In partnership with the NIH: The David MacMillan Group and photoredox catalysis

One of the great strengths of the MacMillan Lab is its ability to find connections between unrelated processes that no one else finds and merge them to enable chemistry that no one else imagines.

In a nutshell, that describes photoredox catalysis, the pioneering, reaction-driving, light-based technique that David MacMillan introduced to the world of organic chemistry in 2007.

The linchpin of that innovation is the National Institutes of Health (NIH), an early backer of MacMillan when photoredox catalysis was still just a really good drawing-board idea. “The support we’re given by the NIH, we know this is a privilege,” said MacMillan. “The outcome of these investments go right back into the public sector. It belongs to the public.”

Today, nearly 3,000 researchers around the world have cited the Science paper introducing photoredox catalysis. It’s used globally to drive new reactions with abundant molecules. Pharmaceutical companies replaced old orthodoxies with the process to create a new world of therapies. It democratizes chemistry in a way few others have with a generalized approach that can be used by any chemist with a lightbulb. It is a game-changer for synthetic organic chemistry.

Would this have been possible without NIH funding? MacMillan says simply: “No.”

What is photoredox catalysis?

In photoredox catalysis, chemists shine blue LED light—cheap, regular, available everywhere—on otherwise “disinterested” molecules in a vessel that contains a catalyst. The catalyst absorbs energy from the blue light and instantly becomes the equivalent of a 32,000-degree energy source … which makes things happen. It energizes otherwise stable, “boring” molecules to an activated state, causing them to click together like Legos and create new combinations that can be mined for new chemistry. The process invites an almost limitless pool of previously unreactive molecules to the bench.

The scientific world has known about the value of photochemistry since the 1970s. What it didn’t know, and what the MacMillan Lab came up with, was that combining traditional photochemistry with synthetic organic chemistry and catalysis can drive chemical reactions that were previously impossible.

What does “photoredox catalysis” mean?

The contraction “photoredox” invokes the chemistry of electrons. The blue light excites the catalyst and the resulting energy means molecules suddenly become reactive, or eager to do some interesting chemistry. That means either taking an electron (“reduction”) from another molecule or giving one away (“oxidation”) to create a whole new molecule.

How does this research impact the public?

Photoredox catalysis has spurred a throng of new drug therapies, fine chemicals, agrobusiness products, and fragrance applications. Discoveries continue in academia and in industry throughout the world.

What do peer scientists think about photoredox catalyis?

James McCusker, MSU Research Foundation Professor, Department of Chemistry, Michigan State University: “In the early days of photoredox, the prevailing sentiment typically went along the lines of: ‘It has been known for decades that MLCT states can engage in electron transfer chemistry,’ to which I would always reply, ‘Well, did you think to use them for synthetic organic chemistry? Because I sure as hell didn’t.’ It literally changed the face of synthetic chemistry. Looking beyond academia, it is virtually impossible to overstate the impact photoredox catalysis has had on the chemical industry.”

Tehshik Yoon, Professor, Department of Chemistry, University of Wisconsin-Madison: “One would be hard-pressed to find a university chemistry department anywhere in the world where photoredox catalysis is not being studied. [And] every major pharmaceutical company has recognized the new synthetic capabilities unlocked by photoredox catalysis and is actively incorporating reactions developed in MacMillan’s lab into their workflows. The first commercialized medicines manufactured using photoredox catalysis have just hit the market. The impact of his research has fundamentally reshaped the landscape of modern organic chemistry.”

In partnership with the NIH:

“Photoredox was an odd way of looking at chemistry: you’re going to shine blue light on things? A lot of people were skeptical. But the NIH was not,” said MacMillan. “They got behind the idea, funded it, encouraged it. The NIH lets great scientists, really creative people, do their work. It’s a true meritocracy and it’s based on a very competitive process. You have to prove the value of your idea. It is literally one of the engines that’s made America become so successful.

“You know, academics don’t become academics to waste people’s money. We’re genuinely driven by what is possible, what we can invent, and what we don’t know that we can find out to benefit the world. The NIH asks, who are the best people in the world going after these areas, and then it gives you the freedom to build out your best ideas. I couldn’t have accomplished a fraction of what I’ve done without the NIH.”