Rhenium complexes of dimercaptosuccinic acid derivatives for targeted radiotherapy

This work is part of efforts to develop chelating agents for stable binding and easy conjugation of Re-188 to biologically interesting structures. Starting from the high in vivo stability of [¹⁸⁸ReO(DMSA)₂]^- we want to exploit this coordination system for the design of ¹⁸⁸ReO(V) chelates which are stable towards re-oxidation to perrhenate under conditions of radiopharmaceutical procedures. Therefore a new type of tetradentate ligand has been synthesized by bridging two molecules on N-N'-diisobutyl-2,3-dimercaptosuccinamide with N-(3-aminopropyl)propane-1,3diamine. The resulting stereoisomeric tetrathiolato S₄ligand forms anionic five-coordinated oxorhenium(V) complexes by ligand exchange reaction of NBu₄[ReOCl₄]in methanol. Without addition of base the compounds will be isolated as "betain", [ReO(S₄)], with the protonated nitrogen of the bridge as a internal "counter ion".
Two representatives have been characterized in solid state 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. The complexes are stereoisomeric regarding the junction of the triamine chain. The Re-188 labelling procedure runs fast, in good yields and under mild conditions, making the new complexes interesting as access to stable Re-188 radiotherapeutics.

T. Heinrich, W. Kraus, H.-J. Pietzsch et al. Inorg. Chem., 44, 9930-9937 (2005).