Research project to help pharmaceutical industry examine molecular structure of pills

Two Syracuse University researchers are conducting research to develop a new tool for the pharmaceutical industry that will more closely examine the molecular structure of pills. Such a tool will help pharmaceutical companies develop more effective medications that are safer and more beneficial to the millions of people who take pills every day.

Supported with a $1 million grant from the National Institutes of Health, Syracuse University Distinguished Professor Laurence Nafie and Tess Freedman, associate research professor in the Department of Chemistry, are looking to improve similar tools developed earlier by the two researchers. Nafie, nationally known for his research on chiral molecules, developed the first, commercially available tool used by drug researchers. Nafie, nationally known for his research on chiral molecules, developed the first, commercially available tool used by drug companies to determine the molecular structure of chiral molecules using a form of infrared spectroscopy.

Chiral molecules--which include the primary molecules found in living organisms--exist as pairs that are nonsuperimposable mirror images. In many cases, the mirror images of a chiral molecule can act like two different drugs. Generally, one form has a higher degree of potency than the other, and one form may also generate more side effects than the other. The ability to determine which version of a chiral molecule is present in a substance is critical to the pharmaceutical industry.

A classic example that had tragic results was thalidomide, a drug developed during the early 1960s to treat morning sickness in pregnant women. In that case, one form of the chiral molecule had the intended effect, Nafie says. However, one side effect of the mirror image was severe birth defects.

Nafie and Freedman developed a technique, called vibrational circular dichroism (VCD), that enables scientists to determine the left- and right-hand structures of chiral molecules using infrared spectroscopy.

Their tool, called a Chiral Molecule Analyzer, is now being manufactured by ABB Bomem Inc. in Quebec and is used by pharmaceutical companies. The NIH grant will extend their research into the near-infrared area; the researchers will try to develop a technique that uses near-infrared spectroscopy to determine the molecular structure of chiral molecules. Near-infrared vibrational circular dichroism spectroscopy, an area in which there has been little research, would also enable scientists to analyze chiral molecules in a solid form.

"Near-infrared VCD spectroscopy would enable us to look at the whole pill and find out if it has the amount of right- and left-handed molecules that we think it has," Freedman says. "It would also enable us to detect the interactions between the active ingredient, the stabilizers and the fillers that make up the whole pill."

And it could save valuable research time for the pharmaceutical industry, Nafie says. During the 1990s, the technology became available to make chirally pure drugs that contain only one form of the molecule. If a drug company wants to sell a chirally mixed drug, the federal Food and Drug Administration requires that the company separately test the left- and right-handed versions of the molecule, and run a third test on a mixture of the two.

"If we could bring chiral sensitivity to the near infrared range, it could help the industry improve quality control over its products," Nafie says.