Synthesizing a group of molecules and testing their biological applications can be difficult to accomplish in a six-week span, according to senior biochemistry major Katelyn Bercaw. To help future researchers, Bercaw spent part of her summer synthesizing several types of quinolines, a group of molecules known to have medicinal applications.
The quinoline library she constructed with Assistant Professor of Chemistry Courtney Meyet, her research adviser, will allow future research projects to focus on testing the quinolines’ effects on bacterial growth.
“The reason we were synthesizing them in the lab was twofold: Dr. Meyet worked on these during graduate school, so she knows about them and how to synthesize them, and also because of their medicinal applications,” Bercaw said.
Her project was a continuation of previous research projects involving quinolines. Last year, Stevan Lukich ’17 synthesized several quinolines and then worked with biology department chair Frank Steiner and applied them to bacteria.
“He found that they have the ability to kill MRSA, methicillin-resistant bacteria, which is cool because we’re always looking for ways to kill antibiotic-resistant bacteria,” Bercaw said.
Lukich and Naomi Virnelson ’16 both worked with quinolines to see which specific quinoline compounds would have the most impact against bacteria.
“Naomi had actually found the compound that had the most activity,” Meyet said. “Stevan also synthesized that and found it to be the case as well. What we were trying to do was to take that quinoline and synthesize quinolines like it that could increase their activity.”
Quinoline molecules consist of two connected ring structures, and the group of quinolines Bercaw worked to synthesize also have additional components that branch off from certain parts of the ring structures.
Within the quinolines’ ring structures, alternating single and double bonds contribute to the molecules’ antibacterial properties, Bercaw said. The positions of the single and double bonds cause the quinoline’s electrons to become excited when exposed to ultraviolet light, and the energy they release after exposure to ultraviolet light allows them to kill bacterial cells.
To make these specific quinolines, Bercaw used a method called one-pot synthesis, a system Meyet worked with while still in graduate school.
“She used a method that I had previously published on, so I was confident that the method would work very well,” Meyet said. “There were some compounds that she was synthesizing that I don’t believe had been tried in that combination.”
The one-pot synthesis involves adding the chemical precursors for each quinoline — in this case, an amine, aldehyde, and alkyne — to a single test tube. Under certain conditions, the molecules will react to form a quinoline with specific groups attached to the quinoline ring.
Once the reaction occurs, Bercaw used several techniques, including column chromatography, to separate the quinoline molecules from the other compounds present in the test tube.
“It’s a fairly simple process,” Bercaw said. “Getting the column to run is probably the most challenging step because you have to get a feel for how the different materials separate.”
Bercaw said she was able to successfully make nine different quinolines for future researchers to use in their own projects. She initially struggled to isolate pure quinolines, and found that other unwanted compounds were mixed in with her product. Meyet said they were able to identify the problem about halfway through the project: a stabilizing compound that was mixed in with one of the chemicals they used in the synthesis.
“At least we have that issue worked out, so when it’s time for others to go and synthesize, we hopefully won’t run into that same issue,” Meyet said.
Junior Rosemary Pynes said she will be continuing Bercaw’s work in some capacity next summer, either by synthesizing additional quinolines using the same method as Bercaw or by testing the quinolines Bercaw synthesized to see how they will impact bacteria.
Bercaw, who plans to attend pharmacy school next year, said she enjoyed working on the project this past summer.
“It was fun to work with Dr. Meyet and just be dedicated to one thing in a way that we aren’t able to when we’re doing labs for classes,” Bercaw said.