Interaction Nature and Computational Methods for Halogen Bonding: A Perspective

Halogen bonds are
noncovalent interactions that have been widely
used in many fields, including drug design, crystal engineering, and
material sciences. A clear understanding of the nature of halogen
bonding as well as the proper theoretical bonding description, especially
the development of efficient and accurate computational chemical methods
and their application in complex systems, is of great significance
to promote the development of related fields. In this perspective,
we reviewed the investigations of the nature of halogen bonding in
recent years and discussed the development of quantum mechanical,
molecular mechanical, and empirical scoring function methods in properly
describing halogen-bonding interactions, as well as their achievements
in corresponding areas. An evaluation on the performance of various
quantum mechanical and semiempirical quantum mechanical methods in
describing halogen bonds was also included, involving the DFT-D4 scheme
and the recently reported xTB methods. We hope this perspective may
be helpful, from the insights of computational tools and methods,
in providing reference and enlightenment for the application of halogen
bonds in fields like high-throughput virtual screening and rational
drug design.