Toward Organometallic Tc-99m Imaging Agents: Synthesis of Water-Stable Tc-99-NHC Complexes

(TcO2)-Tc-99-O-V-NHC complexes containing monodentate and bidentate N-heterocyclic carbenes (NHCs) have been prepared by the reactions of TcO(glyc)(2)](-) (glyc = ethyleneglycolato) with 1,3-dimethylimidazoline-2-ylidene (L1), 1,1'-methylene-3,3'-dimethyl-4,4'-diimidazoline-2,2'-diylidene (L2), and 1,1'-methylene-3,3'-diethyl-4,4'-diimidazoline-2,2'-diylidene (L3) in THF. The resulting complexes were fully characterized and their stabilities investigated. While complexes with monodentate NHCs only are hydrolytically unstable, complexes containing bidentate NHCs are water-stable over a broad pH range. The high water stability allows interconversion of the {(TcO2)-Tc-99-O-V}(+) core into {(TcOCl)-Tc-99-O-V}(2+) with HCl as the H+ and Cl- source. An alternative procedure to obtain (TcO2)-Tc-99-O-V-NHC complexes is the in situ deprotonation of imidazolium salts, enabling the preparation of (TcO2)-Tc-99-O-V-NHC compounds without free NHCs, thus increasing the scope of NHC ligands drastically. The remarkable stability and pH-controllable reactivity of the new complexes underlines the potential of NHCs as stabilizing ligands for Tc-99 complexes and paves the way for the first Tc-99m-NHC complexes in the future.