REGIONS OF ELECTRONIC CHARGE DEPLETION AS RECOGNITION SITES IN HPLC ENANTIODISCRIMINATION

The enantioseparation of chiral compounds through the direct approach is an important matter in several fields of science [1]. This approach is based on the formation of transient diastereomeric selectand-selector complexes in a chiral environment generated by a chiral selector. Understanding the recognition pattern occurring in these processes remains a demanding issue in separation science because diverse short-range directional interactions, including hydrogen bonds, p-p, dipole-dipole, and van der Waals interactions, are able to promote the enantioseparation. Recently, sigma- and p-hole bonds involving atoms of Groups III-VII have also been considered as important directional noncovalent interactions [2], which involve regions of electronic charge depletion as recognition sites. The most common and well known sigma-hole bonds are halogen bonds (XB), involving halogen atoms and various Lewis bases. Besides XBs, sigma-hole interactions involving chalcogen atoms have also been identified, leading to the so-called chalcogen bonds (ChBs). Conceptually analogous to the sigma-hole bond, a p-hole bond is a noncovalent interaction which involves an unpopulated p* orbital (p-hole), as a donor, and a Lewis basis as acceptor (anion or lone-pair). A typical p-hole is located perpendicular to the molecular framework of perfluorinated aromatic rings. Computational tools and studies in silico have greatly contributed to the understanding of sigma- and p-hole based interactions. In particular, electrostatic potentials (EPs) have been widely used as an indicator of the anisotropy of the molecular charge distribution. Indeed, EP analysis allows to achieve detailed information of depth and size of electronic charge depletion and it can rationalize interaction preferences in competitive systems. On the other hand, computational techniques have been also used as tool in chiral chromatography to predict retention, selectivity and enantiomer elution order (EEO) with the aim to understand andrationalize recognition mechanisms. In this field, EPs and related EP surfaces (EPSs) contributed to investigate in detail the shape of both analyte and selector. Moreover, chromatography discrimination is a dynamic process based on reiterative adsorptiondesorption steps involving selector surface, cavities and groove. In this perspective, molecular dynamic (MD) simulations proved to be extremely versatile, in particular for studying processes where solvent effects have remarkable influence on driving interactions. Recently, our groups discovered that XBs can drive HPLC enantioseparations of halogenated analytes [3] by using cellulose tris(3,5-dimethylphenylcarbamate) (CDMPC) as a chiral selector (XB acceptor), enlarging the range of interactions which are active in HPLC environment [4,5]. Further to our recent results on the XB interactions, currently we are studying chalcogen and ?-hole bonds in HPLC environment. In particular, some unexplored issues concerning sigma- and p-hole driven enantioseparations have been addressed by using both MD simulations and EP analysis as computational tools [6]. Atomic contributions to the EPs maxima of sulphur in a series of chalcogen bond donors were derived using a molecular space partitioning in terms of Bader's atomic basins [7]. This procedure is akin to the Bader-Gatti electron density source function (SF) approach [8], suitably extended to the EP field [9].