Studies on new approaches of chiral discrimination for chiral analysis by regression modeling of spectral data.
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Modzabi, Selorm Kwame.
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Two new approaches of chiral discrimination for enantiomeric composition analysis using isotropic spectroscopic techniques and multivariate regression modeling were investigated. This is in view of the urgent need for rapid and improved strategies for chiral analysis due to the rising preference and demand for chiral drugs. In the first approach, (S)-(+)-1,2-propanediol or the racemic mixture of 2-butanol was reacted with the enantiomers of amino acids or chiral pharmaceutical compounds to form covalent derivatives (diastereomers). To circumvent usually long and cumbersome separation processes required by some chiral analysis techniques, the isotropic UV or fluorescence spectra of solutions of the reaction matrix containing the derivatized enantiomers were subjected to partial least squares regression (PLSR) modeling. PLSR was used as a means of extracting latent or structured information from the spectral data, which might contain interference and/or redundant information from the reaction matrix. Evaluation of the above approach using a test set of samples gave results with root-mean-square errors (RMSEs) of 0.0012-0.042. In the second approach, PLS-1 regression analysis were performed on the UV spectral data of samples containing different compositions of enantiomeric pairs, which were non-covalently discriminated in situ using a multi-functional chiral selected, (S)-(-)-1-phenylethylamine. Enantiomeric compositions of test samples of three amino acids and a carbohydrate determined using the second approach gave RMSEs of 0.006-0.025. In view of the need for micro-scale techniques in analyses such as this, a capillary tube, with a total volume of 95 µL, was custom-designed in the cause of this research for the measurement of fluorescence emission spectra of micro volumes of samples. The custom-designed capillary tube, which has an internal diameter of 1 mm and requires not more than 25 µL of sample solution for spectral measurement, was found to result in higher fluorescence emission intensities than measured using a commercial 10-mm pathlength fluorometer cell. Results of quantitative studies performed using the custom-designed capillary micro cell for spectral measurement were significantly identical to the results of studies conducted using the commercial cell.