An aha moment. A cry of eureka. There are many ways to describe what happened in Associate Professor of Chemistry Max Majireck’s lab on that day in late June 2016, but, by his own admission, it was most likely a once-in-a-lifetime experience — the discovery of a novel and potentially valuable class of compound known as pyridinium ketene hemiaminals.
This summer, after six years and the help of more than 30 Hamilton student researchers, Majireck received a $247,000 grant from the National Science Foundation to continue building on that foundational discovery. He and his latest crop of students are working to develop new types of reagents, substances used to facilitate a chemical reaction such as the synthesis of pharmaceutical products (i.e., antibiotics).
Like many great things, Majireck’s discovery happened by chance.
Over the past 80 years, only a few scattered reports had been published on compounds similar to those that would first be identified in Majireck’s lab. Since most were found to be unstable, little follow-up research had been conducted despite their potential for useful applications.
Majireck and his student researchers initially discovered this new class of compound by mistake. They were attempting to synthesize a natural product with anti-HIV activity. Although that specific experiment failed, the group identified an interesting side product — the first example of a pyridinium ketene hemiaminal that was also, surprisingly, stable.
It took a while longer to determine the identity of this mystery compound with absolute certainty. The Majireck team gathered an extensive set of data using both standard and advanced techniques in nuclear magnetic resonance, infrared spectroscopy, and mass spectrometry. “We had to be extra skeptical of our own interpretations of this data, given the unusual nature of the finding and predicted instability of this new compound,” Majireck recalled in a 2018 news article. “And there were some other possibilities that we could not rule out with our data alone.”
Majireck reached out to his undergraduate mentor Charles Kriley, a professor of chemistry at Grove City College. Known for his expertise in x-ray crystallography, Kriley described the structure determined from his x-ray data. Due to the rarity of this initial finding, Majireck and his students expanded their research to include other examples of this compound class. They collaborated with Eric Reinheimer, a crystallographer at Rigaku Oxford Diffraction, who had access to state-of-the-art x-ray diffractometers. The high-quality data generated by Reinheimer unambiguously proved the structure of this rare compound.
In the meantime, Majireck’s lab began optimizing a protocol for synthesis of pyridinium ketene hemiaminals and expanded the scope of their protocol to include multiple compounds having similar structures — all but one were found to be stable. Yet the question remained ... why?
The answer came from someone right next door: Associate Professor of Chemistry Adam Van Wynsberghe, an expert in computational, theoretical, and physical chemistry. By computationally modeling the structure and dynamic nature of these compounds (i.e., how the molecule moves), the researchers gained further insight into the chemical behavior and stability of these compounds that could not be obtained otherwise.
Majireck’s deep dive into discovery is what ultimately led to the National Science Foundation grant; his work on the project is only beginning. He and his students have already expanded the availability of this understudied but highly valuable material for future research. In addition, they have identified multiple new reaction types involving the compounds, which they believe will be adopted by other synthetic chemists for a range of new applications such as drug or material synthesis.
“I’m particularly proud that such a large team of undergraduates contributed to this project over the years,” Majireck says. “It’s a testament to their hard work and skill in the lab that every new student who joined the project could easily replicate the results of prior students. They developed a robust set of procedures that both a novice and experienced chemist can execute.”
Since joining the Hamilton faculty in 2013, Majireck has made it a priority to engage students in research. They have presented alongside him at the National Meeting of the American Chemical Society and appeared as co-authors in such academic journals as Molecules and The Journal of Organic Chemistry. As a first-generation college student who admittedly had some difficulties adjusting to college himself, Majireck understands the power of scientific inquiry and creating opportunities for his students.
“Research provided me with a safe haven. The lab is a place where there’s always the potential to do something unique,” he says. “When my students have those moments when the lightbulb goes off — that energizes me. It’s incredible to be a part of that. It’s the reason I do research and the reason I teach.”