Synthesis and stability of 2+1 complexes of N,N-diethylbenzoylthiourea with [M^I(CO) ₃]⁺ (M = Re, ^99mTc)

In the last two decades, the fac-[M^I(OH₂)₃(CO)₃]⁺ (M = Re, ^99mTc) core has been an important synthon in the development of new radiopharmaceuticals and methodologies. A bidentate N,N-diethylbenzoylthiourea (HEt₂btu, H1) ligand was reacted with fac-[M^I(OH₂)₃(CO)₃]⁺ as part of a 2+1 strategy consisting of a bidentate and a monodentate ligands to saturate the coordination sphere. When excess H1 was used in the reaction, an unusual 2+1 complex of fac-[Re^I(CO)₃(1)(H1)], 2, was isolated that contained two H1 ligands, OS bidentate and S monodentate in different protonation states. Equimolar concentrations of HEt₂btu and fac-[Re^I(CO)₃]⁺ generated the single addition of the ligand; however, isolation of the solid revealed a -sulfur-bridged dimer of fac-[Re^I(CO)₃1)]₂, 3. Reaction of H1 with fac-[M^I(OH₂)₃(CO)₃]⁺ followed by the addition of a monodentate ligand (i.e. pyridine, methyl imidazole, cyclohexyl isocyanide, triphenylphosphine) yielded the corresponding 2+1 fac-[M^I(CO)₃(1)(L)] complexes. Single-crystal X-ray structural analysis of the Re complexes revealed conformational differences of the ligand on the metal depending on the protonation state of the central amine in the protonated H1 versus 1 ligand. Comparison of these complexes with previous complexes and free H1 revealed significant shifts in the bond angles, bond lengths, and ligand planarity that are discussed further. The corresponding 2+1 fac-[^99mTc^I(CO)₃(1)(L)] complexes were also prepared in moderate to good yields and their stability examined by amino acid challenge studies.