Negative σ-Holes on Fluorine in Molecules Revisited: Halogen Bonding or Counterintuitive, Anti-Electrostatic Interactions?

Abstract

Halogen bonding develops when an electrophilic region associated with a covalently bonded halogen interacts attractively with a nucleophilic site on another same or different molecular entity. Here, we show that in many crystals in the Cambridge Structural Database, the intermolecular distances and directional features of F···F close contacts involve σ-hole-like regions on covalently bound fluorine. However, such interactions cannot readily be classified as classical halogen bonds, as the interacting fluorine atoms may lack a positive site (e.g., a positive σ-hole). In this context, we investigated directional F···F interactions involving HF, CH4−nFn (n = 1–4), and C6H6−nFn (n = 1–6) interacting with negative sites in the same or different partner interacting species using computational methods, which exhibit complex geometries reminiscent of σ-hole interactions. However, such interactions between sites of like polarity are more appropriately described as σ-hole-centered anti-electrostatic interaction motifs, driven in part by dispersion, rather than being recognized as conventional σ-hole-centered halogen bonds. This interpretation is supported by molecular electrostatic surface potential and symmetry-adapted perturbation theory analyses.