Symmetric Halogen Bonding is Preferred in Solution
Journal article, 2012

Halogen bonding is a recently rediscovered secondary interaction that shows potential to become a complementary molecular tool to hydrogen bonding in rational drug design and in material sciences. Whereas hydrogen bond symmetry has been the subject of systematic studies for decades, the understanding of the analogous three-center halogen bonds is yet in its infancy. The isotopic perturbation of equilibrium (IPE) technique with 13C NMR detection was applied to regioselectively deuterated pyridine complexes to investigate the symmetry of [N−I−N]+ and [N−Br−N]+ halogen bonding in solution. Preference for a symmetric arrangement was observed for both a freely adjustable and for a conformationally restricted [N−X−N]+ model system, as also confirmed by computation on the DFT level. A closely attached counterion is shown to be compatible with the preferred symmetric arrangement. The experimental observations and computational predictions reveal a high energetic gain upon formation of symmetric, three-center four-electron halogen bonding. Whereas hydrogen bonds are generally asymmetric in solution and symmetric in the crystalline state, the analogous bromine and iodine centered halogen bonds prefer symmetric arrangement in solution.


Anna-Carin Carlsson

University of Gothenburg

Jürgen Gräfenstein

University of Gothenburg

Adnan Budnjo

University of Gothenburg

Jonas Bergquist

Alavi Karim

University of Gothenburg

Roland Kleinmaier

University of Gothenburg

Ulrika Brath

University of Gothenburg

Mate Erdelyi

University of Gothenburg

Journal of the American Chemical Society

0002-7863 (ISSN) 1520-5126 (eISSN)

Vol. 134 5706-5715

Subject Categories

Medicinal Chemistry

Organic Chemistry



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