Formation Of Gold-Astatine Bonds in N-Heterocyclic Carbene Complexes
Résumé
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 radiolabelled 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 presence of phosphate buffered saline was evaluated and proved excellent (96% after two half‐lives) encouraging further studies with relevant cancer targeting vectors.
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