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

Abstract

²¹¹ At is a highly attractive radionuclide for alpha-particle therapy of cancers, provided it is firmly bound to a suitable targeting agent. In recent years, various radiolabeled gold nano-objects have been evaluated in vitro and in vivo, relying 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 of group IX metals was rationalized. This instability appears to correlate with increasing bond ionicity. Finally, the ubiquitous charge-shift character of the Au–At bond emerges as the cornerstone of the very promising radiolabeling of gold nanoplatforms.