sigma- AND pai-HOLE BONDS IN ENANTIOSEPARATION SCIENCE

A sigma-hole bond is a noncovalent interaction (R-Donor···Acceptor) between a covalently-bonded atom of Groups 13-18, bearing an electrophilic region for electron charge density depletion, and a negative site such as anion, lone electron pair, pai- electrons. Among these interactions, halogen and chalcogen bonds (HaB and ChB) have been the most studied so far. The pai-hole bond also is a noncovalent interaction related to regions of electronic charge density depletion involving a pai-electronic cloud in general centred on fluorinated aromatic rings [1]. In the last decades, these noncovalent interactions have found practical application in several fields. In separation science, despite the pivotal role of noncovalent interactions in this field, investigations of sigma-hole bonds are still in their infancy, and so far, just a limited number of studies focusing on HaB and sigma-hole functions in solid phase extraction, liquid-liquid microextraction, liquid-phase chromatography, and gas chromatography separation have been published. In enantioseparation science, the first observations can be traced back to 1996, when Pirkle's group highlighted an unexpected halogen effect on the enantioseparation of chiral compounds [2]. Nevertheless, in these studies, halogen-dependent effects on enantioseparation were never explicitly related to the HaB. In the last decade, our groups have been systematically studying the potentiality of sigma- and pai-hole bonds for HPLC enantioseparations, demonstrating that these interactions can actually participate in enantiorecognition mechanisms [3,4]. In this lecture, up-to-date results emerging from focused experiments and theoretical analyses performed by our laboratories will be integrated with a descriptive presentation of sigma- and pai-hole bond features and the few studies published until now in separation science. A critical discussion of the topic will be provided, accounting for some still open issues in the application of sigma- and pai-hole bonds to separate chemical (chiral) mixtures. [1]P. Politzer, J. S. Murray. An overview of strengths and directionalities of noncovalent interactions: ?-holes and ?-holes. Crystals 9 (2019) 165. [2]W. H. Pirkle, K. Z. Gan, L. J. Brice. The enhancement of enantioselectivity by halogen substituents. Tetrahedron Asymmetry 7 (1996) 2813-2816. [3]P. Peluso, V. Mamane et al. Halogen bond in separation science: a critical analysis across experimental and theoretical results. J. Chromatogr. A 1616 (2020) 460788. [4]P. Peluso, A. Dessì et al. Enantioseparation of 5,5'-dibromo-2,2'-dichloro-3-selanyl-4,4'-bipyridines on polysaccharide-based chiral stationary phases: exploring chalcogen bonds in liquid-phase chromatography. Molecules 26 (2021) 221.