NEW METHODS FOR HPLC OPTICAL RESOLUTION AND DETECTION

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Differences between physiological properties and therapeutic effects of enantiomeric forms of many drugs have been recognized for sometime. Very often, an unwanted enantiomer can reverse or otherwise limit the effect of the desired enantiomer. Knowledge on the optical purity and ability to routinely perform the optical resolution of chiral substances are, therefore, of extreme importance to pharmacologists, biologists, biochemists as well as organic synthetic chemists, kineticists... Unfortunately, the currently available optical resolution methods can not be used for general chiral substances because they all suffer severe limitations and restrictions. The long term objective of the proposed research is to develop a novel method which is easy and fast but sensitive and effective for the general and routine determination of optical purity and separation of optical isomers. The developed method will be based on the high performance liquid chromatography technique (HPLC) because of its efficiency, speed and wide applicability. An innovative approach will be taken by incorporating critical phenomena into micellar technology to develop for, the first time, bile salt micellar solutions at critical temperature as chiral mobile phases. These novel chiral mobile phases are expected to provide higher resolution and efficiency and to widen the application of HPLC-optical resolution (HPLC-OR) to the general chiral substances. The advantages of laser, polarization and the photothermal effect will be taken to develop, for the first time, a laser photothermal refraction - circular dichroism spectropolarimeter (PR-CD) which is capable of determining the circular dichroism of small volume samples at very low concentrations. This PR-CD will then be used as fast, realtime and ultrasensitive circular dichroism detector for HPLC-CD.