The origin of synthons and supramolecular motifs: beyond atoms and functional groups

This study establishes that hydrogen-, halogen- and chalcogen-bonding intermolecular and non-covalent intramolecular interactions are driven by a face-to-face orientation of electrophilic (charge-depleted) and nucleophilic (charge-concentrated) regions, which is the origin of the specific geometries found in synthons and supramolecular motifs.

A four-membered R₂²(4) supramolecular motif formed by S⋯S and S⋯I chalcogen-bonding interactions in the crystal structure of 4-iodo-1,3-di­thiol-2-one (C₃HIOS₂, IDT) is analysed and compared with a similar R₂²(4) motif (stabilized by Se⋯Se and Se⋯O chalcogen bonds) observed in the previously reported crystal structure of selena­phthalic anhydride (C₈H₄O₂Se, SePA) through detailed charge density analysis. Our investigation reveals that the chalcogen-bonding interactions participating in the R₂²(4) motifs observed in the two structures have the same characteristic orientation of local electrostatic electrophilic⋯nucleophilic interactions while involving different types of atoms. We carried out Cambridge Structural Database searches for synthons and supramolecular motifs involving chalcogen-, halogen- and hydrogen-bonding (ChB, XB and HB) interactions. Geometrical characterizations and topological analyses of the electron density ρ(r) and its negative Laplacian function [L(r) = −∇²ρ(r)] indicate that all the bonding interactions forming the motifs are driven by local electrophilic⋯nucleophilic interactions between complementary charge concentration (CC) and charge depletion (CD) sites present in the valence shells of the atoms, regardless of the atoms and functional groups involved. The graph-set assignment G_d^a(n) (G = C, R, D or S), formerly developed by Etter [Acc. Chem. Res. (1990), 23, 120–126] for HB interactions, is a convenient way to describe the connectivity in supramolecular motifs based on electrophilic⋯nucleophilic interactions (such as ChB, XB and HB interactions), exchanging the number of atomic acceptors (a) and donors (d) with the number of nucleophilic (n: CC) and electrophilic (e: CD) sites, and the number of atoms building the motif n by m, leading to the new graph-set assignment G_eⁿ(m) (G = C, R, D or S). Geometrical preferences in the molecular assembly of synthons and other supramolecular motifs are governed by the relative positions of CC and CD sites through CC⋯CD interactions that, in most cases, align with the internuclear directions within a <15° range despite low interaction energies. Accordingly, beyond atoms and functional groups, the origin of recurrent supramolecular structures embedded within different molecular environments is found in the local electrostatic complementarity of electrophilic and nucleophilic regions that are placed at particular geometries, driving the formation and the geometry of synthons and supramolecular motifs by directional and locally stabilizing electrostatic interactions.