New Molecules, New Discoveries

Molybdenum—it’s a metal, and it plays a crucial role in biology. Molybdenum isn’t as well-known to the public as iron or zinc, and it’s not likely that one would take a dietary supplement for molybdenum deficiency. But it’s a metal that’s important for human health, and it’s the focus of Dr. Sharon Burgmayer’s research.

Burgmayer, Dean of Graduate Studies and the W. Alton Jones Professor of Chemistry, specializes in bioinorganic chemistry, which concerns the function of metals in biology and biochemistry. She’s been studying molybdenum since she arrived at Bryn Mawr 31 years ago. “Humans don’t need large quantities of molybdenum, but it’s critical for neurological development,” says Burgmayer. “One of its most important functions is detoxifying sulfite, which is a bi-product of the body’s normal bio-chemical processes. Molybdenum turns sulfite into sulfate, which is not toxic.”

“Molybdenum can also activate certain drugs,” continues Burgmayer. “Some pharmaceuticals are designed to chemically change once in the body. A new molybdenum enzyme was recently discovered in humans that makes certain types of pharmaceutical molecules become active.”

The types of reactions that occur at the atomic level within the molybdenum enzyme, which make this activation possible, are at the center of Burgmayer’s research.

Burgmayer’s lab at Bryn Mawr is one of the few labs in the world that examines a particular molecular structure attached to the molybdenum atom (Mo) in the molybdenum enzyme, called pterin, where important reactions occur. Says Burgmayer, “I’m interested in what happens when the Mo atom is linked to the pterin. For instance, how does this Mo-pterin pair behave when we add or subtract electrons?”

To answer such questions, Burgmayer utilizes a modeling approach to research. As Burgmayer puts it, she and her research team “mix things up and make new molecules” that serve as models for experiments. It’s a process called synthesis. In 2012, Burgmayer’s team published the synthesis of a molybdenum and pterin molecule that was stable enough to run experiments on. This was no small feat.

It took 15 or 20 years to synthesize a useful molecule model. Burgmayer and her team were the first researchers in the world to do so. “After devoting decades to creating this model compound, we really celebrated.” remarks Burgmayer. “Now, the goal is to use this model to better understand the enzyme behavior.”

The application of Burgmayer’s research to the development of pharmaceuticals is one example of how bioinorganic chemistry has become more relevant in recent years. Despite its increasing importance, she expresses some concerns. “The number of chemists doing this kind of research is dwindling,” says Burgmayer, “and it’s become harder to get funding for the type of synthetic chemistry I do.”

Burgmayer’s work has been supported by the National Institutes of Health and highlighted by the Journal of the American Chemical Society and Inorganic Chemistry. Over the three decades she has been pursuing bioinorganic research at Bryn Mawr, she has mentored 130 undergraduate and 16 graduate students.