Aqueous synthesis of derivatized cyclopentadienyl complexes of technetium and rhenium directed towards radiopharmaceutical application

Half-sandwich complexes of the type (RCOCp)M(CO)₃] with M ) Re and ^99(m)Tc were synthesized from [M(OH₂)_3-(CO)₃]⁺ in water. The R group can be an organic residue or a receptor binding biomolecule with a spacer to cyclopentadienyl (Cp). This provides a general route to Cp complexes of technetium without the need for starting from [TcBr(CO)₅].
The X-ray structure of [{C_6H5CH₂COC₅H₄}Tc(CO)₃] has been elucidated. The compound crystallizes in the monoclinic space group P2₁/c with a = 16.1454(9), b = 7.6300(6), and c = 12.3922(7) Å and beta = 107.792(6)°. We have chosen a serotonergic receptor ligand (WAY) as an example for the derivatization of Cp with a bioactive molecule. WAY is linked to Cp by an aliphatic chain of variable length. The half-sandwich complexes were prepared from water and organic solvents. The structure of [(WAY4-Cp)Re(CO)₃] could be elucidated. The compound crystallizes in the monoclinic space group P2₁/c with a = 15.7112(6), b = 6.8775(3), and c = 25.5217(12) Å and beta = 103.778(5)°. Quantification of inhibition constants gave a clear structure-activity relationship. A single methylene group between the receptor binding site and the half-sandwich complex gave an IC₅₀ of 217 nM for T_1A, whereas a butylene linker resulted in retention of the inhibition constant with an IC₅₀ of 6 nM with respect to underivatized WAY. For use as radiopharmaceuticals, the compounds have also been prepared with ^99mTc in quantitative yield.