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Want to understand organic chemistry? Think Legos.

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In the fall of 2019, we learned that organic chemists at Ohio State had made a scientific discovery that could change the way a number of drugs are produced — possibly making it easier and quicker to produce some medicines.

The senior author of that study was David Nagib, an assistant professor in the Department of Chemistry and Biochemistry who manages a research laboratory of more than a dozen people, including post-doctorate researchers, doctoral candidates and undergraduates.

They call it the Nagib Lab and describe their work as “harnessing radicals for complex organic molecule synthesis.” Complicated for sure. But Nagib broke down that work for Insights and showed us how organic chemistry is a lot like playing with Legos. Or pairing up at a middle school dance. Or a … well, you’ll see.

How did you become interested in chemistry?

I don’t have one of these stories where I wanted to be a chemist since childhood. Based on my love of Legos, I probably would have become an architect. Then, my sophomore year in college, I took organic chemistry, where I had an inspiring teacher and was hooked on its problem-solving nature. Plus, I loved using a molecular model kit to visualize chemical reactions. It was the only class that ever gave me a three-dimensional, puzzle-like study guide.

What is an organic chemist?
I love comparing an organic chemist to an architect. Before you can build new types of buildings, you need new ways to assemble their components. Take skyscrapers — people needed to learn new ways to weld steel beams together before building these great structures. Similarly, our chemistry allows others to build complex medicines. We’re not welding the molecules for them, but we’re showing them new ways to weld it themselves.
How does this analogy manifest in your work?
In tackling a new problem, we first look at what types of bonds are hardest and most valuable to construct the building blocks of medicines. We ask: “What are the most common structures in medicine?” If we think there aren’t yet good ways to build these structures, we then ask: “Are there better ways to do it?” That’s how we choose what problems to work on.
What makes your research unique?
Our secret is free radicals. When we teach organic chemistry to undergraduates, we teach that electrons have to be paired up. It’s like a middle school dance, where all of the students want to be paired up, but sometimes there is still a lone one running around with lots of energy. We tend to think of these unpaired, free radicals as bad — they can damage cells — but the same mechanisms that can decompose things can also build things. We’ve come up with ways to harness these radicals using their energy for good — like teaching that middle schooler how to break-dance.
How does your research touch people’s lives?
Definitely through its application to medicine. For example, we recently developed a way to selectively make the most common core structure of medicines. This summer, I met a chemist who was on the team who made a cancer drug with this exact type of ring. It was their major problem in the synthesis of this drug — they were making it non-selectively and then spending a lot of resources to purify it and throw half away. Our new strategy offers a much cleaner and more efficient route to this drug — and many others.
What drives you, what’s your passion?
The reason we wake up every morning is hoping to discover new chemical reactions that others can use for discovery of new medicines. The most exciting thing is receiving an email from someone trying to use our methods to create a new medicine. I print these and share them with the team. It’s what gets us excited about what we do.
David Nagib pictured with his research team in matching Nagib Lab shirts.
David Nagib (farthest left) and his Nagib Lab research group.