Dicarbonyl cis-[M(CO)(N,O)(C)(P)] (M = Re, Tc) Complexes with a New [2 + 1 + 1] Donor Atom Combination.

The synthesis and characterization of the dicarbonyl mixed ligand cis-[Re(CO)(quin)(cisc)(PPh)] complex, 4, where quin is the deprotonated quinaldic acid, cisc is cyclohexyl isocyanide, and PPh is triphenylphosphine, is presented. The synthesis of 4 proceeds in three steps. In the first, the intermediate fac-[Re(CO)(quin)(HO)] aqua complex 2 is generated from the fac-[NEt][Re(CO)Br] precursor, together with the brominated products fac-[Re(CO)(quinH)(Br)] 1a and fac-[NEt][Re(CO)(quin)(Br)] 1b, in low yield. In the following step, replacement of the aqua ligand of complex 2 by the monodentate isocyanide ligand leads to the formation of fac-[Re(CO)(quin)(cisc)], 3. In the third step replacement of the species trans to the isocyanide carbonyl group of 3 by a phosphine generates complex 4. The Re complexes 2-4 were prepared in high yield and fully characterized by elemental analysis, spectroscopic methods, and X-ray crystallography. At the technetium-99m (Tc) tracer level, the analogous complexes 3' and 4' were produced in high radiochemical purity, characterized by comparative reverse phase high-performance liquid chromatography and showed high resistance to transchelation by histidine or cysteine. This new [N,O][C][P] donor atom combination with the cis-[M(CO)] core (M = Re, Tc) is a promising scaffold for the development of novel diagnostic and therapeutic targeted radiopharmaceuticals.