Chiral Purity of Crystals Using Low‐Frequency Raman Spectroscopy. Issue 22 (4th October 2018)

• Record Type: Journal Article
• Authors: Nemtsov, Irena; Mastai, Yitzhak; Tischler, Yaakov R.; Aviv, Hagit
• Is Part Of: Chemphyschem. Volume 19:Issue 22(2018)
• Page Start: 3116
• Page End: 3121
• Publication Date: 2018-10-04
• Subjects: Chirality -- enantiomers -- low-frequency Raman spectroscopy -- racemates -- X-ray diffraction; Chemistry, Physical and theoretical -- Periodicals; 541.05
• DOI: 10.1002/cphc.201800739
• Languages: English
• ISSNs: 1439-4235

Abstract

Abstract: 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. In this study, we present for the first time the application of low‐frequency Raman spectroscopy as a new and sensitive method for analyzing the chiral purity of crystals. Using this method, we were able to identify small amounts, as low as 1 % w/w, of an enantiomer in racemic crystals. To demonstrate the capabilities of the method, we used a model system based on chiral crystals of enantiopure, racemic crystals and their mixtures in various ratios. We found that the low‐frequency Raman spectra of racemic and enantiopure crystals are significantly different, reflecting the different hydrogen bond networks. Moreover, a comparison of the sensitivity of enantiomeric excess in chiral crystals to that of circular dichroism and X‐ray diffraction measurements showed that low‐frequency Raman attains high sensitivity comparable to chiral optical methods used for solutions. Overall, our proposed approach of using Raman spectroscopy for determining enantiomeric excess in crystals is simple, fast, and offers a high degree of chiral sensitivity. Abstract : Crystal clear : Low‐frequency Raman spectroscopy is employed to investigate chiral purity in crystals. In the left part of the image, a measured chiral crystal powder of tartaric acid (containing enantiomeric excess) is in the focal volume. A comparison of the output spectra (top right) with the spectra of pure racemic and the enantiomer crystal of tartaric acid (bottom right) provides evidence of enantiomer contamination within the racemic crystal.