Halogens can interact with nucleophiles through a phenomenon known as halogen bonding (XB). XBs are closely related to hydrogen bonds (HBs): both interactions arise from the directional electrostatic attraction between a nucleophile's lone pair and an electron-deficient site — either a hydrogen atom in the case of HBs or a (typically heavy, i.e. iodine or bromine) halogen for XBs. The positively charged region that interacts with the nucleophile's lone pair is referred to as the σ-hole. XBs have numerous applications, including crystal engineering, advanced polymerization techniques, and organocatalysis. Their catalytic properties primarily stem from their bond-weakening effect on the XB acceptor: for instance, a carbonyl that accepts an XB becomes further polarized, thus weakening its C=O double bond. Consequently, a nucleophile is more likely to attack the carbonyl carbon due to the increased partial positive charge.

Current research on XBs involves not only computational chemistry but also high-resolution X-ray diffraction (XRD) experiments. In the latter, the electrostatic potential (ESP) can be derived from the XRD electron density. However, three-dimensional electron diffraction (3D ED) circumvents this detour by directly yielding the ESP map from the diffraction experiment. Because the ESP map is a directly observable quantity in 3D ED, the insights gained can be applied in areas where XBs are significant, such as in method development in computational chemistry or in tailoring XB adducts in crystal engineering. Moreover, these results can be extrapolated to facilitate predictable modifications of XB donors and adducts to fine-tune specific properties of the bond.

The FWF is supporting an early-stage career program (ESPRIT) awarded to Steven van Terwingen in Tim Gruene's group at the Institute of Inorganic Chemistry to explore the electrostatic potential of halogen bonds through electron diffraction. The project will involve the synthesis of novel halogen-bonded adducts, which will be investigated using electron diffraction, X-ray diffraction, and computational methods. Additionally, students are encouraged to apply for internships or to engage in Bachelor’s and Master’s theses related to this research.

• Grant DOI: 10.55776/ESP9899224