Scientists in the Czech Republic have developed a novel approach to assess the covalent nature of halogen bonds. This method, which evaluates the degree of electron sharing in these bonds, aims to contribute to ongoing debates about the physical characteristics of these crucial supramolecular interactions. Halogen bonds, similar to the more well-known hydrogen bonds, play a significant role in catalyst, drug, and materials design. They form between different molecules or within the same molecule when a nucleophilic region, such as a lone pair of electrons, on one atom interacts with the electrophilic region, the s hole, on a halogen atom. The strength of these bonds depends on the polarisability and electronegativity of the halogen (X) and the electron-withdrawing capacity of the group to which the halogen is bonded (R). Despite the understanding that halogen bonds are primarily electrostatically-driven noncovalent interactions, recent evidence suggests a significant covalent contribution. Robin Perutz, an inorganic chemist at the University of York, UK, notes that investigations into the covalent nature of these interactions typically involve examining crystal structures using techniques like x-ray diffraction or infrared (IR) spectroscopy. These methods reveal changes in the R–X bond length caused by halogen bonding. However, Radek Marek at Masaryk University and his colleagues propose a new approach using paramagnetic nuclear magnetic resonance (NMR) spectroscopy to probe the covalent nature of halogen bonds. Marek's team compared the 13C NMR spectra of halogen-bonded cocrystals with paramagnetic and diamagnetic metal complexes. They observed a significant shift in the peak corresponding to the carbon bonded directly with the halogen (C1) between the paramagnetic and diamagnetic metal cocrystals. This hyperfine shift is caused by interactions between nuclear and electron spins, including the Fermi contact interaction. Marek explains that the Fermi contact contribution to NMR shifts, related to intermolecular electron spin transmission, is an excellent indicator of electron sharing in halogen-bonded cocrystals. The study provides direct and highly sensitive experimental evidence for covalency in halogen bonds. While non-covalent interactions remain dominant, the team found that covalent interactions, or electron sharing, can contribute up to 25% of the total interaction energy. Perutz acknowledges the method's effectiveness but suggests further exploration. He questions why the team did not investigate the temperature dependence of paramagnetism to rule out other potential contributions. Additionally, Perutz recommends further NMR studies probing adjacently bonded fluorines, which could reveal even greater covalent details. He also inquires about the availability of more sensitive techniques, noting that there are other situations where larger shifts can be observed. Both Marek and Perutz emphasize the importance of refining our understanding of halogen bonding for more accurate modeling of catalyst, functional material, and pharmaceutical interactions.
