(neutral to ionic) between the TTF and tetracyanoquinodimethane derivatives, thereby directly showing the influence of charge on halogen bond strength [25]. The halogen bond has also played a role in the construction of nitroxide materials [100-102] and has been explored alongside ferromagnetic coordination polymers [103].
Figure 1.11 Representative examples of N‐iodoimide halogen bond donors (a). Scheme of halogen bond cocrystal/salt concept transfer (b).
((b) Modified from Makhotkina et al. [105].)
1.3.4 Alternative Motifs and Solid‐state Reactivity
The use of alternative or less common designs in halogen bonding has been reviewed [104]. Some of the less common donors include N‐iodoimides (Figure 1.11a), which have been shown to be powerful halogen donors for a diverse range of acceptors [106-109]. In one example, Fourmigué and coworkers demonstrate that altering the donor and acceptor of these N‐iodoimides can be used to demonstrate the cocrystal to salt continuum, a topic generally reserved for proton transfer between a hydrogen bond donor and acceptor. In the context of halogen bonding, it is iodine transfer that results in a salt (Figure 1.11b) [105] and has also been the subject of a charge density analysis study [109]. Another alternative halogen bond is the three‐center‐four‐electron halogen bond of the type [NIN]+. These unique motifs are often compared with the low barrier hydrogen bonds of the type [NHN]+ and are the subject of an ensuing chapter.
Halogen bonds have also been used to mediate crystalline state reactivity. The first example of a photomediated [2 + 2] olefin cycloaddition was presented by Metrangolo and coworkers [110]. Here, a tetratopic halogen bond donor arranged trans‐1,2‐bis(4‐pyridyl)ethene for cycloaddition using CI⋯N halogen bonds (Figure 1.12, top). Similar tactics by Sinnwell and MacGillivray highlighted the use of a ditopic halogen bond acceptor to arrange the olefin‐containing halogen bond donors, diiodooctafluorostilbene (Figure 1.12, bottom) [112]. Once again, CI⋯N halogen bonds were employed to properly arrange the reactants. Only recently has a halogen bond cocrystal mediated a single‐crystal‐to‐single‐crystal transformation of an olefin cycloaddition [111]. The halogen bond has also been used to arrange polyacetylenes for polymerization. For example, the cocrystallization of 1,4‐diiodo‐1,3‐butadiyne with either dipyridine or dinitrile oxalamide derivatives produced 2D networks driven by both hydrogen bond and halogen bonds [113] (Figure 1.13). The pyridine derivative only polymerized when subjugated to higher pressures, whereas the nitrile derivative polymerizes spontaneously at room temperature (Figure 1.13). Solid‐state reactivity can also occur by mechanochemistry or solvent‐assisted grinding. For example, halogen bond‐mediated cocrystals were produced with mechanochemistry using 1,4‐diiodotetrafluorobenzene and 1,4‐dibromotetrafluorobenzene halogen bond donors and analyzed through powder diffraction and single‐crystal analysis [114].
Figure 1.12 Examples of halogen bond mediated [2 + 2] photodimerization of olefins in the solid state.
Source: From Sinnwell et al. [111]. Licensed under CC BY 2.0.
1.3.5 Crystallographic Studies Conclusion
Solid‐state evaluations of the halogen bond are vast, with numerous reviews written on the topic [7,58–65]. This section provided a topical survey highlighting some of the diversity within the field. However, one significant topic that was purposely omitted was halogen bonding to anions [115,116] as many of the later chapters include aspects of halogen bonding to anions in solution (e.g. quantification, receptors, transport, catalysis). Other solid‐state halogen bonding topics that have been omitted for brevity include solid‐state NMR [117,118], porous crystalline materials [119–121], crystalline rotors [122,123], polyhalides [124–126], cosublimation [127], energetic cocrystals [127], and intramolecular halogen bonding [128]. Looking forward, crystallography will continue to be an important research tool that complements studies of halogen bonding in solution.
Figure 1.13 Cocrystallization components and pre‐polymerization structures of 1,4‐diiodo‐1,3‐butadiyne with oxalamide derivatives. CCDC ref codes: WANNUV01 (left), CEKFUU (right).
1.4 Computational Studies
1.4.1 Introduction
Computational chemistry has proven valuable to understanding the fundamental nature of the halogen bond and frequently complements observed experimental data. Computational studies have shown that different components (e.g. charge transfer, electrostatics, dispersion) contribute to the interaction and that the relative makeup depends on the nature of the halogen bond donor (e.g. inorganic, organic, neutral, charged assisted) and acceptor (e.g. neutral, charged, soft or hard Lewis base). In this section, the forces contributing to the halogen bond interaction and an overview of in silico methods used to study the halogen bond will be surveyed. For an in‐depth look, reviews on computational halogen bonding theory in small molecule [8,129,130] and biological [131] systems have been published. Additionally, techniques to study the halogen bond (and other σ‐hole interactions) in silico have been reviewed by Kozuch and Bickelhaupt [132] and Hobza [133].
1.4.2 Electrostatics of the Halogen Bond and the σ‐Hole
One description of the halogen bond is rooted in the electron distribution of an isolated molecule within a ground state. As a polarizable halogen forms a covalent bond with an electron‐withdrawing group, a rearrangement of electrons results in electron‐rich and electron‐poor regions within the newly formed species. Consequently, the halogen adopts a spheroid shape, with the radius of the halogen extending from the covalent bond to the outer surface being smaller than the radius measured normal to the covalent bond (Figure 1.1b). The term “polar flattening” is sometimes used to describe the oblate shape of the electron cloud resulting from the depletion of electronic charge at the end of the halogen [134] and has been demonstrated in a CSD study [135] as well as by experimental charge density analysis [136,137]. Polar flattening is not limited to halogens, but instead applies to all atoms covalently bound to another atom. Computationally mapping this distortion of electronic density has become a routine task and is achieved by measuring the ESP surface of a molecule. To better understand what ESP maps are depicting, it is necessary to outline their construction:
Equation 1.1 Electrostatic potential.
