In keeping with the importance of chirality in several fields, nowadays, high-performance liquid chromatography on chiral stationary phase (CSP) is largely used for resolving racemic mixtures of chiral compounds. In this field, polysaccharide-based CSPs (PCSPs) are the most versatile due to their polymeric structure where molecular, conformational and supramolecular chirality cooperate to determine the separation result.[1] The understanding of the chiral recognition mechanism is a basic requirement to design a successful enantioseparation. Nevertheless, this is still an unsolved problem for PCSPs because of the complexity of their structure, the presence of multiple active sites and the involvement of noncovalent interactions in the enantiorecognition process.[2] Currently, we are using in parallel four different computational approaches to gain complementary information on chiral recognition mechanisms by correlating experimental and theoretical data: a) electrostatic potential surface (EPS) analysis to investigate in detail the shape of both analyte and selector;[3] b) the Bader-Gatti electron density source function (SF) approach, suitably extended to the EP field, to evaluate the atomic contributions to local EP;[4] c) molecular dynamics to simulate the binding modes of the enantiomers with the polysaccharide-based selectors;[5] d) time-dependent density functional theory (TD-DFT) calculations to obtain theoretical electronic circular dichroism (ECD) spectra for absolute configuration assignment.[6] References [1] Chankvetadze, B., J. Chromatogr. A 2012, 1269, 26-51. [2] Lämmerhofer, M., J. Chromatogr. A 2010, 1217, 814-856. [3] Peluso, P., Cossu, S., Chirality 2013, 25, 709-718. [4] (a) Gatti, C., SF-ESI codes, 2018, Milano, Italy; (b) Peluso, P., Gatti, C., Dessì, A., Dallocchio, R., Weiss, R., Aubert, E., Pale, P., Cossu, S., Mamane, V., J. Chromatogr. A 2018, 1567, 119-129. [5] Peluso, P., Mamane, V., Dallocchio, R., Dessì, A., Villano, R., Sanna, D., Aubert, E., Pale, P., Cossu, S., J. Sep. Sci. 2018, 41, 1247-1256. [6] Mamane, V., Aubert, E., Peluso, P., Cossu, S., J. Org. Chem. 2012, 77, 2579-2583. Acknowledgement: This work has been supported by Università Ca' Foscari di Venezia, Italy (DSMN, ADIR funds). C. G. acknowledges funding from Danmarks Grundforskningsfond (award No. DNRF93).
Computational approaches for studying chiral recognition mechanisms in liquid chromatography environment
Paola Peluso;
2019-01-01
Abstract
In keeping with the importance of chirality in several fields, nowadays, high-performance liquid chromatography on chiral stationary phase (CSP) is largely used for resolving racemic mixtures of chiral compounds. In this field, polysaccharide-based CSPs (PCSPs) are the most versatile due to their polymeric structure where molecular, conformational and supramolecular chirality cooperate to determine the separation result.[1] The understanding of the chiral recognition mechanism is a basic requirement to design a successful enantioseparation. Nevertheless, this is still an unsolved problem for PCSPs because of the complexity of their structure, the presence of multiple active sites and the involvement of noncovalent interactions in the enantiorecognition process.[2] Currently, we are using in parallel four different computational approaches to gain complementary information on chiral recognition mechanisms by correlating experimental and theoretical data: a) electrostatic potential surface (EPS) analysis to investigate in detail the shape of both analyte and selector;[3] b) the Bader-Gatti electron density source function (SF) approach, suitably extended to the EP field, to evaluate the atomic contributions to local EP;[4] c) molecular dynamics to simulate the binding modes of the enantiomers with the polysaccharide-based selectors;[5] d) time-dependent density functional theory (TD-DFT) calculations to obtain theoretical electronic circular dichroism (ECD) spectra for absolute configuration assignment.[6] References [1] Chankvetadze, B., J. Chromatogr. A 2012, 1269, 26-51. [2] Lämmerhofer, M., J. Chromatogr. A 2010, 1217, 814-856. [3] Peluso, P., Cossu, S., Chirality 2013, 25, 709-718. [4] (a) Gatti, C., SF-ESI codes, 2018, Milano, Italy; (b) Peluso, P., Gatti, C., Dessì, A., Dallocchio, R., Weiss, R., Aubert, E., Pale, P., Cossu, S., Mamane, V., J. Chromatogr. A 2018, 1567, 119-129. [5] Peluso, P., Mamane, V., Dallocchio, R., Dessì, A., Villano, R., Sanna, D., Aubert, E., Pale, P., Cossu, S., J. Sep. Sci. 2018, 41, 1247-1256. [6] Mamane, V., Aubert, E., Peluso, P., Cossu, S., J. Org. Chem. 2012, 77, 2579-2583. Acknowledgement: This work has been supported by Università Ca' Foscari di Venezia, Italy (DSMN, ADIR funds). C. G. acknowledges funding from Danmarks Grundforskningsfond (award No. DNRF93).I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
