Halogen bonding (X-bonding): A biological perspective

Authors

  • Matthew R. Scholfield,

    1. Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, Colorado 80523-1870
    Search for more papers by this author
    • These authors contributed equally to this work.

  • Crystal M. Vander Zanden,

    1. Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, Colorado 80523-1870
    Search for more papers by this author
    • These authors contributed equally to this work.

  • Megan Carter,

    1. Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, Colorado 80523-1870
    Search for more papers by this author
  • P. Shing Ho

    Corresponding author
    1. Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, Colorado 80523-1870
    • Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO 80523-1870
    Search for more papers by this author

Abstract

The concept of the halogen bond (or X-bond) has become recognized as contributing significantly to the specificity in recognition of a large class of halogenated compounds. The interaction is most easily understood as primarily an electrostatically driven molecular interaction, where an electropositive crown, or σ-hole, serves as a Lewis acid to attract a variety of electron-rich Lewis bases, in analogous fashion to a classic hydrogen bonding (H-bond) interaction. We present here a broad overview of X-bonds from the perspective of a biologist who may not be familiar with this recently rediscovered class of interactions and, consequently, may be interested in how they can be applied as a highly directional and specific component of the molecular toolbox. This overview includes a discussion for where X-bonds are found in biomolecular structures, and how their structure–energy relationships are studied experimentally and modeled computationally. In total, our understanding of these basic concepts will allow X-bonds to be incorporated into strategies for the rational design of new halogenated inhibitors against biomolecular targets or toward molecular engineering of new biological-based materials.

Ancillary