Rhenium and Technetium Tricarbonyl Complexes of N-Heterocyclic Carbene Ligands

A strategy for the conjugation of N-heterocyclic carbene (NHC) ligands to biomolecules via amide bond formation is described. Both 1-(2-pyridyl)imidazolium or 1-(2-pyridyl)benzimidazolium salts functionalized with a pendant carboxylic acid group were prepared and coupled to glycine benzyl ester using 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimide. A series of 10 rhenium(I) tricarbonyl complexes of the form [ReX(CO)(3)((C) over capN)] ((C) over capN is a bidentate NHC ligand, and X is a monodentate anionic ligand: Cl-, RCO2- were synthesized via a Ag2O transmetalation protocol from the Re(I) precursor compound Re(CO)(5)Cl. The synthesized azolium salts and Re(I) complexes were characterized by elemental analysis and by H-1 and C-13 NMR spectroscopy, and the molecular structures for one imidazolium salt and seven Re(I) complexes were determined by single-crystal X-ray diffraction. H-1 NMR and mass spectrometry studies for an acetonitrile-d(3) solution of [ReCl(CO)(3)(1-(2-pyridyl)-3-methylimidazolylidene)] show that the monodentate chloride ligand is labile and exchanges with this solvent yielding a cationic acetonitrile adduct. For the first time the labeling of an NHC ligand with technetium-99m is reported. Rapid Tc-99m labeling was achieved by heating the imidazolium salt 1-(2-pyridyl)-3-methylimidazolium iodide and Ag2O in methanol, followed by the addition of fac-[Tc-99m(OH2)(3)(CO)(3)](+). To confirm the structure of the Tc-99m-labeled complex, the equivalent Tc-99 complex was prepared, and mass spectrometric studies showed that the formed Tc complexes are of the form [Tc-99m/99(CH3CN)(CO)(3)(1-(2-pyridyl)-3-methylimidazolylidene)](+) with an acetonitrile molecule coordinated to the metal center.