Courtesy of Professor Tess Freedman photo
Mirror image forms of a DNA fragment highlight one of the two strands in the double helix. The structure at right is the naturally occurring form.

Encounters With Vibrating Molecules
Distinguished Professor of Chemistry Laurence Nafie gets down to life’s basics when he studies the structure of molecules. But Nafie does more than examine molecules—he also builds highly specialized instruments that help scientists measure and analyze molecular structures. “I want to drive both the measurements and the calculations we use to very high levels of precision,” Nafie says. “In the lab, we want to push the boundaries of the frontier.”
     That’s nothing new for Nafie. As a molecular detective of sorts, he’s investigated the intriguing activities of life’s minuscule building blocks for more than three decades. In conversation, he talks about hitting molecules with infrared light, causing them to vibrate as they absorb the energy and leave unique signatures, or fingerprints, in the spectrum. He also talks about mapping the movements of swarming electrons and probing chiral (pronounced ky-ral) molecules, which exist in nature as pairs of non-superimposable mirror images of one another, like left and right hands. “Almost all of our interesting molecules—such as amino acids, proteins, and DNA—are chiral,” he says. “Life basically is characterized by the organization of chiral molecules. They’re very efficient; if you have two special molecules going together to do something, like a lock and key, the pairing won’t work if you have the wrong mirror image, and it will be rejected.”
      For the past 20 years, Nafie has collaborated with Tess Freedman, a chemistry research professor. Freedman is a specialist in the complex mathematical calculations and software programming that allow them to check theories against their experimental measurements. The researchers recently received a $1 million grant from the National Institutes of Health to develop even more sensitive molecular measurements and create a way to analyze molecules in solid form. (They’re currently dissolved into a solution prior to measurement.) This could lead to direct analyses of pharmaceutical drug tablets, ensuring that their molecular structures are accurate and safe, he says.
      Nafie, who just completed a 16-year stint as chair of the chemistry department, has been advancing the field of molecular spectroscopy since his days as a postdoctoral researcher at the University of Southern California in the early ’70s. He developed a spectrometer that led to his being the co-discoverer of a technique known as infrared vibrational circular dichroism (VCD). VCD spectroscopy exposes molecules to alternating patterns of left and right circularly polarized infrared light that travels in a helix-like or corkscrew pattern. In 1995, Nafie and Chicago researcher Rina Dukor launched the research company BioTools to promote VCD and develop a VCD spectrometer they had designed. Built by Quebec-based ABB Bomem Inc., the spectrometer, known as the Chiralir, transmits alternating beams of left and right circularly polarized infrared light at 1/37,000th-of-a-second intervals. For Nafie, the machine represents another step in his longtime professional pursuit of spreading the gospel about VCD spectroscopy. This is especially important for understanding chiral molecules because each vibrational mode in each molecule exhibits a preference for better absorbing either left or right circularly polarized light.
      Beyond the bounds of Earth, Nafie and a NASA scientist are exploring the possibility of building a miniaturized version of the Chiralir to put on NASA’s 2007 mission to Mars. Once there, the machine could be used to detect amino acids in soil samples and determine whether there’s any chirality. “If there’s chirality, then that’s a signature of life,” Nafie says. “It doesn’t prove life, but it’s strong evidence. The work we’re doing today is something I never thought I’d see in my lifetime.”


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