Unexpected Behavior of the Heaviest Halogen Astatine in the Nucleophilic Substitution of Aryliodonium Salts.
Aryliodonium salts have become precursors of choice for the synthesis of (18) F-labeled tracers for nuclear imaging. However, little is known on the reactivity of these compounds with heavy halides, that is, radioiodide and astatide, at the radiotracer scale. In the first comparative study of radiohalogenation of aryliodonium salts with (125) I(-) and (211) At(-) , initial experiments on a model compound highlight the higher reactivity of astatide compared to iodide, which 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(-1) with (125) I(-) and (211) At(-) , respectively). Quantum chemical calculations suggest that astatination occurs via the monomeric form of an iodonium complex whereas iodination occurs via a heterodimeric iodonium intermediate. The good to excellent regioselectivity of halogenation and high yields achieved with diversely substituted aryliodonium salts indicate that this class of compounds is a promising alternative to the stannane chemistry currently used for heavy radiohalogen labeling of tracers in nuclear medicine.
Radioimmune & Inorganic Chemistry Section, Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, 20892, USA. francois.guerard@univ-nantes.fr.|Inserm U892, CNRS UMR6299, Université de Nantes, Nantes, France. francois.guerard@univ-nantes.fr.
François
http://orcid.org/0000-0001-9795-2785
F
Guérard
Center for Molecular Modeling, Division of Computational Bioscience, Center for Information Technology, National Institutes of Health, Bethesda, Maryland, 20892, USA.
Yong-Sok
YS
Lee
Radioimmune & Inorganic Chemistry Section, Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, 20892, USA.
Kwamena
K
Baidoo
Inserm U892, CNRS UMR6299, Université de Nantes, Nantes, France.
Jean-François
JF
Gestin
Radioimmune & Inorganic Chemistry Section, Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, 20892, USA.
Martin W
MW
Brechbiel
astatine; halogenation; iodonium salts; nucleophilic substitution; radiopharmaceuticals