Molecular electrostatic potentials and noncovalent interactions

σ‐Holes and π‐holes are two types of regions of lower electronic density that are frequently found in molecules. There are often positive electrostatic potentials associated with them, through which the molecule can interact attractively with negative sites to form noncovalent bonds. The Hellmann–Feynman theorem shows that these interactions are Coulombic, where this must be understood to include polarization as well as electrostatics. Computed molecular electrostatic potentials have played major roles in elucidating the natures of σ‐hole and π‐hole bonding, but two key issues must be kept in mind: (1) the electrostatic potential at any point r reflects not only the electronic density at r but also contributions from all of the nuclei and electrons in the molecule; thus, the potential in a region does not necessarily correlate with the electronic density in that region. (2) When a molecule begins to interact with another molecule, ion, and so on, its electronic density and hence its electrostatic potential are immediately influenced to some extent by the electric field of the other entity. This induced polarization may significantly affect the molecule's interactive behavior. Both of these issues are discussed. WIREs Comput Mol Sci 2017, 7:e1326. doi: 10.1002/wcms.1326 This article is categorized under: Structure and Mechanism > Molecular Structures Structure and Mechanism > Computational Biochemistry and Biophysics Structure and Mechanism > Computational Materials Science