Aqueous Synthesis of Derivatized Cyclopentadienyl Complexes of Technetium and Rhenium Directed toward 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 [{C6H5CH2COC5H4}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 β = 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
β = 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 HT1A, 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.