Skip to main content
SpringerLink
Log in

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

  • Original Paper
  • Published:
Journal of Molecular Modeling Aims and scope Submit manuscript

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.

Schematic models of halogen bonding complexes studied in this work

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12

Similar content being viewed by others

References

  1. Legon A (2010) Phys Chem Chem Phys 12:7736–7747

    Article  CAS  Google Scholar 

  2. Metrangolo P, Resnati G (2008) Halogen Bonding: Fundamentals and Applications Springer, Berlin

  3. Politzer P, Murray JS, Clark T (2010) Phys Chem Chem Phys 12:7748–7757

    Article  CAS  Google Scholar 

  4. Murray JS, Riley KE, Politzer P, Clark T (2010) Aust J Chem 63:1598–1607

    Article  CAS  Google Scholar 

  5. Metrangolo P, Neukirch H, Pilati T, Resnati G (2005) Acc Chem Res 38:386–395

    Article  CAS  Google Scholar 

  6. Metrangolo P, Resnati G, Pilati T, Liantonio R, Meyer F (2007) J Polym Sci 45:1–15

    CAS  Google Scholar 

  7. Voth AR, Ho PS (2007) Curr Top Med Chem 7:1336–1348

    Article  CAS  Google Scholar 

  8. Voth AR, Khuu P, Oishi K, Ho PS (2009) Nat Chem 1:74–79

    Article  CAS  Google Scholar 

  9. Lu YX, Shi T, Wang Y, Yang H, Yan X, Luo X, Jiang H, Zhu W (2009) J Med Chem 52:2854–2862

    Article  CAS  Google Scholar 

  10. Auffinger P, Hays FA, Westhof E, Ho PS (2004) Proc Nat Acad Sci USA 101:16789–16794

    Article  CAS  Google Scholar 

  11. Brinck T, Murray JS, Politzer P (1992) Int J Quant Chem Biol Symp 19:57–64

    Article  CAS  Google Scholar 

  12. Politzer P, Lane P, Concha MC, Ma YG, Murray JS (2007) J Mol Model 13:305–311

    Article  CAS  Google Scholar 

  13. Riley KE, Murray JS, Politzer P, Concha MC, Hobza P (2009) J Chem Theor Comput 5:155–163

    Article  CAS  Google Scholar 

  14. Shields Z, Murray JS, Politzer P (2010) Int J Quantum Chem 110:2823–2832

    Article  CAS  Google Scholar 

  15. Politzer P, Murray JS, Concha MC (2007) J Mol Model 13:643–650

    Article  CAS  Google Scholar 

  16. Clark T, Hennemann M, Murray JS, Politzer P (2007) J Mol Model 13:291–296

    Article  CAS  Google Scholar 

  17. Grabowski SJ, Bilewicz E (2006) Chem Phys Lett 427:51–55

    Article  CAS  Google Scholar 

  18. Lommerse JPM, Stone AJ, Taylor R, Allen FH (1996) J Am Chem Soc 118:3108–3116

    Article  CAS  Google Scholar 

  19. Nyburg SC, Wong-Ng W (1979) Proc R Soc Lond A 367:29–45

    Article  CAS  Google Scholar 

  20. Stevens ED (1979) Mol Phys 37:27–45

    Article  CAS  Google Scholar 

  21. Tsirelson VG, Zou PF, Tang TH, Bader RFW (1995) Acta Cryst A51:143–153

    CAS  Google Scholar 

  22. Price SL, Stone AJ, Lucas J, Rowland RS, Thornley AE (1994) J Am Chem Soc 116:4910–4918

    Article  CAS  Google Scholar 

  23. Riley KE, Hobza P (2008) J Chem Theor Comput 4:232–242

    Article  CAS  Google Scholar 

  24. Lu YX, Zou JW, Fan JC, Zhao WN, Jiang YJ, Yu QS (2009) J Comput Chem 30:725–732

    Article  CAS  Google Scholar 

  25. Kim CY, Chang JS, Doyon JB, Baird TT, Fierke CA, Jain A, Christianson DW (2000) J Am Chem Soc 122:12125–12134

    Article  CAS  Google Scholar 

  26. Kuhn B, Kollman PA (2000) J Am Chem Soc 122:3909–3916

    Article  CAS  Google Scholar 

  27. Raha K, van der Vaart AJ, Riley KE, Peters MB, Westerhoff LM, Kim H, Merz KM (2005) J Am Chem Soc 127:6583–6594

    Article  CAS  Google Scholar 

  28. Riley KE, Cui GL, Merz KM (2007) J Phys Chem B 111:5700–5707

    Article  CAS  Google Scholar 

  29. Boys SF, Bernardi F (1970) Mol Phys 19:553

    Article  CAS  Google Scholar 

  30. Werner HJ, Knowles PJ, Lindh R, Manby FR, Schütz M, Celani P, Korona T, Rauhut G, Amos RD, Bernhardsson A, Berning A, Cooper DL, Deegan MJO, Dobbyn AJ, Eckert F, Hampel C, Hetzer G, Lloyd AW, McNicholas SJ, Meyer W, Mura ME, Nicklaß A, Palmieri P, Pitzer P, Schumann U, Stoll H, Stone AJ, Tarroni R, Thorsteinsson, T (2008) MOLPRO (MOLPRO is a package of ab initio programs.)

  31. Politzer P, Truhlar DG (1981) Chemical Applications of Atomic and Molecular Electrostatic Potentials. Plenum, New York

    Google Scholar 

  32. Stewart RF (1979) Chem Phys Lett 65:335–342

    Article  CAS  Google Scholar 

  33. Murray JS, Politzer P (2011) The electrostatic potential: an overview. Wiley Interdisciplinary Reviews, in press

  34. Politzer P, Murray JS (2002) Theor Chem Acc 108:134–142

    Article  CAS  Google Scholar 

  35. Naray-Szabó G, Ferenczy GG (1995) Chem Rev 95:829–847

    Article  Google Scholar 

  36. Politzer P, Murray JS (1991) In: Lipkowitz KB, Boyd DB (eds) Reviews in Computational Chemistry Vol 2. VCH, New York

    Google Scholar 

  37. Bader RFW, Carroll MT, Cheeseman JR, Chang C (1987) J Am Chem Soc 109:7968–7979

    Article  CAS  Google Scholar 

  38. Bulat FA, Toro-Labbé A, Brinck T, Murray JS, Politzer P (2010) J Mol Model 16:1679–1691

    Article  CAS  Google Scholar 

  39. Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Chesseman JR, Zakrzewski VG, Montgomery Jr. JA, Stratmann RE, Burant JC, Dapprich S, Millam JM, Daniels AD, Kudin KN, Strain MC, Farkas O, Tomasi J, Barone V, Cossi M, Cammi R, Mennucci B, Pomelli C, Adamo C, Clifford S, Ochterski J, Petersson GA, Ayala PY, Cui Q, Morokuma K, Malick DK, Rabuck AD, Raghavachari K, Forseman JB, Cioslowski J, Ortiz JV, Baboul AG, Stefanov BB, Liu G, Liashenko A, Piskorz P, Komaromi I, Gomperts R, Martin RL, Fox DJ, Keith T, AlLoham MA, Peng CY, Nanayakkara A, Gonzalez C, Challacombe M, Gill PMW, Johnson BG, Chen W, Wong MW, Andres JL, Head-Gordon M, Replogle ES, Pople JA (2009) Guassian 09, Revision A.1. Gaussian Inc, Wallingford, CT

  40. Bondi A (1964) J Phys Chem 68:441–451

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors gratefully acknowledge the generous support of the National Science Foundation Experimental Program to Stimulate Competive Research Program (Grant number EPS-0701525) and the National Science Foundation Partnership for Research and Education in Materials Program (Grant number DMR-0934115). This work was a part of the research project No Z40550506 of the Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic , and it was supported by Grant No LC512 from the Ministry of Education, Youth and Sports of the Czech Republic.

Author information

Authors and Affiliations

  1. Department of Chemistry, University of Puerto Rico, Rio Piedras Campus, San Juan, Puerto Rico, 00931

    Kevin E. Riley, Ricardo J. Solá & Felix M. Ramos

  2. CleveTheoComp, 1951 W. 26th Street, Cleveland, OH, 44113, USA

    Jane S. Murray & Peter Politzer

  3. Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic and Center for Biomolecules and Complex Molecular Systems, 166 10, Prague 6, Czech Republic

    Jindřich Fanfrlík & Jan Řezáč

  4. Department of Chemistry, University of New Orleans, New Orleans, LA, 70148, USA

    Monica C. Concha

Authors
  1. Kevin E. Riley
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jane S. Murray
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jindřich Fanfrlík
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jan Řezáč
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ricardo J. Solá
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Monica C. Concha
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Felix M. Ramos
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Peter Politzer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kevin E. Riley.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Fig. S1

(DOC 114 kb)

Fig. S2

(DOC 86 kb)

Fig. S3

(DOC 86 kb)

Fig. S4

(DOC 85 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Riley, K.E., Murray, J.S., Fanfrlík, J. et al. Halogen bond tunability I: the effects of aromatic fluorine substitution on the strengths of halogen-bonding interactions involving chlorine, bromine, and iodine. J Mol Model 17, 3309–3318 (2011). https://doi.org/10.1007/s00894-011-1015-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00894-011-1015-6

Keywords

Search

Navigation