Substituent Effect and Its Halogen‐Atom Dependence of Halogen Bonding Viewed through Electron Density Changes

Abstract

Elucidating how the halogen-bonding ability and strength are controlled by the substituent effect and how this control depends on halogen atom will be essential for finelytuned design of functionally important molecules. Here, this problem is tackled by analyzing the electron density differences/changes for variously substituted halobenzenes. It is shown that the anisotropy of the electron distribution around the halogen atom, which is an important factor for halogen-bonding ability, is not much affected by the substituent effect and rather simply depends on the halogen atom, while the partial charge on the halogen atom, which is related to the bond dipole of the CÀ X bond, is significantly modulated by the substituent effect and gives rise to enhancement of the electrostatic potential on the line extended from the CÀ X bond. The properties related to the polarization effect are also discussed.

Elucidating the Role of Electron-Donating Groups in Halogen Bonding

“…Since the discovery of halogen bonds (XBs) in the 1800s, − significant advancements in the field have improved our understanding of halogen bond interactions in molecules, supramolecular structures, and biological systems. It has been reported throughout the literature that the strongest XB interactions occur when the halogen bond donor contains strong electron-withdrawing groups, a highly polarizable halogen atom, − and a significant s-character hybridization (sp > sp 2 > sp 3 ) of the atom covalently bonded to the principle halogen. − Such conditions generate an increased attraction between the halogen atom in the XB donor (Lewis acid) and the XB acceptor (Lewis base). This results from a noncovalent interaction between lone pairs on the acceptor and a depletion of electron density along the extension of the covalent bond between the halogen atom and the R-group (i.e., the σ-hole). − …”

Enhancement of Halogen Bond Strength by Intramolecular H-Bonds

“…These and many other attributes of the HB have been thoroughly elucidated over more than a century, and are laid out in countless papers and monographs. − The study of the parallel XB is advancing quickly, leading to the establishment of a number of general rules and principles that guide our understanding of this phenomenon. − It is commonly understood, for example, that this bond strengthens as the X atom grows larger, commonly attributed to an associated rise in its electropositivity and polarizability. The highly compact and electronegative F atom very rarely participates in a XB, and then only under certain limited conditions .…”