predominates at long range, exchange becomes an important contribution around
the equilibrium position. Furthermore, the role of atomic destabilization was also
discussed, as well as that of secondary interactions, proving that the stabilization
energy of a halogen-bonded complex is the sum of competing effects, and does not
reduce to the interaction energy between the halogen atom and the nucleophilic
atom of the Lewis base. This is conversely the subtle combination of various factors
that make such interactions challenging and incentivizing for both experimentalists
and theoreticians.
Acknowledgements V.T. and L.J. gratefully acknowledge the CRIHAN computational centre for
providing computational resources, the Centre National de la Recherche Scientifique (CNRS) for a
“Chaire d’Excellence” at the University of Rouen, and the Labex SynOrg (ANR-11-LABX-0029).
References
1. Desiraju RG, Ho PS, Kloo L, Legon AC, Marquardt E, Metrangolo P, Politzer P, Resnati G,
Rissanen K (2013) Definition of the halogen bond (IUPAC recommendations 2013). Pure
Appl Chem 85:1711–1713
2. Metrangolo P, Pilati T, Resnati G (2006) Halogen bonding and other noncovalent
interactions involving halogens: a terminology issue. Cryst Eng Comm 8:946–947
3. Metrangolo P, Resnati G (eds) (2008) Halogen bonding: fundamentals and applications,
structure and bonding. Struct Bond 126. Springer, Berlin
4. Metrangolo P, Resnati G (2012) Halogen bonding: where we are and where we are going.
Cryst Growth Des 12:5835–5838
5. Legon AC (2010) The halogen bond: an interim perspective. Phys Chem Chem Phys
12:7736–7747
6. Fourmigué M (2009) Halogen bonding: recent advances. Curr Opin Solid State Mater Sci
13:36–45
7. Cavallo G, Metrangolo P, Pilati T, Resnati G, Terraneo G (2015) Halogen bond: a long
overlooked interaction. Top Curr Chem, Top Curr Chem 358:1–17
8. Scholfield MR, Zanden CM, Carter M, Ho PS (2013) Halogen bonding (X-bonding): a
biological perspective. Protein Sci 22:139–152
9. Lu Y, Wang Y, Zhu W (2010) Nonbonding interactions of organic halogens in biological
systems: implications for drug discovery and biomolecular design. Phys Chem Chem Phys
12:4543–4551
10. Auffinger P, Hays FA, Westhof E, Ho S (2004) Halogen bonds in biological molecules. Proc
Natl Acad Sci USA 101:16789–167945
11. Hardegger L-A, Kuhn B, Spinnler B, Anselm L, Ecabert R, Stihle M, Gsell B, Thoma R,
Diez J, Benz J, Plancher J-M, Hartmann G, Banner DW, Haap W, Diederich F (2011)
Systematic investigation of halogen bonding in protein-ligand interactions. Angew Chem Int
Ed 50:314–318
12. Jentzsch AV, Matile S (2013) Transmembrane halogen-bonding cascades. J Am Chem Soc
135:5302–5303
13. Wilcken R, Zimmermann MO, Lange A, Joerger AC, Boeckler FM (2013) Principles and
applications of halogen bonding in medicinal chemistry and chemical biology. J Med Chem
56:1363–1388
14. Parisini E, Metrangolo P, Pilati T, Resnati G, Terraneo G (2011) Halogen bonding in
halocarbon-protein complexes: a structural survey. Chem Soc Rev 40:2267–2278
454
V. Tognetti and L. Joubert
the equilibrium position. Furthermore, the role of atomic destabilization was also
discussed, as well as that of secondary interactions, proving that the stabilization
energy of a halogen-bonded complex is the sum of competing effects, and does not
reduce to the interaction energy between the halogen atom and the nucleophilic
atom of the Lewis base. This is conversely the subtle combination of various factors
that make such interactions challenging and incentivizing for both experimentalists
and theoreticians.
Acknowledgements V.T. and L.J. gratefully acknowledge the CRIHAN computational centre for
providing computational resources, the Centre National de la Recherche Scientifique (CNRS) for a
“Chaire d’Excellence” at the University of Rouen, and the Labex SynOrg (ANR-11-LABX-0029).
References
1. Desiraju RG, Ho PS, Kloo L, Legon AC, Marquardt E, Metrangolo P, Politzer P, Resnati G,
Rissanen K (2013) Definition of the halogen bond (IUPAC recommendations 2013). Pure
Appl Chem 85:1711–1713
2. Metrangolo P, Pilati T, Resnati G (2006) Halogen bonding and other noncovalent
interactions involving halogens: a terminology issue. Cryst Eng Comm 8:946–947
3. Metrangolo P, Resnati G (eds) (2008) Halogen bonding: fundamentals and applications,
structure and bonding. Struct Bond 126. Springer, Berlin
4. Metrangolo P, Resnati G (2012) Halogen bonding: where we are and where we are going.
Cryst Growth Des 12:5835–5838
5. Legon AC (2010) The halogen bond: an interim perspective. Phys Chem Chem Phys
12:7736–7747
6. Fourmigué M (2009) Halogen bonding: recent advances. Curr Opin Solid State Mater Sci
13:36–45
7. Cavallo G, Metrangolo P, Pilati T, Resnati G, Terraneo G (2015) Halogen bond: a long
overlooked interaction. Top Curr Chem, Top Curr Chem 358:1–17
8. Scholfield MR, Zanden CM, Carter M, Ho PS (2013) Halogen bonding (X-bonding): a
biological perspective. Protein Sci 22:139–152
9. Lu Y, Wang Y, Zhu W (2010) Nonbonding interactions of organic halogens in biological
systems: implications for drug discovery and biomolecular design. Phys Chem Chem Phys
12:4543–4551
10. Auffinger P, Hays FA, Westhof E, Ho S (2004) Halogen bonds in biological molecules. Proc
Natl Acad Sci USA 101:16789–167945
11. Hardegger L-A, Kuhn B, Spinnler B, Anselm L, Ecabert R, Stihle M, Gsell B, Thoma R,
Diez J, Benz J, Plancher J-M, Hartmann G, Banner DW, Haap W, Diederich F (2011)
Systematic investigation of halogen bonding in protein-ligand interactions. Angew Chem Int
Ed 50:314–318
12. Jentzsch AV, Matile S (2013) Transmembrane halogen-bonding cascades. J Am Chem Soc
135:5302–5303
13. Wilcken R, Zimmermann MO, Lange A, Joerger AC, Boeckler FM (2013) Principles and
applications of halogen bonding in medicinal chemistry and chemical biology. J Med Chem
56:1363–1388
14. Parisini E, Metrangolo P, Pilati T, Resnati G, Terraneo G (2011) Halogen bonding in
halocarbon-protein complexes: a structural survey. Chem Soc Rev 40:2267–2278
454
V. Tognetti and L. Joubert