Molecules Are the Message
But collaboration among biologists and chemists is needed
Two new chemistry professors joined the faculty last year, bringing fresh energy and diversifying the areas of research in the young department.
Assistant Professor Oleg Larionov’s expertise is in the synthesis of natural products with anticancer properties, and Assistant Professor Zachary Tonzetich is studying transition metals as catalysts and in certain interactions within the human body.
“They have fire in their bellies,” says Department Chair Professor Waldemar Gorski. “They want to achieve things.”
Fighting Cancer with Nature
What do those white, crusty patches on pumpkins and a rare African tree have in common? Both possess tiny amounts of natural products that Larionov, an organic medicinal chemist, believes could be the key to new anticancer drugs.
But before researchers can even begin their quest to create a new drug, it takes chemists to crack the code to substances in nature that can be both difficult to access and extremely scarce in order to make them in the lab. These natural products are chemical compounds made by organisms living on land or in the sea. They are essentially chemical weapons to ensure the organism’s survival. “They develop this very exquisite method of defense: They produce these chemicals which are toxic to their predators or competitors,” says Larionov.
Isolating and then synthesizing molecules which harbor this medicinal firepower is where Larionov’s lab comes in. Identifying natural products with anticancer activity and then creating versions of those compounds in the lab will allow scientists to further study the compounds and develop drugs effective in humans. Larionov points out that 63% of all new drugs between 1980 and 2008 were natural products, their derivatives or inspired by natural products. The same can be said of 70% of all cancer drugs developed since 1940.
Larionov comes from Harvard University, where he worked as a postdoctoral fellow with Nobel Prize-winner E.J. Corey. Their research established a strategy for making molecules of natural products in the lab—essentially providing a roadmap for researchers to create their own supply for further study and testing. One of the natural products they synthesized came from a pink coral near Hawaii. “So that is one of the reasons we make these natural products, because very often they are produced in very small amounts by organisms that live very far away,” Larionov says. “Somebody went there and took this coral, extracted this natural product, characterized it and found it was biologically active, but for biological tests we need much more of this compound than this organism produces, and so we need to make more.”
The Max and Minnie Tomerlin Voelcker Fund is supporting Larionov’s research at UTSA with a $300,000 grant. His lab is making molecules of natural products produced by the Roridium microorganisms—the patchy growths on pumpkins and other vegetables—and by the Brucea antidysenterica tree in Africa.“We are going to synthesize these compounds,” Larionov says. “We are particularly interested in compounds which exhibit very interesting anticancer activity. We will try to make more of these compounds and develop a reliable route so that somebody else, when they need to make these compounds, can find the procedure and just follow our protocol to make the compound and test it—or they can ask us to make it, to collaborate.”
The process will involve plenty of collaboration during a back-and-forth among chemists and biologists in which the compound is tweaked to improve its potency and minimize side effects.
“It is very multidisciplinary research,” Larionov says. “A lot of people with different expertise in different fields collaborate. That is what research nowadays is. You need people with vast knowledge in different fields.”
Expanding the Knowledge Base
The power to create something new drew Tonzetich to chemistry. The inorganic chemist joined the department in the fall of 2010, after completing a National Institutes of Health postdoctoral fellowship at MIT, where he worked with renowned inorganic chemist Stephen Lippard.
The major research projects underway in Tonzetich’s lab involve transition metals such as iron, copper, cobalt and nickel.
During his first year at UTSA, Tonzetich received a three-year, $150,000 grant from the Welch Foundation in support of his research into how hydrogen sulfide interacts with transition metals in the body. Tonzetich’s lab makes molecules to study these interactions. The goal of his research is to gain foundational knowledge that could one day be used to develop drugs to fight disease.
“It is a very toxic molecule,” Tonzetich says of hydrogen sulfide, “and is responsible for the smell of rotten eggs. But in small quantities, hydrogen sulfide is produced in our bodies and can play a physiological role.”
Fundamental chemistry is the first stage of this project, he says. “We are lacking the fundamental chemical knowledge of how it interacts with transition metals. That is what I think we can contribute to this whole question.”
The other major project in Tonzetich’s lab is geared toward learning whether iron can be substituted for palladium as a catalyst in carbon-carbon bond-forming reactions. These reactions are used to make materials ranging from pharmaceuticals to polymers. Finding a more efficient catalyst would have multiple benefits including lower cost and less environmental impact.
“Palladium has a number of drawbacks,” he says. “Its high cost is the No. 1 [drawback], and it’s also a toxic element. So we are asking the question, ‘Can we take reactions that are known to be catalyzed by palladium metal—these carboncarbon bond-forming reactions—and can we realize the same chemistry using catalysts based on iron?”
By early summer, Tonzetich’s lab group had already made several iron-containing molecules that were either catalysts or precatalysts and were preparing to study their reactivity with other molecules.
“If we move from a metal like palladium to iron, we are talking about all those benefits plus lower cost, plus lower environmental impact, and since the supply of iron is not as small as that of palladium, it is also, in my opinion, a more sustainable way of achieving these reactions as well,” he says.
In addition to their enthusiasm, both Larionov and Tonzetich are wellconnected in the field.
“I am very happy they joined UTSA,” Professor Gorski says. “Any good addition makes our prospects of success better. This is what we want: Young people wanting to achieve, hungry, with great pedigrees— and great contacts, which help.”
The capacity for creativity in chemistry drew Tonzetich, the son of a biology professor.
“Chemistry is one of the few fields of science where we are creating new things,” he says. “In many fields of science, we are studying what already exists; we are studying the earth; we are studying the processes of the body. In chemistry, we do that to a large extent as well, but we also have the potential to create new molecules, things that nature would have never created or which have never been created and therefore have completely unknown reactivity, completely new. That’s a very awesome power, to be able to create new things like that.”