Formation Of Gold-Astatine Bonds in N-Heterocyclic Carbene Complexes

With the purpose of exploring alternatives to the poorly stable astatoaryl bond found in most ²¹¹At-labeled radiopharmaceuticals, the coordination between astatine and metal-NHC (NHC = N-heterocyclic carbene) complexes was investigated. To orient this work, relativistic DFT calculations were performed, highlighting a superiority of gold(I) over rhodium(I) and iridium(I), both regarding the strength of the metal-astatine bond and the metal's preference for astatine over other halogens. The DFT calculations also revealed a more stable metal-astatine bond with electron-withdrawing NHCs. Accordingly, two Au(I) complexes, [AuCl(IPr)] (IPr = N,N'-bis[2,6-(di-isopropyl)phenyl]imidazol-2-ylidene) and [AuCl(IAd)] (IAd = N,N'-bis[adamantyl]imidazol-2-ylidene) were radiolabeled by halide exchange in excellent radiochemical yields with iodine-125 and astatine-211 in a water/acetonitrile mixture with a reducing agent. While the adamantyl-substituted complex was not investigated further due to its lack of solubility in aqueous or semi aqueous media, the stability of [Au²¹¹At(IPr)] in the presence of phosphate-buffered saline was evaluated and proved excellent (96% after two half-lives), encouraging further studies with relevant cancer-targeting vectors.