Enantioseparation on chiral stationary phase (CSP) is based on the formation of transient diastereomeric selectand-selector complexes in a chiral environment generated by a chiral selector. Diverse short-range directional interactions, including hydrogen bonds, pai-pai, dipole-dipole, and van der Waals interactions, underlie complex formation and promote the enantioseparation [1]. In this context, recently, our groups discovered that sigma-hole interactions can be involved in HPLC enantioseparations, enlarging the range of interactions which are active in this environment [2]. Computational tools and studies in silico have greatly contributed to the understanding of sigma-hole interactions [3]. In particular, sigma-hole being a region of electronic charge depletion, electrostatic potentials (EPs) have been widely used as an indicator of the anisotropy of the molecular charge distribution. While it is well acknowledged that sigma-holes originate from the cylindrical symmetry of the sigma-bond and of the electron sharing along its axis, nothing is quantitatively known about the role played by the various moieties of a molecule in producing such holes. The Bader-Gatti source function [4] for the electron density (ED) was thus extended to the EP, to yield a rigorous measure of how the various pieces of a molecule determine the extent of sigma-holes as measured by the EP value at their associated EP maxima on the 0.002 au ED isosurface. A FORTRAN package was developed for such a purpose [2c]. A first application of the EPSF tool to the chalcogen bonds in HPLC enantioseparations of fluorinated 4,4'-bipyridines has been reported [2c]. Here, the EPSF method is presented in detail and new examples are discussed which concern halogenated and seleno-substituted atropisomeric 4,4'-bipyridines as sigma-hole bond donors. These compounds were enantioseparated on polysaccharide-based CSPs and used as test probes to study recognition mechanisms involving sigma-hole sites. References [1] Scriba, G. K. E., J. Chromatogr. A 2016, 1467, 56-78. [2] (a) Peluso, P., Mamane, V., Aubert, E., Dessì, A., Dallocchio, R., Dore, A., Pale, P., Cossu, S., J. Chromatogr. A 2016, 1467, 228-238; (b) Dallocchio, R., Dessì, A., Solinas, M., Arras, A., Cossu, S., Aubert, E., Mamane, V., Peluso, P., J. Chromatogr. A 2018, 1563, 71-81; c) 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. [3] Kolá?, M. H., Hobza, P., Chem. Rev. 2016, 116, 5155-5187. [4] Bader, R. F. W., Gatti, C., Chem. Phys. Lett. 1998, 287, 233-238. Acknowledgement: This work has been supported by Università Ca' Foscari Venezia, Italy (DSMN, ADIR funds). C. G. acknowledges funding from Danmarks Grundforskningsfond (award No. DNRF93).
The Electrostatic Potential Source Function (EPSF): a valuable tool to study enantioseparations involving sigma-holes as recognition sites
Paola Peluso;
2019
Abstract
Enantioseparation on chiral stationary phase (CSP) is based on the formation of transient diastereomeric selectand-selector complexes in a chiral environment generated by a chiral selector. Diverse short-range directional interactions, including hydrogen bonds, pai-pai, dipole-dipole, and van der Waals interactions, underlie complex formation and promote the enantioseparation [1]. In this context, recently, our groups discovered that sigma-hole interactions can be involved in HPLC enantioseparations, enlarging the range of interactions which are active in this environment [2]. Computational tools and studies in silico have greatly contributed to the understanding of sigma-hole interactions [3]. In particular, sigma-hole being a region of electronic charge depletion, electrostatic potentials (EPs) have been widely used as an indicator of the anisotropy of the molecular charge distribution. While it is well acknowledged that sigma-holes originate from the cylindrical symmetry of the sigma-bond and of the electron sharing along its axis, nothing is quantitatively known about the role played by the various moieties of a molecule in producing such holes. The Bader-Gatti source function [4] for the electron density (ED) was thus extended to the EP, to yield a rigorous measure of how the various pieces of a molecule determine the extent of sigma-holes as measured by the EP value at their associated EP maxima on the 0.002 au ED isosurface. A FORTRAN package was developed for such a purpose [2c]. A first application of the EPSF tool to the chalcogen bonds in HPLC enantioseparations of fluorinated 4,4'-bipyridines has been reported [2c]. Here, the EPSF method is presented in detail and new examples are discussed which concern halogenated and seleno-substituted atropisomeric 4,4'-bipyridines as sigma-hole bond donors. These compounds were enantioseparated on polysaccharide-based CSPs and used as test probes to study recognition mechanisms involving sigma-hole sites. References [1] Scriba, G. K. E., J. Chromatogr. A 2016, 1467, 56-78. [2] (a) Peluso, P., Mamane, V., Aubert, E., Dessì, A., Dallocchio, R., Dore, A., Pale, P., Cossu, S., J. Chromatogr. A 2016, 1467, 228-238; (b) Dallocchio, R., Dessì, A., Solinas, M., Arras, A., Cossu, S., Aubert, E., Mamane, V., Peluso, P., J. Chromatogr. A 2018, 1563, 71-81; c) 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. [3] Kolá?, M. H., Hobza, P., Chem. Rev. 2016, 116, 5155-5187. [4] Bader, R. F. W., Gatti, C., Chem. Phys. Lett. 1998, 287, 233-238. Acknowledgement: This work has been supported by Università Ca' Foscari 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.
