Halogen Bonding in Solution

Abstract

Because of its expected applicability for modulation of molecular recognition phenomena in chemistry and biology, halogen bonding has lately attracted rapidly increasing interest. As most of these processes proceed in solution, the understanding of the influence of solvents on the interaction is of utmost importance. In addition, solution studies provide fundamental insights into the nature of halogen bonding, including, for example, the relative importance of charge transfer, dispersion, and electrostatics forces. Herein, a selection of halogen bonding literature is reviewed with the discussion focusing on the solvent effect and the electronic characteristics of halogen bonded complexes. Hence, charged and neutral systems together with two- and three-center bonds are presented in separate sub-sections. Solvent polarity is shown to have a slight stabilizing effect on neutral, two-center halogen bonds while strongly destabilizes charged, two-center complexes. It does not greatly influence the geometry of three-center halogen bonds, even though polar solvents facilitate dissociation of the counter-ion of charged three-center bonds. The charged three-center bonds are strengthened by increased environment polarity. Solvents possessing hydrogen bond donor functionalities efficiently destabilize all types of halogen bonds, primarily because of halogen vs hydrogen bond competition. A purely electrostatic model is insufficient for the description of halogen bonds in polar systems whereas it may give reasonable correlation to experimental data obtained in noninteracting, apolar solvents. Whereas dispersion plays a significant role for neutral, two-center halogen bonds, charged halogen bond complexes possess a significant charge transfer characteristic.

Insights into halogen bond-driven enantioseparations

“…In contrast, increasing the size and positive nature of halogen's '-hole' dramatically enhances the strength of the electrostatic component of the halogen bonding interaction [50,51]. Moreover, despite a purely electrostatic model is insufficient for the description of halogen bonds in polar systems, it may give reasonable correlation to experimental data obtained in non-polar medium [16].…”

“…In fact, several studies applying IR spectroscopy, X-ray diffraction, solid state NMR, and computational modelling confirmed that alcohols can form HBs with the C O and NH functions of the polymer, resulting in a change of the polymer structure with respect to the presence of Hex [40]. On the other hand, solvents possessing HB donor functionalities destabilize all types of XBs, primarily because of halogen vs hydrogen bond competition [16]. On this basis, taking into account that the strength of polar interactions decreases following the order Hex EtOH > MeOH, whereas the strength of the hydrophobic interactions follows the opposite order, polar and hydrophobic contribution to enantioseparation could be evaluated separately.…”

Polysaccharide‐based chiral stationary phases as halogen bond acceptors: A novel strategy for detection of stereoselective σ‐hole bonds in solution

“…Although similar from the viewpoint of formation to hydrophilic hydrogen bond (HB), the XB is of hydrophobic nature, and this complementarity provides new opportunities for molecular recognition, particularly in solvated environment. Nevertheless, the exploration of solvent effects on XB has begun later compared to solid‐state studies, and to date the applications in solution are still challenging . Indeed, formation and detection of XBs in solution are more complicated as compared to the solid state because the interactions can be influenced by conformational freedom of the molecules, a less ordered medium, and solvent effects on both donor and acceptor .…”

Halogen-Bonded Co-Crystals of Aromatic N-oxides: Polydentate Acceptors for Halogen and Hydrogen Bonds

“…Halogen bonds are frequently studied using nitrogen compounds, which typically display monovalent N···X (X = I, Br) interactions and are well understood as crystal engineering tools for self-assembly processes. Their precedence from discrete structures to increased dimensionality through the controlled reactivity of substrates is well-reported [10][11][12][13]. In a solid-state XB complex, R−X···B−Z, where X is the donor and B is the acceptor atom, the ratio of the short distance between X and B atoms (d X-B ) to sum of the Van der Waals radii of X and B atoms (d vdW ) is defined as the normalized strength parameter, R XB = d X-B /d vdW [1].…”