Rhenium and Technetium Tricarbonyl Complexes of N‑Heterocyclic Carbene Ligands

Abstract

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(ĈN)] (ĈN 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)₅Cl. The synthesized azolium salts and Re­(I) complexes were characterized by elemental analysis and by ¹H and ¹³C NMR spectroscopy, and the molecular structures for one imidazolium salt and seven Re­(I) complexes were determined by single-crystal X-ray diffraction. ¹H NMR and mass spectrometry studies for an acetonitrile-<i>d</i>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 <i>fac</i>-[^99mTc­(OH₂)₃(CO)₃]⁺. To confirm the structure of the ^99mTc-labeled complex, the equivalent ⁹⁹Tc complex was prepared, and mass spectrometric studies showed that the formed Tc complexes are of the form [^{99<i>m</i>/99}Tc­(CH₃CN)­(CO)₃(1-(2-pyridyl)-3-methylimidazolylidene)]⁺ with an acetonitrile molecule coordinated to the metal center