Journal of Molecular Modeling

, Volume 13, Issue 2, pp 291–296 | Cite as

Halogen bonding: the σ-hole

Proceedings of “Modeling interactions in biomolecules II”, Prague, September 5th–9th, 2005
  • Timothy ClarkEmail author
  • Matthias Hennemann
  • Jane S. Murray
  • Peter Politzer
Original Paper


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 bonding Sigma-hole Electrostatic potential DFT 


  1. 1.
    Dumas J-M, Peurichard H, Gomel M (1978) J Chem Res Synop 54–55Google Scholar
  2. 2.
    Dumas J-M, Geron C, Peurichard H, Gomel M (1976) Bull Soc Chim France 720–728Google Scholar
  3. 3.
    Dumas J-M, Kern M, Janier-Dubry JL (1976) Bull Soc Chim France 1785–1790Google Scholar
  4. 4.
    Murray-Rust P, Motherwell WDS (1979) J Am Chem Soc 101:4374–4376CrossRefGoogle Scholar
  5. 5.
    Murray-Rust P, Stallings WC, Monti CT, Preston RK, Glusker JP (1983) J Am Chem Soc 105:3206–3214CrossRefGoogle Scholar
  6. 6.
    Ramasubbu N, Parthasarathy R, Murray-Rust P (1986) J Am Chem Soc 108:4308–4314CrossRefGoogle Scholar
  7. 7.
    Bent HA (1968) Chem Rev 68:587–648CrossRefGoogle Scholar
  8. 8.
    Hassel O (1970) Science 170:497–502CrossRefGoogle Scholar
  9. 9.
    Bernard-Houplain M-C, Sandorfy C (1973) Can J Chem 51:1075–1082CrossRefGoogle Scholar
  10. 10.
    Bernard-Houplain M-C, Sandorfy C (1973) Can J Chem 51:3640–3646CrossRefGoogle Scholar
  11. 11.
    Di Paolo T, Sandorfy (1974) Chem Phys Lett 26:466–469CrossRefGoogle Scholar
  12. 12.
    Di Paolo T, Sandorfy C (1974) Can J Chem 52:3612–3622CrossRefGoogle Scholar
  13. 13.
    Auffinger P, Hays FA, Westhof E, Shing Ho P (2004) Proc Nat Acad Sci 101:16789–16794CrossRefGoogle Scholar
  14. 14.
    Metrangolo P, Neukirch H, Pilati T, Resnati G (2005) Acc Chem Res 38:386–395CrossRefGoogle Scholar
  15. 15.
    Brinck T, Murray JS, Politzer P (1992) Int J Quantum Chem, Quantum Biol Symp 19:57–64CrossRefGoogle Scholar
  16. 16.
    Murray JS, Paulsen K, Politzer P (1994) Proc Indian Acad Sci (Chem Sci) 106:267–275Google Scholar
  17. 17.
    Politzer P, Lane P, Concha MC, Ma Y, Murray JS (2006) J Mol Model DOI 10.1007/s00894-006-0154-7 (this issue)
  18. 18.
    Stewart RF (1972) J Chem Phys 57:1664–1668CrossRefGoogle Scholar
  19. 19.
    Naray-Szabo G, Ferenczy GG (1995) Chem Rev 95:829–847CrossRefGoogle Scholar
  20. 20.
    Bader RFW, Carroll MT, Cheeseman JR, Chang C (1987) J Am Chem Soc 109:7968–7979CrossRefGoogle Scholar
  21. 21.
    Weinstein H, Politzer P, Srebrenik S (1975) Theor Chim Acta 38:159–163CrossRefGoogle Scholar
  22. 22.
    Politzer P, Murray JS (2002) Theor Chem Accts 108:134–142Google Scholar
  23. 23.
    Flükiger PF (1992) Development of the molecular graphics package MOLEKEL and its application to selected problems in organic and organometallic chemistry. Thèse No. 2561. Département de chimie physique, Université de Genève, GenèveGoogle Scholar
  24. 24.
    Portmann S, Lüthi HP (2000) CHIMIA 54:766–770; Google Scholar
  25. 25.
    Lommerse JPM, Stone AJ, Taylor R, Allen FH (1996) J Am Chem Soc 118:3108–3116CrossRefGoogle Scholar
  26. 26.
    Valerio G, Raos G, Meille SV, Metrangolo P, Resnati G (2000) J Phys Chem A 104:1617–1620CrossRefGoogle Scholar
  27. 27.
    Romaniello P, Lelj F (2002) J Phys Chem A 106:9114–9119CrossRefGoogle Scholar
  28. 28.
    Reed AE, Curtiss LA, Weinhold F (1988) Chem Rev 88:899–926CrossRefGoogle Scholar
  29. 29.
    Becke AD (1993) J Chem Phys 98:5648–5652CrossRefGoogle Scholar
  30. 30.
    Lee C, Yang W, Parr RG (1988) Phys Rev B 37:785–789CrossRefGoogle Scholar
  31. 31.
    Ditchfield R, Hehre WJ, Pople JA (1971) J Chem Phys 54:724–728CrossRefGoogle Scholar
  32. 32.
    Hehre WJ, Ditchfield R, Pople JA (1972) J Chem Phys 56:2257–2261CrossRefGoogle Scholar
  33. 33.
    Hariharan PC, Pople JA (1974) Mol Phys 27:209–214CrossRefGoogle Scholar
  34. 34.
    Gordon MS (1980) Chem Phys Lett 76:163–168CrossRefGoogle Scholar
  35. 35.
    Hariharan PC, Pople JA (1973) Theo Chim Acta 28:213–222CrossRefGoogle Scholar
  36. 36.
    Blaudeau J-P, McGrath MP, Curtiss LA, Radom L (1997) J Chem Phys 107:5016–5021CrossRefGoogle Scholar
  37. 37.
    Francl MM, Pietro WJ, Hehre WJ, Binkley JS, DeFrees DJ, Pople JA, Gordon MS (1982) J Chem Phys 77:3654–3665CrossRefGoogle Scholar
  38. 38.
    Binning RC Jr, Curtiss LA (1990) J Comp Chem 11:1206–1216CrossRefGoogle Scholar
  39. 39.
    Rassolov VA, Pople JA, Ratner MA, Windus TL (1998) J Chem Phys 109:1223–1229CrossRefGoogle Scholar
  40. 40.
    Rassolov A, Ratner MA, Pople JA, Redfern PC, Curtiss LA (2001) J Comp Chem 22:976–984CrossRefGoogle Scholar
  41. 41.
    Clark T, Chandrasekhar J, Spitznagel GW, Schleyer PvR (1983) J Comp Chem 4:294–301CrossRefGoogle Scholar
  42. 42.
    Godbout N, Salahub DR, Andzelm J, Wimmer E (1992) Can J Chem 70:560–571CrossRefGoogle Scholar
  43. 43.
    Sosa C, Andzelm J, Elkin BC, Wimmer E, Dobbs KD, Dixon DA (1992) J Phys Chem 96:6630–6636CrossRefGoogle Scholar
  44. 44.
    Kutzelnigg W (1984) Angew Chem 96:262–286Google Scholar
  45. 45.
    Kutzelnigg W (1984) Angew Chem Int Ed Engl 23:272–295CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Timothy Clark
    • 1
    Email author
  • Matthias Hennemann
    • 1
  • Jane S. Murray
    • 2
  • Peter Politzer
    • 2
  1. 1.Computer-Chemie-CentrumFriedrich-Alexander-Universität Erlangen-NürnbergErlangenGermany
  2. 2.Department of ChemistryUniversity of New OrleansNew OrleansUSA

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