Researchers At Princeton Speed Up "A-ha" Moments

I remember my first "a-ha" moment. I'm ashamed to say it wasn't until my early teens. But then again, I was amassing the information I needed to fuel the "a-ha" moment. Since then, I've had numerous "a-ha" moments – some not as earth-shattering as others. I file them away and smile as I realize my advanced age is at least good for gaining knowledge.

Seems the "a-ha" moment is also a critical point for scientists – so much so that Princeton University researchers developed — and successfully tested — a method to speed up the chances of an unexpected yet groundbreaking chemical discovery that was sparked from the "a-ha" moment.
The researchers report this month in the journal Science a technique to accomplish "accelerated serendipity" by using robotics to perform more than 1,000 chemical reactions a day with molecules never before combined. In a single day of trials, the Princeton researchers discovered a shortcut for producing pharmaceutical-like compounds that shaves weeks off the traditional process, the researchers report.
The basis of the research was to combine new technology with a unique, rapid-reaction approach that could allow chemists to explore unheard-of and potentially important chemical combinations without devoting years to the pursuit, explained senior researcher and co-author David MacMillan, the James S. McDonnell Distinguished University Professor of Chemistry at Princeton and chair of the department. MacMillan worked with lead author Andrew McNally, a research associate in MacMillan's lab, and Princeton graduate student and co-author Christopher Prier.
"This is a very different way of approaching how we come up with valuable chemical reactions," MacMillan said.
"Our process is designed specifically for serendipity to occur. The molecules that should be combined are those for which the result is unknown," he said. "In our lab, we used this technique to make new findings in a much more routine and rapid fashion, and we show that if you have enough events involved, serendipity won't be rare. In fact, you can enable it to happen on almost a daily basis."
Illustrating that principle, the Princeton researchers combined two molecules with no history of reacting to generate the type of chemical functionality found in eight of the world's top 100 pharmaceuticals, MacMillan said. The reaction involved a nitrogen-based molecule known as an amine that has a hydrogen and carbon pair, and a circle of atoms stabilized by their bonds known as an aromatic ring.
The Princeton researchers produced numerous new reactions, but "new" does not necessarily equal interesting or important, MacMillan said. They analyzed and experimented with each new reaction for its potential application, a process that revealed the nitrogen-carbon molecule with the aromatic ring.
The research was published Nov. 25 in Science and was supported by a grant from the National Institutes of Health, and gifts from Merck, Amgen, Abbott and Bristol-Myers Squibb.

Traci Purdum
Senior Digital Editor