Author(s): Hagit Aviv, RN PhD, Bar-Ilan
Recently, developments in optical filters have enabled thefacile use of Raman spectroscopy to detect low-frequency vibrational (LFV) modes. We presented a new method for
differentiating racemic from enantiopure crystals by using, for the first time, Raman spectroscopy to characterize the LFV modes of crystalline organic materials composed of chiral molecules. The LF-Raman spectra of racemic and enantiopure crystals exhibit a significant variation, which we attribute to different hydrogen-bond networks in the chiral crystal structures. Across a representative set of amino acids, we observed that when comparing racemic versus enantiopure crystals, the available LFV modes
and their relative scattering intensity are strong functions of side chain polarity. Thus, LF-Raman can be used as a complementary method to the currently used methods
for characterizing crystal’s chirality. The pharmaceutical industry is in need of new techniques to identify the chirality of solids due to regulatory and safety concerns regarding
the biological activity of enantiomers. Since we found the LF-Raman spectra of racemic and enantiopure crystals are significantly different, we set out to demonstrate
the capabilities of our method for chiral purity investigation. For that we used a model system based on chiral crystals of enantiopure, racemic crystals and their mixtures in various ratios. Using this method, we were able to identify small amounts, as low as 1% w/w, of an enantiomer in racemic crystals. Comparing the achieved sensitivity for enantiomeric excess measurement in chiral crystals to that of circular dichroism and X-ray diffraction measurements showed that LF-Raman attains high sensitivity in solids that is similar to chiral optical methods used for solutions. Overall, our proposed approach of using Raman spectroscopy for determining enantiomeric excess in crystals is simple, faand offers a high degreeof chiral sensitivity.
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