The objective of this program is to develop an analytical instrument which will allow rapid determination of enantiomeric purity and/or molecular conformation. The determination of enantiomeric purity is important since the efficacy of some chiral drugs is diminished by the presence of the opposite enantiomer. The spectroscopic instrument will utilize the technique of Raman Optical Activity (ROA) for collection of enantiomeric information. The Phase I objective is to determine the analytical feasibility of a prototype ROA apparatus which can be utilized for biological, biochemical, pharmaceutical and clinical applications. Employment of a high throughput echelle spectrograph and charge coupled device (CCD) will enable collection of the entire Raman spectral range of interest at high resolution instantaneously. Efficient utilization of the traditional Raman spectrum as well as the ROA spectrum will enable the end user to determine molecular and enantiomeric information. In addition, state of the art micropositioners will make ROA less of a laboratory curiosity and more of an applications oriented technique. The potential utilization of near infrared (NIR) diode lasers enable the construction of a portable unit and would also minimize perturbation of enantiomeric conformation. The Phase II program would further develop the instrument, including the development of a probe for in situ analysis, and demonstrate the capabilities of the unit on several enantiomers and mixtures of enantiomers.
| Spencer, K M; Edmonds, R B; Rauh, R D et al. (1994) Analytical determination of enantiomeric purity using Raman optical activity. Anal Chem 66:1269-73 |
