Rapid Optical Purity Determination Using Chiral Spectroscopy, Achiral Spectroscopy, and Multivariate Analysis

A chemometric approach for determining enantiomeric purity from chirally sensitive spectral measurements such as circular dichroism (CD) in combination with conventional absorbance spectra has been demonstrated. This approach can be used to monitor process streams to ensure enantiomeric purity of chiral products without the need for chromatographic separation. The approach taken in this paper is a combination of the information available from conventional absorbance spectra, such as UV-Vis or IR, with that obtained by less prominent measurements which are sensitive to optical activity, such as circular dichroism or optical rotatory dispersion (ORD). By coupling these methods, one can obtain information about the concentrations of the desired components in a mixture as well as their enantiomeric purity. This information can be extracted from a number of optically active or optically inactive components simultaneously with the use of readily available multivariate analysis tools such as partial least-squares (PLS) or principal components regression (PCR), a feature unavailable with previously demonstrated single-wavelength measurements. This paper will focus on data from a set of test mixtures to evaluate the accuracy of predictions and to assess the best approach to predict the enantiomeric purities of the test mixtures. Three different mathematical approaches were used, and the results were compared to determine the best method for evaluating this type of data. In addition, the efficiency of this method for predicting enantiomer concentrations in complex mixtures was tested. Partial least-squares was shown to yield the most accurate prediction of the concentrations of even a complex mixture containing similar compounds with nearly indistinguishable spectral features.