Abstract

The importance of halogen bonds—highly directional interactions between an electron-deficient σ-hole moiety in a halogenated compound and an acceptor such as a Lewis base—is being increasingly recognized in a wide variety of fields from biomedicinal chemistry to materials science. The heaviest halogens are known to form stronger halogen bonds, implying that if this trend continues down the periodic table, astatine should exhibit the highest halogen-bond donating ability. This may be mitigated, however, by the relativistic effects undergone by heavy elements, as illustrated by the metallic character of astatine. Here, the occurrence of halogen-bonding interactions involving astatine is experimentally evidenced. The complexation constants of astatine monoiodide with a series of organic ligands in cyclohexane solution were derived from distribution coefficient measurements and supported by relativistic quantum mechanical calculations. Taken together, the results show that astatine indeed behaves as a halogen-bond donor—a stronger one than iodine—owing to its much more electrophilic σ-hole.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

References

  1. 1.

    Bent, H. A. Structural chemistry of donor–acceptor interactions. Chem. Rev. 68, 587–648 (1968).

  2. 2.

    Desiraju, G. R. & Harlow, R. L. Cyano–halogen interactions and their role in the crystal structures of the 4-halobenzonitriles. J. Am. Chem. Soc. 111, 6757–6764 (1989).

  3. 3.

    Amico, V., Meille, S. V., Corradi, E., Messina, M. T. & Resnati, G. Perfluorocarbon−hydrocarbon self-assembling. 1D infinite chain formation driven by nitrogen···iodine interactions. J. Am. Chem. Soc. 120, 8261–8262 (1998).

  4. 4.

    Legon, A. C. π-Electron ‘donor–acceptor’ complexes BClF and the existence of the ‘chlorine bond’. Chem. Eur. J. 4, 1890–1897 (1998).

  5. 5.

    Valerio, G., Raos, G., Meille, S. V., Metrangolo, P. & Resnati, G. Halogen bonding in fluoroalkylhalides: a quantum chemical study of increasing fluorine substitution. J. Phys. Chem. A 104, 1617–1620 (2000).

  6. 6.

    Cavallo, G. et al. The halogen bond. Chem. Rev. 116, 2478–2601 (2016).

  7. 7.

    Li, B., Zang, S. Q., Wang, L. Y. & Mak, T. C. W. Halogen bonding: a powerful, emerging tool for constructing high-dimensional metal-containing supramolecular networks. Coord. Chem. Rev. 308, 1–21 (2016).

  8. 8.

    Berger, G., Soubhye, J. & Meyer, F. Halogen bonding in polymer science from crystal engineering to functional supramolecular polymers and materials. Polym. Chem. 6, 3559–3580 (2015).

  9. 9.

    Mukherjee, A., Tothadi, S. & Desiraju, G. R. Halogen bonds in crystal engineering: like hydrogen bonds yet different. Acc. Chem. Res. 47, 2514–2524 (2014).

  10. 10.

    Breugst, M., Von Der Heiden, D. & Schmauck, J. Novel noncovalent interactions in catalysis: a focus on halogen, chalcogen, and anion-π bonding. Synthesis 49, 3224–3236 (2017).

  11. 11.

    Nagorny, P. & Sun, Z. New approaches to organocatalysis based on C–H and C–X bonding for electrophilic substrate activation. Beilstein J. Org. Chem. 12, 2834–2848 (2016).

  12. 12.

    Bulfield, D. & Huber, S. M. Halogen bonding in organic synthesis and organocatalysis. Chem. Eur. J. 22, 14434–14450 (2016).

  13. 13.

    Wilcken, R., Zimmermann, M. O., Lange, A., Joerger, A. C. & Boeckler, F. M. Principles and applications of halogen bonding in medicinal chemistry and chemical biology. J. Med. Chem. 56, 1363–1388 (2013).

  14. 14.

    Beale, T. M., Chudzinski, M. G., Sarwar, M. G. & Taylor, M. S. Halogen bonding in solution: thermodynamics and applications. Chem. Soc. Rev. 42, 1667–1680 (2013).

  15. 15.

    Metrangolo, P. & Resnati, G. Halogen Bonding I (Springer, Berlin, 2015).

  16. 16.

    Metrangolo, P. & Resnati, G. Halogen Bonding II (Springer, Berlin, 2015).

  17. 17.

    Desiraju, G. R. et al. Definition of the halogen bond (IUPAC recommendations 2013). Pure Appl. Chem. 85, 1711–1713 (2013).

  18. 18.

    Clark, T., Hennemann, M., Murray, J. S. & Politzer, P. Halogen bonding: the σ-hole. J. Mol. Model. 13, 291–296 (2007).

  19. 19.

    Politzer, P., Lane, P., Concha, M. C., Ma, Y. & Murray, J. S. An overview of halogen bonding. J. Mol. Model. 13, 305–311 (2007).

  20. 20.

    Laurence, C., Graton, J., Berthelot, M. & El Ghomari, M. J. The diiodine basicity scale: toward a general halogen-bond basicity scale. Chem. Eur. J. 17, 10431–10444 (2011).

  21. 21.

    Wilbur, D. S. Enigmatic astatine. Nat. Chem. 5, 246–246 (2013).

  22. 22.

    Vaidyanathan, G. & Zalutsky, M. R. Applications of 211At and 223Ra in targeted alpha-particle radiotherapy. Curr. Radiopharm. 4, 283–294 (2011).

  23. 23.

    Vaidyanathan, G. & Zalutsky, M. R. Astatine radiopharmaceuticals: prospects and problems. Curr. Radiopharm. 1, 177–196 (2008).

  24. 24.

    Guérard, F., Gestin, J.-F. & Brechbiel, M. W. Production of [211At]-astatinated radiopharmaceuticals and applications in targeted α-particle therapy. Cancer Biother. Radiopharm. 28, 1–20 (2013).

  25. 25.

    Zalutsky, M. R., Reardon, D. A., Pozzi, O. R., Vaidyanathan, G. & Bigner, D. D. Targeted α-particle radiotherapy with 211At-labeled monoclonal antibodies. Nucl. Med. Biol. 34, 779–785 (2007).

  26. 26.

    Zalutsky, M. & Reardon, D. Clinical experience with α-particle-emitting 211At: treatment of recurrent brain tumor patients with 211At-labeled chimeric antitenascin monoclonal antibody 81C6. J. Nucl. Med. 49, 30–38 (2008).

  27. 27.

    Andersson, H. et al. Intraperitoneal α-particle radioimmunotherapy of ovarian cancer patients: pharmacokinetics and dosimetry of 211At-MX35 F(ab′)2—a phase I study. J. Nucl. Med. 50, 1153–1160 (2009).

  28. 28.

    Guérard, F., Lee, Y. S., Baidoo, K., Gestin, J. F. & Brechbiel, M. W. Unexpected behavior of the heaviest halogen astatine in the nucleophilic substitution of aryliodonium salts. Chem. Eur. J. 22, 12332–12339 (2016).

  29. 29.

    Champion, J. et al. Astatine standard redox potentials and speciation in acidic medium. J. Phys. Chem. A 114, 576–582 (2010).

  30. 30.

    Sergentu, D. C. et al. Advances on the determination of the astatine Pourbaix diagram: predomination of AtO(OH)2 over At in basic conditions. Chem. Eur. J. 22, 2964–2971 (2016).

  31. 31.

    Guo, N. et al. The heaviest possible ternary trihalogen species, IAtBr, evidenced in aqueous solution: an experimental performance driven by computations. Angew. Chem. Int. Ed. 128, 15595–15598 (2016).

  32. 32.

    Pilme, J. et al. QTAIM analysis in the context of quasirelativistic quantum calculations. J. Chem. Theory Comput. 10, 4830–4841 (2014).

  33. 33.

    Rothe, S. et al. Measurement of the first ionization potential of astatine by laser ionization spectroscopy. Nat. Commun. 4, 1835 (2013).

  34. 34.

    Fleig, T. & Sadlej, A. J. Electric dipole polarizabilities of the halogen atoms in 2 P 1/2 and 2 P 3/2 states: scalar relativistic and two-component configuration–interaction calculations. Phys. Rev. A 65, 032506 (2002).

  35. 35.

    Corson, D. R., MacKenzie, K. R. & Segre, E. Artificially radioactive element 85. Phys. Rev. 58, 672 (1940).

  36. 36.

    Hermann, A., Hoffmann, R. & Ashcroft, N. W. Condensed astatine: monatomic and metallic. Phys. Rev. Lett. 111, 116404 (2013).

  37. 37.

    Champion, J. et al. Assessment of an effective quasirelativistic methodology designed to study astatine chemistry in aqueous solution. Phys. Chem. Chem. Phys. 13, 14984–14992 (2011).

  38. 38.

    Alkorta, I., Blanco, F., Solimannejad, M. & Elguero, J. Competition of hydrogen bonds and halogen bonds in complexes of hypohalous acids with nitrogenated bases. J. Phys. Chem. A 112, 10856–10863 (2008).

  39. 39.

    Hill, J. G. & Hu, X. Theoretical insights into the nature of halogen bonding in prereactive complexes. Chem. Eur. J. 19, 3620–3628 (2013).

  40. 40.

    Maurice, R. et al. Effective bond orders from two-step spin–orbit coupling approaches: the I2, At2, IO+, and AtO+ case studies. J. Chem. Phys. 142, 094305 (2015).

  41. 41.

    Pilmé, J., Renault, E., Ayed, T., Montavon, G. & Galland, N. Introducing the ELF topological analysis in the field of quasirelativistic quantum calculations. J. Chem. Theory Comput. 8, 2985–2990 (2012).

  42. 42.

    Sergentu, D., Amaouch, M., Pilmé, J., Galland, N. & Maurice, R. Electronic structures and geometries of the XF3 (X=Cl, Br, I, At) fluorides. J. Chem. Phys. 143, 114306 (2015).

  43. 43.

    Sergentu, D.-C., David, G., Montavon, G., Maurice, R. & Galland, N. Scrutinizing ‘invisible’ astatine: a challenge for modern density functionals. J. Comput. Chem. 37, 1345–1354 (2016).

  44. 44.

    Champion, J. et al. Investigation of astatine(III) hydrolyzed species: experiments and relativistic calculations. J. Phys. Chem. A 117, 1983–1990 (2013).

  45. 45.

    Kolář, M. H. & Hobza, P. Computer modeling of halogen bonds and other σ-hole interactions. Chem. Rev. 116, 5155–5187 (2016).

  46. 46.

    Mantina, M., Chamberlin, A. C., Valero, R., Cramer, C. J. & Truhlar, D. G. Consistent van der Waals radii for the whole main group. J. Phys. Chem. A 113, 5806–5812 (2009).

  47. 47.

    Wilbur, D. S. et al. Reagents for astatination of biomolecules: comparison of the in vivo distribution and stability of some radioiodinated/astatinated benzamidyl and nido-carboranyl compounds. Bioconjug. Chem. 15, 203–223 (2004).

  48. 48.

    Makvandi, M. et al. The pre-clinical characterization of an alpha-emitting sigma-2 receptor targeted radiotherapeutic. Nucl. Med. Biol. 43, 35–41 (2016).

  49. 49.

    Alliot, C., Cherel, M., Barbet, J., Sauvage, T. & Montavon, G. Extraction of astatine-211 in diisopropylether (DIPE). Radiochim. Acta 97, 161–165 (2009).

  50. 50.

    Lindegren, S., Bäck, T. & Jensen, H. J. Dry-distillation of astatine-211 from irradiated bismuth targets: a time-saving procedure with high recovery yields. Appl. Radiat. Isot. 55, 157–160 (2001).

  51. 51.

    Trummal, A., Lipping, L., Kaljurand, I., Koppel, I. A. & Leito, I. Acidity of strong acids in water and dimethyl sulfoxide. J. Phys. Chem. A 120, 3663–3669 (2016).

  52. 52.

    Straatsma, T. P. et al. NWChem, A Computational Chemistry Package for Parallel Computers v.5.1.1 (Pacific Northwest National Laboratory, Richland, 2008).

  53. 53.

    Peterson, K. A., Shepler, B. C., Figgen, D. & Stoll, H. On the spectroscopic and thermochemical properties of ClO, BrO, IO, and their anions. J. Phys. Chem. A 110, 13877–13883 (2006).

  54. 54.

    Peterson, K. A., Figgen, D., Goll, E., Stoll, H. & Dolg, M. Systematically convergent basis sets with relativistic pseudopotentials. II. Small-core pseudopotentials and correlation consistent basis sets for the post-d group 16–18 elements. J. Chem. Phys. 119, 11113–11123 (2003).

  55. 55.

    Stephens, P. J., Devlin, F. J., Chabalowski, C. F. & Frisch, M. J. Ab initio calculation of vibrational absorption and circular dichroism spectra using density functional force fields. J. Phys. Chem. 98, 11623–11627 (1994).

  56. 56.

    Zhao, Y. & Truhlar, D. G. Design of density functionals that are broadly accurate for thermochemistry, thermochemical kinetics, and nonbonded interactions. J. Phys. Chem. A 109, 5656–5667 (2005).

  57. 57.

    Dunning, J., Peterson, K. A. & Wilson, A. K. Gaussian basis sets for use in correlated molecular calculations. X. The atoms aluminum through argon revisited. J. Chem. Phys. 114, 9244–9253 (2001).

  58. 58.

    Dunning, T. H. Jr Gaussian basis sets for use in correlated molecular calculations. I. The atoms boron through neon and hydrogen. J. Chem. Phys. 90, 1007 (1989).

  59. 59.

    Kendall, R. A., Dunning, T. H. Jr & Harrison, R. J. Electron affinities of the first-row atoms revisited. Systematic basis sets and wave functions. J. Chem. Phys. 96, 6796 (1992).

  60. 60.

    Armbruster, M. K., Klopper, W. & Weigend, F. Basis-set extensions for two-component spin–orbit treatments of heavy elements. Phys. Chem. Chem. Phys. 8, 4862–4865 (2006).

  61. 61.

    Boys, S. & Bernardi, F. The calculation of small molecular interactions by the differences of separate total energies. Some procedures with reduced errors. Mol. Phys. 19, 553–566 (1970).

Download references

Acknowledgements

This work was supported in part by grants from the French National Agency for Research called ‘Investissements d’Avenir’ (ANR-11-EQPX-0004, ANR-11-LABX-0018). The work was carried out using HPC resources from GENCI-CINES/IDRIS (grant 2016-x2016085117) and from CCIPL (Centre de Calcul Intensif des Pays de la Loire). The authors acknowledge the GIP ARRONAX for the production of At-211.

Author information

Affiliations

  1. SUBATECH, UMR CNRS 6457, IN2P3/IMT Atlantique/Université de Nantes, Nantes, France

    • Ning Guo
    • , Rémi Maurice
    • , David Teze
    • , Julie Champion
    •  & Gilles Montavon
  2. CEISAM, UMR CNRS 6230, Université de Nantes, Nantes, France

    • Jérôme Graton
    •  & Nicolas Galland

Authors

  1. Search for Ning Guo in:

  2. Search for Rémi Maurice in:

  3. Search for David Teze in:

  4. Search for Jérôme Graton in:

  5. Search for Julie Champion in:

  6. Search for Gilles Montavon in:

  7. Search for Nicolas Galland in:

Contributions

N.Guo, J.C., D.T., J.G., R.M. and G.M. conceived and performed the experimental study. D.T., R.M., J.G. and N.Galland conceived and performed the computational studies. All authors jointly discussed the results and their interpretation, and participated in writing the manuscript.

Competing interests

The authors declare no competing interests.

Corresponding authors

Correspondence to Gilles Montavon or Nicolas Galland.

Supplementary information

  1. Supplementary Information

    Supplementary Figures 1–4,Tables 1 and 2and  Structures 1–3

About this article

Publication history

Received

Accepted

Published

DOI

https://doi.org/10.1038/s41557-018-0011-1