A sigma-hole bond is a non-covalent interaction between a covalently-bonded atom of Groups III-VII (donor), bearing a region with a positive electrostatic potential (EP), and a negative site (acceptor). Nowadays, sigma-hole interactions have been found to occur in several organic and biological contexts [1]. The most common and well known sigma-hole bonds are halogen and chalcogen bonds, involving halogen and chalcogen atoms as electrophilic sites, respectively. In the last years, our groups have systematically investigated sigma-hole-dependent enantioseparations, showing that these interactions can actually work in HPLC environment, the occurrence of sigma-bonds being unreported therein [2a-d]. Moreover, envisaging for HPLC on chiral stationary phase (CSP) a novel function other than resolution of racemic mixture, we showed that HPLC and the CSP could be used as technical and molecular tools, respectively, for detection of stereoselective sigma-hole bonds and donors [2e]. On this basis, moving from HPLC towards biological contexts, iodinated 4,4'-bipyridines are currently under investigation as transthyretin (TTR) misfolding inhibitors. In this regard, halogen bonds are reported to underlie ligand-TTR binding, in some cases preventing protein misfolding which is involved in TTR amyloidosis diseases. In our studies, we used in parallel different computational approaches to gather complementary information on structures and recognition mechanisms by correlating experimental and theoretical data, particularly electrostatic potential surface analysis [3a], and molecular dynamics [2c-d,3b]. References [1] (a) Lange, A.; Gu?nther, M.; Bu?ttner, F. M.; Zimmermann, M. O.; Heidrich, J.; Hennig, S.; Zahn, S.; Schall, C.; Sievers-Engler, A.; Ansideri, F.; Koch, P.; Laemmerhofer, M.; Stehle, T.; Laufer, S. A.; Boeckler, F. M. J. Am. Chem. Soc. 2015, 137, 14640-14652; (b) Gilday, L. C. et al. Chem. Rev. 2015, 115, 7118-7195. [2] (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. et al. J. Chromatogr. A 2016, 1467, 228-238; (c) Dallocchio, R.; Dessì, A.; Solinas, M.; Arras, A.; Cossu, S.; Aubert, E.; Mamane, V.; Peluso, P. J. Chromatogr. A 2018, 1563, 71-81; (d) 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; (e) Peluso, P.; Mamane, V.; Dallocchio, R.; Dessì, A. et al. J. Sep. Sci. 2018, 41, 1247-1256. [3](a) Peluso, P.; Cossu, S. Chirality 2013, 25, 709-718; (b) Peluso, P.; Dessì, A.; Dallocchio, R.; Mamane, V.; Cossu, S. Electrophoresis 2019, DOI: 10.1002/elps.201800493

sigma-hole interactions in HPLC chiral recognition: a multidisciplinary approach towards new TTR misfolding inhibitors

P Peluso;R Dallocchio;G Andreotti;
2019

Abstract

A sigma-hole bond is a non-covalent interaction between a covalently-bonded atom of Groups III-VII (donor), bearing a region with a positive electrostatic potential (EP), and a negative site (acceptor). Nowadays, sigma-hole interactions have been found to occur in several organic and biological contexts [1]. The most common and well known sigma-hole bonds are halogen and chalcogen bonds, involving halogen and chalcogen atoms as electrophilic sites, respectively. In the last years, our groups have systematically investigated sigma-hole-dependent enantioseparations, showing that these interactions can actually work in HPLC environment, the occurrence of sigma-bonds being unreported therein [2a-d]. Moreover, envisaging for HPLC on chiral stationary phase (CSP) a novel function other than resolution of racemic mixture, we showed that HPLC and the CSP could be used as technical and molecular tools, respectively, for detection of stereoselective sigma-hole bonds and donors [2e]. On this basis, moving from HPLC towards biological contexts, iodinated 4,4'-bipyridines are currently under investigation as transthyretin (TTR) misfolding inhibitors. In this regard, halogen bonds are reported to underlie ligand-TTR binding, in some cases preventing protein misfolding which is involved in TTR amyloidosis diseases. In our studies, we used in parallel different computational approaches to gather complementary information on structures and recognition mechanisms by correlating experimental and theoretical data, particularly electrostatic potential surface analysis [3a], and molecular dynamics [2c-d,3b]. References [1] (a) Lange, A.; Gu?nther, M.; Bu?ttner, F. M.; Zimmermann, M. O.; Heidrich, J.; Hennig, S.; Zahn, S.; Schall, C.; Sievers-Engler, A.; Ansideri, F.; Koch, P.; Laemmerhofer, M.; Stehle, T.; Laufer, S. A.; Boeckler, F. M. J. Am. Chem. Soc. 2015, 137, 14640-14652; (b) Gilday, L. C. et al. Chem. Rev. 2015, 115, 7118-7195. [2] (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. et al. J. Chromatogr. A 2016, 1467, 228-238; (c) Dallocchio, R.; Dessì, A.; Solinas, M.; Arras, A.; Cossu, S.; Aubert, E.; Mamane, V.; Peluso, P. J. Chromatogr. A 2018, 1563, 71-81; (d) 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; (e) Peluso, P.; Mamane, V.; Dallocchio, R.; Dessì, A. et al. J. Sep. Sci. 2018, 41, 1247-1256. [3](a) Peluso, P.; Cossu, S. Chirality 2013, 25, 709-718; (b) Peluso, P.; Dessì, A.; Dallocchio, R.; Mamane, V.; Cossu, S. Electrophoresis 2019, DOI: 10.1002/elps.201800493
2019
Istituto di Chimica Biomolecolare - ICB - Sede Pozzuoli
Halogen bond
Bipyridine
Transthyretin
High-performance liquid chromatography
Enantioseparation
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.14243/390118
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