Evaluating Halogen-Bond Strength as a Function of Molecular Structure Using Nuclear Magnetic Resonance Spectroscopy and Computational Analysis

Abstract

Halogen bonding (XB) is a highly directional, noncovalent intermolecular interaction between a molecule (XB donor) presenting a halogen with an electron-deficient region or sigma hole (σhole) and an electron-rich or Lewis-base molecule (XB acceptor). A systematic, experimental, and theoretical study of solution-phase XB strength as a function of the molecular structure for both XB donor and acceptor molecules is presented. The impact of specific structural features is assessed using 19 F and 1 H nuclear magnetic resonance (NMR) titrations to determine association constants, density functional theory calculations for interaction energies and bond lengths, as well as 19 F− 1 H HOESY NMR measurements of intermolecular cross-relaxation between the interacting XB donor−acceptor adducts. For XB donor molecules (perfluoro-halogenated benzenes), results indicate the critical importance of iodine coupled with electron-withdrawing entities. Prominent structural components of XB acceptor molecules include a central atom working in conjunction with a Lewisbase atom to present high electron density directed at the σ-hole (e.g., tributylphosphine oxide). Additionally, larger surrounding aliphatic R groups (e.g., butyl and octyl) were found to significantly stabilize strong XB, particularly in solvents that promote the interaction. With a more thorough understanding of structure-optimized XB, one can envision harnessing XB interactions more strategically for specific design of optimal materials and chemical applications.

Influence of Substituents in the Benzene Ring on the Halogen Bond of Iodobenzene with Ammonia

“…[81] Each of several halogen atoms was placed on a phenyl ring, either unsubstituted or perfluorinated benzene. [41] The latter were found to engage in stronger XBs in an experimental setting, consistent with the calculations described above.…”

“…The accuracy of this combined approach has been documented in the past for halogen bonds and closely related interactions. [41,[45][46][47][48][49][50][51][52] The I center was represented by the relativistic aug-cc-pVDZ-PP pseudopotential. Quantum calculations made use of the Gaussian 16 [53] package.…”

“…There have been some initial indications that the NMR spectra of halogen bonded systems are connected in some way to the strength of each such bond. [30,35,[41][42][43][44][45] However, the application of spectroscopy to halogen bonding remains in its infancy. Another important goal of the present work is to advance this idea, using substituted halobenzenes as an ideal testbed.…”

Chalcogen Bonding with Diaryl Ditellurides: Evidence from Solid State and Solution Studies.

“…The mixture of 3 and Et 3 PO in cyclohexane showing the highest value of K a (Table 3, entry 5) was then considered in order to detect the Te⋅⋅⋅O interaction by 2D NMR. We wondered if 19 F− 1 H HOESY could be used to trace the putative spatial proximity of Et 3 PO hydrogens with ditelluride fluorines in 3 ⋅⋅⋅OPEt 3 adduct [39] . Unfortunately, the HOESY spectrum of the mixture composed of ditelluride 3 and 10 equivalents of Et 3 PO in cyclohexane‐ d12 did not show any cross‐peak that could be assigned to H−F spatial proximity.…”

Revealing Intra- and Intermolecular Interactions Determining Physico-Chemical Features of Selected Quinolone Carboxylic Acid Derivatives

“…In terms of interaction energy, they can be classified as only a little less strong than HBs, and their strength grows as polarizability of the halogen atom increases. Among further important factors that have an impact on halogen bond energy is the presence of electron-withdrawing groups near the halogen atom—the larger the electron-withdrawing effect, the more positive the electrostatic potential hole and the stronger the interaction of the halogen with the electron-rich entity [ 37 , 38 , 39 , 40 ]. Splendid examples of these effects are illustrated in the case of CH 3 Cl and CF 3 Cl molecules, where, in the absence of fluorine atoms, the -hole on the chlorine atom does not even exist [ 41 , 42 ].…”