Journal of Molecular Modeling

, Volume 13, Issue 2, pp 291–296

Halogen bonding: the σ-hole

Proceedings of “Modeling interactions in biomolecules II”, Prague, September 5th–9th, 2005


    • Computer-Chemie-CentrumFriedrich-Alexander-Universität Erlangen-Nürnberg
  • Matthias Hennemann
    • Computer-Chemie-CentrumFriedrich-Alexander-Universität Erlangen-Nürnberg
  • Jane S. Murray
    • Department of ChemistryUniversity of New Orleans
  • Peter Politzer
    • Department of ChemistryUniversity of New Orleans
Original Paper

DOI: 10.1007/s00894-006-0130-2

Cite this article as:
Clark, T., Hennemann, M., Murray, J.S. et al. J Mol Model (2007) 13: 291. doi:10.1007/s00894-006-0130-2


Halogen 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.

Schematic 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.


Halogen bondingSigma-holeElectrostatic potentialDFT

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© Springer-Verlag 2006