Many molecules, especially biological molecules, have a property called handedness, or chirality, whose impact on such things as synthetic drugs has been known for many years. When synthetic drugs are made to mimic natural products, they must have the same "handedness" as the molecule of the original plant or animal to have the same beneficial effect. If the synthetic drug has the opposite handedness, it can have undesirable side effects. The drug Thalidomide, for example, wreaked havoc because, as a synthetic drug, it unexpectedly took on both chiral properties, causing defects in unborn children.

Daniel Crawford of Virginia Tech's Department of Chemistry recently received a Cottrell Scholar Award for work he is doing in computational quantum chemistry. He is modeling molecules by computer, a process that can help determine the handedness of molecules that have been isolated from plants and animals and that have been found to have beneficial health effects. Therefore, when a drug is synthesized, it can be made to have the same handedness as the original molecule.

"If we look at a small molecule," Crawford said, "our models can be extremely accurate." However, he said, the methods do not scale well, so calculations on small molecules that take a few days may take years for larger ones.

Molecules with chirality, or handedness, such as amino acids, are common in natural-product research. Crawford is looking at the property of optical rotation as a way to identify the handedness of molecules. Different "hands" have different optical rotations. If polarized light is shone through a sample, the plane of the light will be rotated one way for one hand and the opposite way by the same number of degrees for the other hand. Crawford is working on computer models to compute that rotation accurately.

"At present, we don't have the ability to compute rotation with sufficient accuracy," Crawford said. When natural-products chemists isolate, from a plant or sea animal, for example, a new compound that has biological activity, they need to be able to determine the handedness of the molecules. "In such isolates, the molecules tend to be all of one hand," Crawford said, "but the natural-products chemists can't always tell which hand it is. All they know is what the optical rotation is."

However, when computational chemists carry out calculations, they always know what hand they have because they choose it, Crawford said. "We give the computer the structure," he said. "So if we can accurately compute the optical rotation of each hand of the molecule, then we need only to compare that to the rotation of the natural product to tell the experimentalist which hand they've got. They need to know so they can synthesize the correct one in the lab."

"If the natural product has one particular hand," Crawford said, "they must make analogs with the same hand." Otherwise, an effect like that of Thalidomide could occur.

Cottrell Scholar Awards, named in honor of the scientist, inventor, and philanthropist who founded Research Corporation in 1912 to provide means for scientific research and experimentation at scholarly institutions, contain two requirements: research and teaching. "There is a growing awareness that teaching and research are complementary rather than wholly or partially exclusive," according to the corporation.

Therefore, the awards go to faculty who "wish to excel at both teaching and research." Computational chemistry has a great impact on the field of chemistry as a whole; however, it is not heavily implemented in Virginia Tech's undergraduate curriculum, Crawford said. He therefore proposes to develop a series of laboratory experiments involving computational chemistry that would affect all undergraduate core chemistry courses--general, organic, physical, inorganic, and polymer. He has completed an experiment for general chemistry and will tackle organic chemistry this coming year.

Crawford's proposal was one of 12 funded out of 122 submitted in chemistry, physics, and astronomy from universities across the country. Crawford is the third faculty member in the Department of Chemistry--along with Brian Tissue and Paul Deck--to receive the Cottrell Scholar Award.

Crawford's research in theoretical and computational quantum chemistry already has earned him a National Science Foundation CAREER Award designed to encourage young researchers.