In chemistry, a halogen bond ( XB or HaB
Definition
Halogen bonds occur when a halogen atom is electrostatically attracted to a
Partial charge. Necessarily, the atom must be covalently bonded in an
Antipodes Sigma bond; the electron concentration associated with that bond leaves a positively charged "hole" on the other side.
Although all halogens can theoretically participate in halogen bonds, the σ-hole shrinks if the electron cloud in question
Polarizability or the halogen is so electronegative as to polarize the associated σ-bond.
Consequently halogen-bond propensity follows the trend
[Although hydrogen is sometimes considered a halogen, convention excludes from the category of halogen bonds. For a complete analysis, see .] F < Cl < Br < I.
There is no clear distinction between halogen bonds and expanded octet Bond order; what is superficially a halogen bond may well turn out to be a full bond in an unexpectedly relevant resonance structure.
Donor characteristics
A halogen bond is almost
Collinearity with the halogen atom's other, conventional bond, but the geometry of the electron-charge donor may be much more complex.
-
Multi-electron donors such as and prefer halogen bonds collinear with the lone pair and donor nucleus.
-
Pyridine derivatives tend to donate halogen bonds approximately coplanar with the ring, and the two C–N–X angles are about 120°.
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Carbonyl group, Thioketone, and selenocarbonyl groups, with a trigonal planar geometry around the Lewis donor atom, can accept one or two halogen bonds.
Ion are usually better halogen-bond acceptors than neutral species: the more dissociated an ion pair is, the stronger the halogen bond formed with the anion.
Comparison to other bond-like forces
A parallel relationship can easily be drawn between halogen bonding and
hydrogen bonding. Both interactions revolve around an
electron donor/electron acceptor relationship, between a halogen-like atom and an
Electron density one. But halogen bonding is both much stronger and more sensitive to direction than hydrogen bonding. A typical hydrogen bond has
Bond energy ; known halogen
bond energy range from 10–200 kJ/mol.
The σ-hole concept readily extends to pnictogen, chalcogen and aerogen bonds, corresponding to atoms of Groups Pnictogen, Chalcogen and Aerogen (respectively).
History
In 1814, Jean-Jacques Colin discovered (to his surprise) that a mixture of dry gaseous ammonia and iodine formed a shiny, metallic-appearing liquid. Frederick Guthrie established the precise composition of the resulting I
2···NH
3 complex fifty years later, but the physical processes underlying the molecular interaction remained mysterious until the development of Robert S. Mulliken's theory of inner-sphere and outer-sphere interactions.
In Mulliken's categorization, the intermolecular interactions associated with small partial charges affect only the "inner sphere" of an atom's electron distribution; the electron redistribution associated with
affects the "outer sphere" instead.
[
]
Then, in 1954, Odd Hassel fruitfully applied the distinction to rationalize the X-ray diffraction patterns associated with a mixture of 1,4-dioxane and bromine.
Dumas and coworkers first coined the term "halogen bond" in 1978, during their investigations into complexes of CCl4, CBr4, SiCl4, and SiBr4 with tetrahydrofuran, tetrahydropyran, pyridine, anisole, and di-n-butyl ether in organic solvents.
However, it was not until the mid-1990s, that the nature and applications of the halogen bond began to be intensively studied. Through systematic and extensive microwave spectroscopy of gas-phase halogen bond adducts, Legon and coworkers drew attention to the similarities between halogen-bonding and better-known hydrogen-bonding interactions.
In 2007, computational calculations by Politzer and Murray showed that an anisotropic electron density distribution around the halogen nucleus — the "σ-hole"
In 2020, Kellett et al. showed that halogen bonds also have a π-covalent character similar to metal coordination bonds.
Applications
Crystal engineering
The strength and directionality of halogen bonds are a key tool in the discipline of crystal engineering, which attempts to shape crystal structures through close control of intermolecular interactions.
Halogen bonds can stabilize copolymers
or induce
Mesophase in otherwise isotropic
.
Indeed, halogen bond-induced liquid crystalline phases are known in both alkoxystilbazoles
and
(pictured).
Alternatively, the
Steric effects of halogen bonds can cause bulky molecules to crystallize into
Porous material; in one notable case, halogen bonds between
iodine and aromatic
Pi Orbitals caused molecules to crystallize into a pattern that was nearly 40% void.
Controlled polymerization
Conjugated polymers offer the tantalizing possibility of organic molecules with a manipulable electronic band structure, but current methods for production have an uncontrolled topology. Sun, Lauher, and Goroff discovered that certain
ensure a linear polymerization of poly(diiododiacetylene). The underlying mechanism is a self-organization of the amides via hydrogen bonds that then transfers to the diiododiacetylene monomers via halogen bonds. Although pure diiododiacetylene crystals do not
Polymerization spontaneously, the halogen-bond induced organization is sufficiently strong that the cocrystals do spontaneously polymerize.
Biological macromolecules
: a short Br−O halogen bond contributes to inhibitor potency.
|left]]Most biological macromolecules contain few or no halogen atoms. But when molecules do contain halogens, halogen bonds are often essential to understanding molecular conformation. Computational studies suggest that known halogenated
form halogen bonds with
oxygen,
nitrogen, or
sulfur in vitro. Interestingly, oxygen atoms typically do not attract halogens with their
, but rather the
Pi Orbitals electrons in the
Carbonyl group or
amide group.
Halogen bonding can be significant in drug design as well. For example, inhibitor IDD 594 binds to human aldose reductase through a bromine halogen bond, as shown in the figure. The molecules fail to bind to each other if similar aldehyde reductase replaces the enzyme, or chlorine replaces the drug halogen, because the variant geometries inhibit the halogen bond.
Notes
Further reading
