Molecular Matchmaking: Seeking fastest, sleekest reactions from ideal combinations

Molecular Matchmaking: Seeking fastest, sleekest reactions from ideal combinations

Nick Peraino, doctoral student in Health and Environmental Chemistry, researches the synthesis of gamma lactones from sulfoxonium salts in Dr. Kerrigan’s lab.
Nick Peraino, doctoral student in Health and Environmental Chemistry, researches the synthesis of gamma lactones from sulfoxonium salts in Dr. Kerrigan’s lab.

You can combine two or three molecules in thousands of ways. Associate Professor of Organic Chemistry Nessan Kerrigan, Ph.D., matches up molecules, identifying which combinations are most interesting, useful or profitable — particularly for pharmaceuticals.

Then he researches how to make their reactions happen faster.

Describing his lab’s work as “basic, fundamental, organic chemistry,” Dr. Kerrigan said, “We try to develop new ways of carrying out chemical reactions more efficiently and economically, and with an end goal in mind.”

Benefits to other researchers

Scientists outside the University might apply what Dr. Kerrigan and his student researchers uncover to develop a treatment for tuberculosis or cancer. Inside Dr. Kerrigan’s lab, though, the focus is on making the reactions between molecules happen 
more quickly, and in a more predictable manner, so that other researchers can benefit from what they learn.

Their work has been supported by two grants from the National Science Foundation and more recently, by a $333,000-million grant from the National Institutes of Health that applies through 2017.

Because of a focus on fundamentals, undergraduate students can participate in the research. This has allowed several of them to be credited in published articles.

“It expands what they’ve learned in the organic chemistry undergrad teaching lab — they just build on that knowledge,” Dr. Kerrigan said.

His group currently includes a Ph.D. student, two post-doctoral researchers and two undergraduate students.

Improving on 60 years of knowledge

In 2012, Dr. Kerrigan’s work to find a more efficient version of a reaction that researchers were aware of for more than 60 years led to publishing “Catalytic Asymmetric Heterodimerization of Ketenes” in the prestigious “Journal of the American Chemical Society”.

With that research, Dr. Kerrigan and Ph.D. student Nick Peraino identified a catalyst that would limit the number of reactions between two very reactive compounds.

“There were many catalyst systems that might work, so our challenge was to not only reduce our list of options, but to identify the best possibilities — and we did,” he said.

The goal behind that particular discovery involving beta lactones was to convert them into tuberculosis metabolites, which are molecules that have been isolated from virulent strains of tuberculosis. Other researchers can use them as biomarkers for the disease or to help develop vaccines.

Green catalysts

Much of Dr. Kerrigan’s work with catalysts is focused on organic compounds that contain phosphorus or nitrogen rather than 
faster metallics, not only because they’re less expensive, but because they’re more eco-friendly, too.

“We have to use more of the organic catalysts to generate a reaction, but we can recover, recycle and re-use them in a way that’s more environmentally responsible,” he said.

In fact, Dr. Kerrigan’s group was the first to discover that phosphorus could be used as a catalyst for ketene reactions.

Some of Dr. Kerrigan’s lab researchers are currently working to produce the tuberculosis complex molecules more efficiently. Perano is investigating how to use certain sulphur-containing compounds to make an array of biologically active compounds for industrial and pharmaceutical applications. He’s particularly interested in methods for producing reactions in a molecule that’s used by a major pharmaceutical company to produce an epilepsy treatment. Much of that work has led to publication in peer-reviewed journals.

New reactions, consistent effects

Another research area, ylide chemistry, involves researching enantio-selective and diastereo-selective reactions. As
Dr. Kerrigan explains it, most molecules can exist in two forms that are mirror images, but non-superimposable — if you place one on top of the other, they don’t match.

Because of that slight physical difference, each form produces a different biological effect in a reaction, too. Dr. Kerrigan’s research is helping the pharmaceutical industry guarantee that a reaction involving the molecules will predictably and consistently produce the desired effect.

“Our research is directed at developing new reactions and exploring some of their applications. We want to shorten the existing route in reactions already known to be useful so that other researchers can be more effective with their work,” 
he added.