RIVERSIDE, Calif. -- Aug. 18, 2005 -- Chemists at the University ofCalifornia, Riverside have synthesized a new class of carbenes --molecules that have unusual carbon atoms -- that is expected to havewide applications in the pharmaceutical industry, ultimately resultingin a reduction in the price of drugs.
Called cyclic alkyl amino carbenes or CAACs, the molecules attachthemselves to metals, such as palladium, to form highly efficientcatalysts that allow chemical transformations otherwise consideredimpossible. The carbenes modulate the properties of the metals to whichthey are bound and can facilitate and speed up reactions involvingtheir use.
Study results appear in the Angewandte Chemie International Edition, and were published online Aug. 1.
A carbene is a molecule that has a carbon atom with sixelectrons instead of the usual eight. Because of the electrondeficiency, carbenes are highly reactive and usually unstable innature.
In their paper, the UCR chemists discuss a set of chemicalreactions involving the use of catalysts other than those that areCAAC-based. The authors note that these catalysts need strong heatingto be effective. They add that the CAAC-based catalysts, on the otherhand, can be used not only at room temperature but also in smalleramounts than is necessary for the other catalysts.
"For more than a century, most catalysts were prepared usingchemical compounds called phosphines," said Guy Bertrand, the leadauthor of the study and Distinguished Professor of chemistry. "But inthe 1990s, carbenes were found to be useful to make catalysts. The newcarbenes we have prepared in the laboratory are such that they protectthe metals to which they bind, making the metal catalysts more stableand longer lasting."
Because nitrogen atoms stabilize a carbene when they areadjacent to it, chemists believed until now that two nitrogen atomswere necessary in a carbene to make efficient catalysts. But having twonitrogen atoms also imposes structural limitations at the center of thecarbene.
The carbenes synthesized by the UCR chemists has only onenitrogen atom, which lends the molecule a far more flexible structure.In effect, the carbenes are bigger at the metallic center of thecatalyst, a feature that improves the efficiency of the catalyst.
"We started this project nearly two years ago," said VincentLavallo, an undergraduate researcher in Bertrand's laboratory and thefirst author of the paper. "The carbene-based catalysts we report cansimplify complex chemical preparations. Further, just mild temperaturesare needed for the catalyst to be effective. Because of the catalyst'slongevity, you need only a small amount to achieve your final product.All of this can dramatically reduce the cost of manufacturing drugs,given that pharmaceutical companies are increasingly usingcarbene-supported catalysts for their chemical reactions."
Bertrand's research group plans to continue to modify the newcarbenes to find more efficient catalysts. "We're looking also for newcatalytic reactions facilitated by these new carbene metal complexes,"Lavallo said. "The CAACs have made the field of carbene chemistry moreexciting than ever."
Yves Canac, Carsten Pr--sang and Bruno Donnadieu of UCRassisted with the study. The National Institutes of Health and thechemicals manufacturer Rhodia provided support.
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