Novel Rhenium Chelate System Derived from Dimercaptosuccinic Acid for the Selective Labeling of Biomolecules

This work is part of an effort to develop chelating agents for stable binding and easy conjugation of Re-188 to
biologically interesting structures. Starting from the well-known in vivo stability of [188ReO(DMSA)2]-, we want to
exploit this coordination system for the design of 188ReO(V) chelates, which are stable toward reoxidation to perrhenate
and toward ligand exchange under all conditions of radiopharmaceutical development. Therefore, a new type of
tetradentate ligand has been synthesized by bridging two molecules of N,N‘-diisobutyl-2,3-dimercaptosuccinamide
with N-(3-aminopropyl)propane-1,3-diamine. The resulting stereoisomeric tetrathiolato S4 ligand of composition
(iBu)2N(O)C−C(SH)−C(SH)−C(O)NH−(CH2)3−NH−(CH2)3−NHC(O)−C(SH)−C(SH)−C(O)N(iBu)2 forms anionic five-coordinate oxorhenium(V) complexes by a ligand-exchange reaction of NBu4[ReOCl4] in methanol. In the absence
of a base, the compounds were isolated as “betaine”, [ReO(S4)], with the protonated nitrogen of the bridge serving
as an internal “counterion”. Two representatives have been fully characterized in both the solid and solution states
and found to adopt the expected square-pyramidal coordination geometry. The equatorial plane is formed by four
thiolate sulfur atoms, whereas the oxygen occupies the apical position. The orientation of the metal oxo group is
exo in relation to the carbamido groups in both isomers. Both complexes are stereoisomeric regarding the junction
of the triamine chain.