, the Yoon group focused on a type of photochemical reaction that generates cyclobutane structures—four carbon atoms connected to form a square ring. This type of molecular structure can only be created by using light.

“About 1,700 known natural products have cyclobutane rings in them, and the number keeps increasing as more are found in nature,” Yoon says. “We need techniques to create the same kinds of molecules [as nature does]. Otherwise we are missing out on all of that biological activity that could be harnessed for new medicines or new materials.”

With a functional strategy to control visible light for chemical synthesis, Yoon looks to expand the platform for discovering other new photochemical reactions. He believes “the door is wide open now.”

Story by Grace Pham, communications project assistant