Return to Emory Report home pageNew discoveries begin with dreams, believes Emory organometallic chemist Lanny Liebeskind, and the more he learns about his chosen field, the bigger his dreams grow.
As a postdoctoral student 15 years ago, Liebeskind hypothesized a new way to construct quinones, a class of molecules occurring in nature and known to exhibit a variety of biological activities. Quinones are important in a variety of vitamin compounds, and they are involved in photosynthesis in plants and in respiration, metabolism and blood clotting in animals. Chemists have discovered anti-cancer properties in some quinones, and this has led to important cancer chemotherapeutics that are based on the quinone structure. Liebeskind's unprecedented hypothesis turned out to be a very powerful chemical tool, and has blossomed over the years into new chemical methods and a variety of exciting research projects.
"Suppose you were a chemist in the pharmaceutical industry," Liebeskind ex-plained, "and you knew that quinones had anti-tumor activity, but the ones you could get from nature had minimal activity and you wanted something more active and more selective, perhaps less toxic. Many times by modifying the structure of a molecule in a controlled way while keeping part of the molecule constant, a chemist can develop very selective drugs."
In traditional organic synthesis, chemists who wanted to make quinones would start with a naturally occurring molecule that had almost all the pieces of a quinone and then make minor changes to convert this compound into a quinone. Liebeskind's idea was to break an existing quinone into two pieces, rearrange the two pieces in new ways, and use a metal to very selectively rejoin the pieces, generating the quinone structure at the point of juncture. His mainstream quinone project, titled "An Organo-transition Metal Entry to Anti-tumor Quinones," was funded by the National Institutes of Health and has been renewed for the past 15 years.
"What we have done is to give people in the academic and the pharmaceutical worlds new ways to construct quinones," said Liebeskind, who is Dobbs Professor of Organic Chemistry. He compares the process of building molecules to that followed by a creative architect. Just as the architect understands the principles of construction and the materials that are available and then combines these in creative new ways, the organic chemist knows the basic principles of building and constructing new molecules and injects his own creativity into the process.
"If you are a synthetic organic chemist and you can come up with a new reaction that people all over the world find great utility in, that is incredibly exciting and satisfying," he said.
Historically, most pharmaceuticals were made using organic molecules, but in recent years chemists have discovered that metal complexes are also useful in drug development. Cisplatin, for example, made by using platinum, revolutionized the use of metal complexes in cancer chemotherapy.
Most of the different directions Liebeskind's research has taken are based on constructing biologically active molecules using transition metals, which include elements such as cobalt, iron, rhodium, palladium, platinum and molybdenum, among others. Using these metals, the core structures are broken apart, rearranged and rejoined in the laboratory.
Liebeskind is conducting collaborative research to find ways to use his quinone chemistry to make new anti-tumor drugs based on platinum or other metals. He believes these drugs may be even more powerful and may be able to attack cancer cells through unique mechanisms.
His research also has led to a new way of making indoles, a class of molecules that in humans is important in the biochemistry of the brain. His work is attracting the interest of the pharmaceutical industry, which already uses indoles in drugs used to treat depression, sleep problems and migraines, and many other problems of the central nervous system.
Liebeskind also unintentionally has discovered reactions that are useful in constructing novel classes of organic molecules that may help him design new polymers to conduct electricity. Unlike copper wire, which breaks when it bends, these organic molecules could be used to make wire only one molecule thick, or a paste in any shape that would conduct electricity.
Liebeskind dreams of future research using organic synthesis to construct electronic switches on a molecular level. The applications of this technique to technology would be phenomenal, he says, and could lead to the ultimate in computer design. Meanwhile, he just keeps following his dreams.
-- Holly Korschun
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