Unexpected behavior of the heaviest halogen astatine in the nucleophilic substitution of aryliodonium salts

摘要

Aryliodonium salts have become precursors of choice for the synthesis of ¹⁸F-labelled tracers for nuclear imaging. However little is known on the reactivity of these precursors with heavy halogenides, i.e. radioiodide and astatide at the radiotracer scale. Herein, we report the first comparative study of radiohalogenation of aryliodonium salts with [¹²⁵I]-iodide and [²¹¹At]-astatide. Initial experiments on a model compound highlight a higher reactivity of astatide compared to iodide that could not be anticipated from the trends previously observed within the halogen series. Kinetic studies indicate a significant difference in activation energy (Ea = 23.5 and 17.1 kcal/mol with ¹²⁵I⁻ and ²¹¹At⁻, respectively). Quantum chemical calculations support the hypothesis of a monomeric iodonium-astatide intermediate whereas radio-iodination occurs in a dimeric environment. The good to excellent regioselectivity of halogenation and high yields achieved with diversely substituted aryliodonium salts indicates that this class of compounds is a promising alternative to the stannane chemistry currently used for radiohalogen labeling of tracers in nuclear medicine.