Halogen bonding: the σ-hole

AbstractHalogen bonding refers to the non-covalent interactions of halogen atoms X in some molecules, RX, with negative sites on others. It can be explained by the presence of a region of positive electrostatic potential, the σ-hole, on the outermost portion of the halogen’s surface, centered on the R–X axis. We have carried out a natural bond order B3LYP analysis of the molecules CF3X, with X = F, Cl, Br and I. It shows that the Cl, Br and I atoms in these molecules closely approximate the $$s^{2} p^{2}_{x} p^{2}_{y} p^{1}_{z} $$ configuration, where the z-axis is along the R–X bond. The three unshared pairs of electrons produce a belt of negative electrostatic potential around the central part of X, leaving the outermost region positive, the σ-hole. This is not found in the case of fluorine, for which the combination of its high electronegativity plus significant sp-hybridization causes an influx of electronic charge that neutralizes the σ-hole. These factors become progressively less important in proceeding to Cl, Br and I, and their effects are also counteracted by the presence of electron-withdrawing substituents in the remainder of the molecule. Thus a σ-hole is observed for the Cl in CF3Cl, but not in CH3Cl. FigureSchematic representation of the atomic charge generation. The molecular electrostatic potential (MEP) is calculated using the AM1* Hamiltonian. The semiempirical MEP is then scaled to DFT or ab initio level and atomic charges are generated from it by the restrained electrostatic potential (RESP) fit method.