Halogen atoms (F, Cl, Br, I) involved in covalent bonds present anisotropic distribution of the electron density with a region of depleted and often positive electrostatic potential (EP) (the 'sigma-hole') on the elongation of the corresponding covalent bond [1]. On this basis, the halogen bond (XB) is defined as the attractive interaction between the positive?sigma-hole, which serves as a XB donor (XBD) and an electron-rich nucleophile site (XB acceptor) [2]. Recently, our groups have systematically investigated halogen-dependent enantioseparations using chiral polyhalogenated heterocycles as XBD probes on polysaccharide-based chiral stationary phases (PCSPs), demonstrating that XBs can actually drive enantioseparations [3]. In this context, with the aim of gaining information on the potential effect of regions of electronic charge depletion on retention and selectivity, here we report the results of further investigations performed by using 4,4'-bipyridyl, aryl and ferrocenyl halogenated derivatives as test probes on PCSPs. In our studies, we use in parallel four different computational approaches to gain complementary information on chiral recognition mechanisms by correlating experimental and theoretical data: a) EP surface analysis [4]; b) the Bader-Gatti electron density source function approach, suitably extended to the EP field, to evaluate the atomic contributions to local EP [5]; c) molecular dynamics simulations [3b-d,6]; d) time-dependent density functional theory calculations to obtain theoretical electronic circular dichroism spectra for absolute configuration assignment [3b,7]. References [1] Cavallo, G., Metrangolo, P., Milani, R., Pilati, T., Priimagi, A., Resnati, G., Terraneo, G., Chem. Rev. 2016, 116, 2478-2601. [2] Peluso, P., Mamane, V., Cossu, S., Chirality 2015, 27, 667-684. [3] a) Peluso, P., Mamane, V., Aubert, E., Cossu, S., J. Chromatogr. A 2014, 1345, 182-192; b) Peluso, P., Mamane, V., Aubert, E., Dessì, A., Dallocchio, R., Dore, A., Pale, P., Cossu, S., J. Chromatogr. A 2016, 1467, 228-238; c) 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; d) Dallocchio, R., Dessì, A., Solinas, M., Arras, A., Cossu, S., Aubert, E., Mamane, V., Peluso, P., J. Chromatogr. A 2018, 1563, 71-81. [4] Peluso, P., Cossu, S., Chirality 2013, 25, 709-718. [5] 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. [6] Peluso, P., Dessì, A., Dallocchio, R., Mamane, V., Cossu, S., Electrophoresis 2019, in press. [7] Mamane, V., Peluso, P., Aubert, E., Cossu, S., Pale, P., J. Org. Chem. 2016, 81, 4576-4587. 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).
Halogen bonds in HPLC enantioseparations: sigma-holes as recognition sites
Paola Peluso;
2019
Abstract
Halogen atoms (F, Cl, Br, I) involved in covalent bonds present anisotropic distribution of the electron density with a region of depleted and often positive electrostatic potential (EP) (the 'sigma-hole') on the elongation of the corresponding covalent bond [1]. On this basis, the halogen bond (XB) is defined as the attractive interaction between the positive?sigma-hole, which serves as a XB donor (XBD) and an electron-rich nucleophile site (XB acceptor) [2]. Recently, our groups have systematically investigated halogen-dependent enantioseparations using chiral polyhalogenated heterocycles as XBD probes on polysaccharide-based chiral stationary phases (PCSPs), demonstrating that XBs can actually drive enantioseparations [3]. In this context, with the aim of gaining information on the potential effect of regions of electronic charge depletion on retention and selectivity, here we report the results of further investigations performed by using 4,4'-bipyridyl, aryl and ferrocenyl halogenated derivatives as test probes on PCSPs. In our studies, we use in parallel four different computational approaches to gain complementary information on chiral recognition mechanisms by correlating experimental and theoretical data: a) EP surface analysis [4]; b) the Bader-Gatti electron density source function approach, suitably extended to the EP field, to evaluate the atomic contributions to local EP [5]; c) molecular dynamics simulations [3b-d,6]; d) time-dependent density functional theory calculations to obtain theoretical electronic circular dichroism spectra for absolute configuration assignment [3b,7]. References [1] Cavallo, G., Metrangolo, P., Milani, R., Pilati, T., Priimagi, A., Resnati, G., Terraneo, G., Chem. Rev. 2016, 116, 2478-2601. [2] Peluso, P., Mamane, V., Cossu, S., Chirality 2015, 27, 667-684. [3] a) Peluso, P., Mamane, V., Aubert, E., Cossu, S., J. Chromatogr. A 2014, 1345, 182-192; b) Peluso, P., Mamane, V., Aubert, E., Dessì, A., Dallocchio, R., Dore, A., Pale, P., Cossu, S., J. Chromatogr. A 2016, 1467, 228-238; c) 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; d) Dallocchio, R., Dessì, A., Solinas, M., Arras, A., Cossu, S., Aubert, E., Mamane, V., Peluso, P., J. Chromatogr. A 2018, 1563, 71-81. [4] Peluso, P., Cossu, S., Chirality 2013, 25, 709-718. [5] 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. [6] Peluso, P., Dessì, A., Dallocchio, R., Mamane, V., Cossu, S., Electrophoresis 2019, in press. [7] Mamane, V., Peluso, P., Aubert, E., Cossu, S., Pale, P., J. Org. Chem. 2016, 81, 4576-4587. 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.
