Halogen Bonding Interactions in Molecular Systems

Halogen bonding is a class of highly directional non-covalent interactions in which a halogen atom serves as an electron-accepting site and interacts with an electron-rich partner. The hallmark of this interaction is the anisotropic distribution of electron density around the halogen, giving rise to a region of positive electrostatic potential opposite the covalent bond—known as a σ-hole—which engages with lone-pair donors or π-systems. Beyond classical σ-hole bonding, recent work has unveiled π-hole interactions wherein halogen atoms display electrophilic character perpendicular to a molecular plane. These interactions complement hydrogen bonding and metal coordination in governing molecular recognition, crystal packing, self-assembly and catalysis. Their tunable strength and directionality have underpinned advances in supramolecular chemistry, drug design and functional materials, enabling precise control over molecular architecture, electronic properties and responsive behaviour under external stimuli.

Research from Nature Portfolio

Recent studies have challenged the view that halogen bonds are purely σ-symmetric and electrostatic. Advanced spectroscopic analysis of halogenated radical cation complexes has provided direct evidence for π-covalency in halogen bonds. Chlorine K-edge X-ray absorption measurements, combined with quantum-chemical modelling, revealed orbital mixing reminiscent of metal–ligand interactions rather than simple electrostatic attraction. This revised paradigm suggests that halogen bonds can be exploited to modulate electronic communication in conjugated systems, opening new avenues for the design of redox-active materials and electronic devices driven by directional π-interactions.

Halogen Bonding Interactions in Molecular Systems publication trend

The graph below shows the total number of articles in halogen bonding interactions in molecular systems across all publications each year (not limited to Nature Index journals).

Technical terms

Halogen bond: A non-covalent attraction between a region of positive electrostatic potential on a halogen atom and an electron-rich partner.

σ-Hole: An electron-deficient region opposite a covalent bond on a halogen atom that serves as a halogen-bond donor site.

π-Hole: An electrophilic region perpendicular to a molecular plane, enabling directional interactions with electron-rich sites.

Lewis base: An electron-pair donor species that interacts with an electrophilic site, such as a σ- or π-hole.

Electrostatic potential: A scalar field representing the energy of bringing a unit positive charge to a point around a molecule, guiding non-covalent interactions.

References

1. In Situ X‐Ray Techniques Unraveling Charge Distribution Induced by Halogen Bonds in Solvates of an Iodo‐Substituted Squaraine Dye. Advanced Science (2024).
2. Halogen Bond via an Electrophilic π-Hole on Halogen in Molecules: Does It Exist?. International Journal of Molecular Sciences (2024).
3. The Formation of σ-Hole Bonds: A Physical Interpretation. Molecules (2024).
4. π covalency in the halogen bond. Nature Communications (2020).
5. An Overview of Strengths and Directionalities of Noncovalent Interactions: σ-Holes and π-Holes. Crystals (2019).
6. Halogen Bonding: A Halogen-Centered Noncovalent Interaction Yet to Be Understood. Inorganics (2019).