Summer Research Creates New Chemical Compounds

In the mid-1970s Point Loma Nazarene University began offering research opportunities to undergraduates. Every summer, STEM students gather to research “fascinating subjects in compelling settings”. The program is designed to prepare students for the “research aspects of graduate and medical school”. More importantly, summer research programs provide a “unique experience and expertise” that employers notice. The variety of research opportunities offered by PLNU is a “rare commodity”. Students are trusted with “advanced” equipment to study questions proposed by a Principal Investigator (PI)–an expert in their field.

One of these projects has been ongoing for years. It began when Marc Perry, PhD, noticed a pattern with the catalysts – something that “speeds up” a reaction – he was using for a process called Kumada coupling – where two organic molecules are bonded together. When the catalyst is nickel, Dr.Perry observed the reaction proceeds only if a nonpolar solvent, like diethyl ether, is used. If the catalyst is iron, a polar solvent, like dioxane, is needed for the reaction to occur. At the time, it was unknown which catalysts required a dioxane or ether solution. Dr.Perry turned to his advanced organic chemistry class to answer this question. 

Within a quad, Dr.Perry’s class identified catalysts that can facilitate Kumada coupling in a dioxane and/or diethyl ether solution. The catalysts that depend on dioxane intrigued Dr.Perry because chemists can use the chemical environment to push the reaction forward, making it more  effective. With this information, Dr.Perry wanted to see if the traditional method of Kumada coupling could be improved. After years of research, the work of Dr.Perry and his students is now known as “Cobalt-Catalyzed Kumada Coupling of N-aryl chlorides.” 

This summer was Allion Eazell’s, a research associate on the project, first experience conducting research. 

“It never felt like work, it was just fun,” Eazell said.

The summer research program offered Eazell a chance to engage with classmates and faculty at a personal level saying, “the part that stood out the most were the connections”. Eazell said the research at PLNU is different from other programs for the better. 

“I ask a lot of questions, and normally your PI isn’t around as much as they are here,” Eazell said.

 As a result of her experience, Eazell chose to work as a lab assistant this year. 

Kumada coupling is a subset of cross-coupling reactions. The process consists of three parts: oxidative addition, transmetalation, and reductive elimination. In simpler terms: you stick a molecule onto a metal atom, stick another molecule next to it, and then you pull them off together. The metal used in the reaction is the catalyst. The catalyst draws two molecules close together, enabling them to bond to each other. Without a catalyst, molecules rely on spontaneous collisions to react. Catalysts organize the molecules in such a way that they are more apt to bond, allowing reactions to take place in hours instead of years.

The chemical industry relies heavily on nickel and palladium to catalyze Kumada coupling. Dr.Perry wanted to find a potential substitute that was cheaper and less toxic. From the list produced by his students, Dr.Perry’s research team chose to research cobalt because it was the  cheapest and most efficient. The goal was to study Kumada coupling with aryl chlorides–a notoriously difficult molecule to couple. Specifically, N-aryl chlorides (an aryl chloride containing a nitrogen) were researched because of their potential use in medication.

This past summer marked the end of Dr.Perry’s multi year research project. The endeavor was a success. Dr.Perry and his team of undergraduates ran countless reactions and managed to attach a variety of carbon chains to a diverse set of aryl chlorides. Currently, the group is compiling a data table listing each reaction and their efficiencies. 

As a result of their research, eight novel compounds were discovered. Eazell explains: “We essentially made new compounds that’ve never been made before”.  

Dr.Perry’s group also found the addition of water makes the reaction more efficient. Kumada reactions are usually dry, and the team’s discovery may prove useful to chemists in the future. 

“It’s been a fun project. And this addition of water was really unique.” Perry said. “We’re just contributing a small piece to the broader puzzle. And if anyone wants to make carbon-carbon bonds with N-aryl chlorides, this would be a good, cost effective way to do it.”

By: Jakob Vucelic-Frick