NIST DEVELOPING OPTICAL TECHNOLOGIES FOR ASSESSING STRUCTURES OF CHIRAL MOLECULES.

Many organic compounds exist in two identical chemical structures that are mirror images of each other--a characteristic called chirality. In particular, a number of pharmaceuticals are chiral, and while one "enantiomer" may have beneficial effects, the other may be inactive or even produce undesirable effects. Concern over possible or demonstrated negative side effects from one of the enantiomers has accelerated the effort to market single enantiomer or chiral pure drugs.

Despite the demonstrated importance of chiral drugs, the detailed physics underlying the biomolecular interactions responsible for their enantiomeric selectivity often remain obscure. Of fundamental importance is the ability to determine the three-dimensional structure of chiral molecules, and an often-used technique for structural characterization has been to investigate the optical activ-ity of chiral molecules. However, the quantum mechanical models that relate these measurements to molecular structure have not been rigorously tested.

Recently, NIST researchers have successfully characterized the molecular structure of the chiral prototype, binapthol, using high-resolution microwave and ultraviolet molecular-beam spectroscopies. The structure and electronic spectrum of binapthol are being investigated to provide quantitative data to test theories relating optical activity to molecular structure. The researchers recently modified the technique of cavity ringdown spectroscopy to allow sensitive ultraviolet optical-activity measurements. The combination of these spectroscopic techniques will provide a rigorous and unprecedented test of current theories that relate optical activity to molecular structure and, in turn, assist efforts toward understanding the biophysics underlying physiological chiral selectivity.