Apr. 22, 1998 By DAVID WILLIAMSON, UNC-CH News Services
CHAPEL HILL -- An "elegant and clever" new technique for developing more effective catalysts for chemical reactions has been invented by University of North Carolina at Chapel Hill scientists.
The method, which employs a burgeoning science known as combinatorial chemistry, enables technicians to screen thousands of catalysts simultaneously and in a fraction of the time it used to take. Potentially, the method will be "extremely general," one expert predicts.
A report on the research appeared in the April 10 issue of the journal Science. Authors are doctoral student Steven J. Taylor and Dr. James P. Morken, assistant professor of chemistry.
"A chemical reaction is basically an interaction between two or more compounds to produce some useful product, and a catalyst just speeds up the reaction or makes it possible," Morken said. "Within about the past five years, almost every drug company in the world has started using combinatorial chemistry to discover new drugs. Now, we have applied that approach, pioneered by Mario Geysen of Glaxo Wellcome, to finding catalysts.
"With more efficient catalysts, just about any process could be improved, including fuel emission controls in a car, solar energy harvesting, preparation of cheaper drugs and converting bulk natural resources into useful products such as polymers and plastics."
In the past, chemists identified catalysts through trial and error and then, over sometimes years or decades, changed their structure to boost their function. The new technique employs infrared thermography -- a way to measure heat -- to screen many compounds at once.
"Police departments use infrared devices to pick up heat produced by children lost in the woods," Morken said. "Similarly, we use a thermographic video camera to find which polymer beads -- to which chemicals have been attached -- are generating heat. That heat indicates a chemical reaction, and the more heat, generally the better that chemical is as a catalyst."
Using the eye of a needle as a ladle, researchers scoop out the hottest beads from the laboratory glassware where reactions occur. Then, to learn what catalysts may have been discovered, they analyze all recovered beads with a decoding technology developed at Columbia University. Finally, in separate, more conventional experiments, they confirm that the catalysts work as expected.
As an example of combinatorial chemistry, Morken said that if he had a catalyst made up of three different chemicals, he could make 50 variations of each chemical and stick them to the polymer beads. Combining 50 of one variant with 50 of another, he could create through a multiplier effect 2,500 possible reactions. Adding the third chemical variant would multiply the number of possible reactions -- and catalysts -- to 125,000.
The thermographic video camera method allows researchers to "cook" the beads bearing different chemicals in the same laboratory vat. Fishing out promising beads is comparable to fishing out tasty chunks of meat from a pot of beef stew while ignoring the nearby vegetables.
"With combinatorial chemistry, you can make 100,000 compounds in about two weeks," Morken said. "It shouldn't take our assay a whole lot longer than that to screen those. We believe this work is going to have a large impact on the catalyst discovery process."
In the successful experiments reported in Science, the UNC-CH chemists created as a test system, a simple reaction related to those occurring in the body and catalyzed by enzymes.
Morken's former colleague at Harvard University, Dr. Nathaniel Finney, called the new method "amazing."
"This is the most significant advance yet reported in the application of combinatorial methods to the discovery of new highly active catalysts," said Finney, assistant professor of chemistry at the University of California at San Diego.
"While the synthesis of polymer-bound catalysts has a long history, the simultaneous evaluation of mixtures of catalysts has remained an elusive goal," he said. " Morken and Taylor have provided an elegant, clever solution to this screening problem, and one which promises to be extremely general."
The UNC-CH scientists have applied for a patent on their new method, which already has been used to screen 3,150 potential catalysts.
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