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By Brian Petrotta
As far as scientific disciplines go, chemistry is well established. The subject as we know it today has been studied for approximately 200 years. Over that time, chemists have made staggering advances in electronics, biology, medicine and industry but, if you ask Jimmie Weaver, he will tell you scientists have just scratched the surface.
“We are at the frontier of chemistry,” he says.
Weaver is perched along the banks of this metaphorical Mississippi River, peering into the Wild West and searching for big discoveries. Over the last year, Weaver has secured a gold rush of grant money, propelling his journey to the unknown.
“It’s pure curiosity,” he says. “It’s wanting to know what no else knows yet and thinking about all the possibilities.”
Since Weaver arrived at OSU in 2012, his lab in the Henry Bellmon Research Center has focused on three distinct areas of research, each of which is now funded — at least in part — by local or national grants. He has built a stable of postdoctoral researchers, graduate students and undergraduate students from scratch and sees the possibility of expanding his team of researchers in the very near future.
Weaver’s research into carbon-flourine functionalization is funded by two separate grants: one from the National Institute of Health worth more than $1.4 million and another from the American Chemical Society Petroleum Research Fund worth $110,000. Fluorine provides the single strongest bond made to carbon, but naturally occurring C-F compounds are extremely rare (there are only 12 known out of a billion-plus compounds in the world). Weaver calls the bond the “Mt. Everest of chemical challenges” but, where others had only partially succeeded, Weaver approached the problem from a new angle and found a simple way to conquer the obstacle.
“It’s like we have the world record of climbing Mount Everest,” Weaver explains. “Where others had only achieved a reaction of 67 catalyst turnovers before the catalyst died, ours went to 25,000 before we stopped counting. Catalyst turnover is a measure of how many times a catalyst can repeat an action before it quits, so for every one of these catalyst molecules, it could repeat the reaction over 25,000 times.”
Carbon-fluorine bonds are extremely useful in creating medicines such as cholesterol regulators (Crestor), antidiabetics (Januvia), anti-HIV drugs (Emtricitabine), insecticides and agrochemicals (Diflufenzopyr). Juxtaposed against the utility of these fluorinated molecules is the difficulty of synthesizing them. Not only are the compounds rarely produced in nature, but the current state-of-the-art process for their production is long and inefficient. For instance, the fluorinated compound from which Januvia is synthesized takes seven to eight steps to make and often results in undesired environmental hazards. Most chemists have attempted to address this problem by trying to put fluorines on the molecule while Weaver realized the same goal by starting from highly fluorinated material and then selectively removing fluorines from the molecules. Fortunately, he has help with this difficult process.
Graduate student Sameera Senaweera has worked in Weaver’s lab almost from its beginning. After earning his undergraduate degree in chemistry in his home country of Sri Lanka, Senaweera spent his first semester of graduate school at OSU listening to faculty presentations before deciding on an area of study. If the above paragraphs confused you, don’t feel badly. It also happened to Senaweera at first.
“Dr. Weaver’s presentation was pretty complex,” he says, “but it was interesting.”
Senaweera also saw an opportunity to help build something from the ground up. Weaver’s lab was not yet fully realized and since Senaweera was one of his first students, there were no postdoctoral researchers or upper-level graduate students to lend assistance. The upside was that he worked closely with and learned directly from Weaver.
In fact, Weaver’s investment in his students is one of the traits chemistry department head Frank Blum admires most about him.
“Dr. Weaver works hard to support his students in their scientific work and is an example of how hard work and creativity pays off,” Blum says.
The short-term payoff has been landing federal grant money to pursue the research. The long-term benefits are potentially huge.
“Our hope is to develop chemical reactions that can be used to transform molecules of low value, such as petroleum which simply gets burned, and enhance its value by making it something you might take to save your life or perhaps use to help grow crops at a higher yield,” Weaver explains.
ELECTRON TRANSFER MEDIATED CROSS-COUPLINGS
Scaling “Mount Everest” was not enough for Weaver. He also decided to take on a group of Nobel Prize winners. In 2010, Richard F. Heck, Ei-ichi Negishi and Akira Suzuki were awarded the Nobel Prize in Chemistry for “palladium-catalyzed cross couplings in organic synthesis,” which essentially made it easier to join carbon atoms together. While this technology was quickly adopted in both research and commercial industries, Weaver theorized an even simpler solution.
“We are attempting to convince people it is needlessly difficult — at least in many cases,” he says. “We think we can accomplish many of the same transformations by the addition of an electron and we’re developing chemical reactions that allow you to do that.”
The National Science Foundation had enough faith in the idea to award Weaver a $650,000 CAREER grant in the spring of 2015. A portion of the grant funds research opportunities for undergraduates like Ryan Matlock.
A Mustang, Oklahoma, native, Matlock initially wanted to study psychology at OSU. An analytic chemistry course with Sadagopan Krishnan changed his mind, especially after spending some time in the lab. Weaver passed Matlock on campus one day and, having also had him in class and recognizing his abilities, asked if he would be interested in working in the lab.
“A week later, there I was, and I stuck with it,” Matlock says.
The hands-on experiences he developed at OSU helped him land a summer job at Accurate Environmental Labs in Stillwater. He now plans to pursue a doctoral degree and eventually start his own environmental chemistry laboratory.
“Most smart chemists don’t look at reactions like this because it doesn’t make sense,” Weaver begins.
Indeed, the first seven hits when you enter “uphill catalysis” in an Internet search all relate to Weaver’s research in some form. Yet he believes it is a mistake to overlook the potential of this process. While it is not yet simple to do, Weaver thinks scientists can get there.
Uphill catalysis refers to the flow of energy in a reaction. Generally, in a chemical reaction, molecules move in the direction that lowers the system’s potential energy, just like water flowing in a downhill direction. Weaver believes it is possible to do the opposite by using sunlight, similar to photosynthesis in plants.
“The light allows us to excite molecules, much like a windmill can pump water vertically, from this excited state all reactions are 'downhill,’ and therefore overall the products of the reaction contain more energy than the starting materials,” Weaver explains. “To do this catalytically is rare and underexplored.”
Currently supported by an Oklahoma Center for the Advancement of Science grant, his lab has engineered a molecule that contains so much extra energy that it can undergo extremely fast reactions, which can be useful for performing chemistry on large molecules (i.e. proteins, polymers, etc.). Weaver plans to add informative tools to his molecule in order to help others understand their large molecules, which can be difficult to comprehend because of their sheer size. Eventually, the hope is that this chemistry will be widely available and so simple to use that it can be put into a package to purchase from a catalog company and all that is needed is to tear, pour, and turn on the lights.
BUILDING A PROGRAM AT OSU
Undoubtedly, Weaver could have pursued a career in industry and commanded a greater salary than the one he currently collects, but the freedom to pursue a wider scope of research proved to be too enticing. He feels fortunate to hold his position at OSU, noting major pharmaceutical companies were accepting 600-700 applications for a single position at the time he was searching for a job.
Holding modern lab space in the HBRC was a major draw for Weaver as well. It offers him the tools to pursue answers to his questions, and he has developed unique skills in catching the attention of funding agencies.
“Organic synthesis researchers do not often get grants because they don’t know how to sell it,” Senaweera says. “What Dr. Weaver has learned is how to combine what we do with what the medical field or another industry is looking for.”
Weaver poured hours of work into acquiring that initial NSF CAREER award. He estimates the 15-page proposal took hundreds of hours in experiments and gathering preliminary evidence. While simply asking a question is enough to get him excited, Weaver realized he needed to take it a step further with a funding agency to really command attention.
“You have to show it is not only interesting science, but it’s going to fundamentally solve a bigger problem,” Weaver says.
Solving fundamental problems in chemistry — like scaling Mount Everest-sized chemical problems or taking on Nobel Prize winners — is the essence of what Weaver is trying to accomplish at OSU. The next challenge is to demonstrate how solving fundamental problems has huge potential impact for society. In just a few short years, he has built a team of 10 postdoctoral researchers and graduate students. That group in turn mentors undergraduates like Matlock, with all playing roles in cultivating the new chemical frontier. Though these students now handle a bulk of the hands-on work, Weaver is never far from the lab.
“He takes the time to notice when you’ve done something well,” Matlock says. “At first I didn’t know what to think of him because he liked to joke around, but he was very serious about safety and the actual chemistry itself.”
It is Weaver’s reverence for chemistry and his joy in discovering new ideas within it that spurs this chemical frontiersman onward.
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Uploaded May 1, 2016