Journal of Molecular Modeling

, Volume 17, Issue 12, pp 3309–3318

Halogen bond tunability I: the effects of aromatic fluorine substitution on the strengths of halogen-bonding interactions involving chlorine, bromine, and iodine

  • Kevin E. Riley
  • Jane S. Murray
  • Jindřich Fanfrlík
  • Jan Řezáč
  • Ricardo J. Solá
  • Monica C. Concha
  • Felix M. Ramos
  • Peter Politzer
Original Paper

DOI: 10.1007/s00894-011-1015-6

Cite this article as:
Riley, K.E., Murray, J.S., Fanfrlík, J. et al. J Mol Model (2011) 17: 3309. doi:10.1007/s00894-011-1015-6

Abstract

In the past several years, halogen bonds have been shown to be relevant in crystal engineering and biomedical applications. One of the reasons for the utility of these types of noncovalent interactions in the development of, for example, pharmaceutical ligands is that their strengths and geometric properties are very tunable. That is, substitution of atoms or chemical groups in the vicinity of a halogen can have a very strong effect on the strength of the halogen bond. In this study we investigate halogen-bonding interactions involving aromatically-bound halogens (Cl, Br, and I) and a carbonyl oxygen. The properties of these halogen bonds are modulated by substitution of aromatic hydrogens with fluorines, which are very electronegative. It is found that these types of substitutions have dramatic effects on the strengths of the halogen bonds, leading to interactions that can be up to 100% stronger. Very good correlations are obtained between the interaction energies and the magnitudes of the positive electrostatic potentials (σ-holes) on the halogens. Interestingly, it is seen that the substitution of fluorines in systems containing smaller halogens results in electrostatic potentials resembling those of systems with larger halogens, with correspondingly stronger interaction energies. It is also shown that aromatic fluorine substitutions affect the optimal geometries of the halogen-bonded complexes, often as the result of secondary interactions.

https://static-content.springer.com/image/art%3A10.1007%2Fs00894-011-1015-6/MediaObjects/894_2011_1015_Figa_HTML.gif
Figure

Schematic models of halogen bonding complexes studied in this work

Keywords

BromobenzenesChlorobenzenesElectrostatic potentialsFluorine substitutionHalogen bondingIodobenzenesTunability

Supplementary material

894_2011_1015_MOESM1_ESM.doc (114 kb)
Fig. S1(DOC 114 kb)
894_2011_1015_MOESM2_ESM.doc (86 kb)
Fig. S2(DOC 86 kb)
894_2011_1015_MOESM3_ESM.doc (86 kb)
Fig. S3(DOC 86 kb)
894_2011_1015_MOESM4_ESM.doc (86 kb)
Fig. S4(DOC 85 kb)

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Kevin E. Riley
    • 1
  • Jane S. Murray
    • 2
  • Jindřich Fanfrlík
    • 3
  • Jan Řezáč
    • 3
  • Ricardo J. Solá
    • 1
  • Monica C. Concha
    • 4
  • Felix M. Ramos
    • 1
  • Peter Politzer
    • 2
  1. 1.Department of ChemistryUniversity of Puerto RicoSan JuanPuerto Rico
  2. 2.CleveTheoCompClevelandUSA
  3. 3.Institute of Organic Chemistry and BiochemistryAcademy of Sciences of the Czech Republic and Center for Biomolecules and Complex Molecular SystemsPrague 6Czech Republic
  4. 4.Department of ChemistryUniversity of New OrleansNew OrleansUSA