Convenient route leading to neutral fac-M(CO)3(NNO) complexes (M = Re, 99mTc) coupled to amine pharmacophores

Abstract

The synthesis and characterization of three neutral tricarbonyl fac-M(CO)3(NNO) (M = Re, 99mTc) complexes based on the picolylamine N,N-diacetic acid (PADA) ligand is reported. One of the two carboxylate groups of the PADA ligand is efficiently and conveniently derivatized with an amine nucleophile through the use of the PADA anhydride. In this work, aniline, benzylamine and pyrrolidine were used as model amine nucleophites. The rhenium complexes were synthesized using the [NEt 4]2[Re(CO)3Br3] precursor and fully characterized by elemental analysis, spectroscopic methods, and X-ray crystallography. The analogous technetium-99m complexes were also prepared quantitatively using the (99mTc(CO)3(H2O) 3]+ precursor. The reaction scheme presented for the synthesis of the fac-M(CO)3(NNO) (M = Re, 99mTc) complexes can be applied to the development of target-specific radiopharmaceuticals because, in principle, any bioactive pharmacophore bearing an amine group can be used in the place of the model amine nucleophiles. © 2008 American Chemical Society