Virtual chiral recognition of eugenol derivatives on amylose tris(3-chloro-5-methylphenylcarbamate) chiral stationary phase in unusual normal-phase mode

Gaia Pulitelli; Francesca Romana Mammone; Daniele Sadutto; Damiano Tanini; Roberto Cirilli

doi:10.1016/j.aca.2023.341811

Virtual chiral recognition of eugenol derivatives on amylose tris(3-chloro-5-methylphenylcarbamate) chiral stationary phase in unusual normal-phase mode

Anal Chim Acta. 2023 Oct 23:1279:341811. doi: 10.1016/j.aca.2023.341811. Epub 2023 Sep 11.

Authors

Gaia Pulitelli¹, Francesca Romana Mammone¹, Daniele Sadutto¹, Damiano Tanini², Roberto Cirilli³

Affiliations

¹ Centre for the Control and Evaluation of Medicines, Chemical Medicines Unit, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy.
² Department of Chemistry "Ugo Schiff", University of Florence, Via Della Lastruccia 3-13, I-50019, Sesto Fiorentino, Italy.
³ Centre for the Control and Evaluation of Medicines, Chemical Medicines Unit, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy. Electronic address: roberto.cirilli@iss.it.

PMID: 37827619
DOI: 10.1016/j.aca.2023.341811

Abstract

Chromatographic enantioseparation on polysaccharide-based chiral stationary phases has undergone explosive development over the last three decades as a method for separating the enantiomers of chiral compounds on an analytical and preparative scale. In this context, understanding the nature of the intermolecular interactions involved in retention and recognition processes is an interesting scientific challenge. In the present study, three eugenol derivatives were used as chiral references to elucidate some unexplored aspects of the enantioselective and retention properties of the Chiralpak IG-U chiral stationary phase based on amylose-tris(3-chloro-5-methylphenylcarbamate). The performance of the ultra-high performance liquid chromatography chiral packing material Chiralpak IG-U was evaluated using a two-step approach. First, binary mixtures containing variable proportions of alcohol (ethanol or 2-propanol) in n-hexane were used as mobile phases and the retention factors were recorded at three different temperatures. A rational analysis of this set of chromatographic data shows the leading role played by hydrogen bond between the OH group linked to the stereogenic centre of the analytes and the active sites of the chiral chromatographic material in obtaining a high degree of enantioseparation. The retention factors were then plotted against the percentage of alcohol modifiers to obtain retention maps with a non-linear performance trend with correlation factors >0.9990. The proposed retention map model was used to extrapolate and describe virtual chiral recognition of chiral analytes on the Chiralpak IG-U chiral stationary phase under extreme elution conditions with expected run times of hundreds or thousands of years. The presented virtual chiral recognition approach is based on a generic concept and therefore opens new possibilities for understanding the performance of other polysaccharide-based chiral stationary phases.

Keywords: Chiralpak IG-U; Hydrogen bond; Retention maps; Retention prediction; Virtual chiral recognition.