Ion‐Pair Halogen Bonds in 2‐Halo‐Functionalized Imidazolium Chloride Receptors: Substituent and Solvent Effects

Abstract

The interaction of 2-halo-functionalized imidazolium derivatives (n-X ; X=Cl, Br, I) with a chloride anion through ion-pair halogen bonds (n-X⋅Cl) was studied by means of DFT and ab initio calculations. A method benchmark was performed on 2-bromo-1H-imidazol-3-ium in association with chloride (1-Br⋅Cl); MP2 yielded the best results when compared with CCSD(T) calculations. The interaction energies (ΔE) in the gas phase are high and, although the electrostatic interaction is strong owing to the ion-pair nature of the system, large X⋅⋅⋅Cl Wiberg bond orders and contributions from charge transfer (nCl- →σ*C-X) are obtained. These values drop considerably in chloroform and water; this shows that solvent plays a role in modulating the interaction and that gas-phase calculations are particularly unrealistic for experimental applications. The introduction of electron-withdrawing groups in the 4,5-positions of the imidazolium (e.g., -NO , -F) increases the halogen-bond strength in both the gas phase and solvent, including water. The effect of the substituents on the 1,3-positions (N-H groups) also depends on the solvent. The variation of ΔE can be predicted through a two-parameter linear regression that optimizes the weights of charge-transfer and electrostatic interactions, which are different in vacuum and in solvent (chloroform and water). These results could be used in the rational design of efficient chloride receptors based on halogen bonds that work in solution, in particular, in an aqueous environment.

Halogen bonding in differently charged complexes: basic profile, essential interaction terms and intrinsic σ-hole

“…4), revealing the stronger ability of the cationic donor to obtain electrons and that of the anionic acceptor to provide electrons in the formation of a XB. Hence, as expected, 18,52b remarkable electron transfer interaction takes place in the cation-anion complex, which is also indicated by the QTAIM analysis results (Tables S2-S4, ESI †), such that the corresponding net halogen bonding strength is the strongest while that of the anion-cation complex is the weakest in polar solvents (Table 3). Although the orbital interaction decreases for most systems in polar environments, it increases in the cation-cation complex, partially as a result of intramolecular charge redistribution (part 3.5).…”

“…Although overall binding energy (E bind ) has long been a classic parameter when discussing the strength of XBs, intermolecular Coulombic interaction has significant contributions to total binding strength, 18,21,22,52 especially in charged complexes (Table 1). A strategy of applying the classic point-to-point Coulombic formula via fixing the charges at specific points was considered to remove the background Coulombic interaction, and has been successfully utilized on charged XB systems to obtain net halogen bonding energy between the charged donor and acceptor.…”

“…in solvents). Solvents are found to affect the amount of electrons transferred as well, 18,57 and in general lead to less electron transfer in polar environments for chargeassisted XB complexes (e.g., cation-anion, neutral-anion and cation-neutral) and more for the others, which may explain the preference of polar solvents for the classic neutral-neutral halogen-bonded co-crystals. 59 All these observations from the natural population analysis (NPA) are similarly indicated by the Hirshfeld population analysis (HPA) (Tables S20-S22, ESI †) as well.…”

“…The XB binding strength could be even stronger between a cationic XB donor and an anionic XB acceptor, as reported by Riley et al 17 using DFT (oB97X-D/def2-TZVP) and the symmetry-adapted perturbation theory (SAPT) method, revealing extreme negative values up to about À80 kcal mol À1 in a vacuum. However, the strong ionpair XB may weaken considerably in solvents, 18 which should thus be taken into account to evaluate the binding strength more realistically. The solvent effects on the XB estimated using 19 F NMR titrations by Sarwar et al revealed that the purely electrostatic description of the XB may have limitations, 19 which was suggested by Huber et al as well.…”

Tackling Halogenated Species with PBSA: Effect of Emulating the σ-Hole

“…17,18 Moreover, they often bind to their biomolecular targets via halogen bonds (XBs), 19 which are non-covalent interactions of the type R-X• • • B (X = Cl, Br, I; B = Lewis base; R = substituent). 20 There are many known applications of XBs, 21,22 ranging from anion recognition [23][24][25][26] to rational drug design. 18,27,28 The origin of this interaction has been ascribed to the existence of a positive region at the tip of the halogen (fluorine is usually not considered), known as the σ-hole (Figure 1, A).…”