Encoding Absolute Configurations with Chiral Enantiophore Descriptors. Application to the Order of Elution of Enantiomers in Liquid Chromatography

publication · 6 years ago
by Johann Gasteiger, Alberto Del Rio (Universität Erlangen-Nürnberg, Università di Modena e Reggio Emilia)

New chiral descriptors based on pharmacophore perception around the chiral center are used for the prediction of the orders of elution in chiral chromatography and are associated to the absolute configurations. This approach, in which the descriptors are based on the analysis of the strategic atoms around the stereogenic center, allows to describe the chirality of pharmacophore points in the ligand that are supposed to be important for the enantioselective recognition mechanism. ChirBase, a database for chiral chromatography, was used to extract 51 pairs of enantiomers separated on the commercially available Whelk-O1 chiral stationary phase. Modeling of the data with various techniques such as decision trees and artificial neural network were performed and high values of correct predictions were obtained with all modeling techniques, namely with more than 95% for training sets, about 85% for cross-validations, and about 80% for the external test set. The descriptors were used to collect precise and straightforward information about the mechanism of diastereomeric complexations as well as to elucidate the molecular requirements for obtaining a given elution order in a chiral separation. Since the descriptors completely denote the chirality of the enantiomers, the prediction of a new compound allows to unambiguously assign the absolute configurations to a given order of elution. This application opens new perspectives not only in the field of chiral High Performance Liquid Chromatography (HPLC) separations but also to boost the chemoinformatic research toward effective and relevant chiral descriptors derived from the pharmacophore perception that are likely to be important in many areas of chemistry and drug design.

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