Stable astatine-metal bond in gold-based carriers for targeted alpha-particle therapy: role of charge-shift bonding

²¹¹At is a highly attractive radionuclide for alpha-particle therapy of cancers, provided it is firmly bounded to a suitable targeting agent. In recent years, various radiolabeled gold nano-objects have been evaluated in vitro and in vivo, drawing on the formation of a covalent bond between astatine and gold atoms. While stability was found for ²¹¹At-labeling of Au(I)-NHC (NHC = N-heterocyclic carbene) complexes, some issues were experienced with other soft metal Rh(I)- and Ir(I)-NHC complexes. By finely analyzing the nature of astatine-metal interactions with the theoretical tools of quantum chemical topology, the instability for group IX metals was rationalized. It appears quantified by increasing bond ionicity. Finally, the ubiquitous charge-shift character of the Au–At bond is the cornerstone of the very promising radiolabeling of gold nanoplatforms.