$1 million NIH grant will help SU professors Nafie, Freedman develop new technique for analyzing chiral molecules

$1 million NIH grant will help SU professors Nafie, Freedman develop new technique for analyzing chiral moleculesApril 21, 2001Judy Holmesjlholmes@syr.edu

The National Institutes of Health has awarded a $1 million grant to Syracuse University Distinguished Professor Laurence Nafie and Tess Freedman, associate research professor in the Department of Chemistry in The College of Arts and Sciences, to develop a new method for analyzing molecules that could eventually become a valuable tool for the pharmaceutical industry. Nafie, nationally known for his research on chiral molecules, developed the first, commercially available tool that is used by drug companies and others to determine the molecular structure of chiral molecules using a new form of infrared spectroscopy. Chiral molecules–which include the primary molecules found in living organisms–exist as pairs that are nonsuperimposable mirror images. The pair of molecules interacts differently with chiral forms of infrared light in much the same way a left glove fits only on the left hand and only partly fits on the right hand. Similarly, the left- and right-hand molecules can behave in very different ways in the presence of other chiral molecules, Nafie says. For example, one form of a carvone molecule smells like spearmint, while its mirror image smells like caraway. The ability to determine which version of a chiral molecule is present in a substance is critical to the pharmaceutical industry. “In many cases, the mirror images of a chiral molecule can act like two different drugs,” Nafie says. “Generally, one form has a higher degree of potency than the other. But one form may also generate more side effects than the other.” 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, Nafie says. In other words, 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. Current techniques–VCD and X-ray–can be used on chiral molecules that can be dissolved in solution (VCD) or crystallized (X-ray). Prior to 1996, when Nafie’s Chiral Molecule Analyzer was marketed, X-ray crystallography was the only commercially available method to determine the molecular structure of chiral molecules. But not all molecules crystallize, which makes Nafie’s and Freedman’s VCD technique a valuable addition for the pharmaceutical industry. “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.