Study of Mixed Re(I)/99mTc(I) Thiosemicarbazonate Complexes: Estrogen Receptor Affinity and Stability in Biological Media

Abstract

AbstractNine potentially bidentate thiosemicarbazone (HLn) ligands and their tricarbonylrhenium(I) complexes, [ReY(HLn)(CO)3] (Y=Cl, Br), were synthesized and their binding affinity towards the alpha and beta receptors were determined using a competitive standard radiometric assay with [3H]‐estradiol. Even in the absence of a base, coordinated thiosemicarbazones can undergo deprotonation causing the release of the coordinated halide forming dimeric species, [Re2(Ln)2(CO)6].The observation of the formation of the dinuclear complex where the thiosemicarbazone ligand adopts the zwitterionic form, [Re2(HL9)2(CO)6]Br2, motivated the theoretical study of the relative stability of these species.Despite the ease of formation of the dimer complexes, it was possible to optimize a synthetic route to obtain the [2+1] complexes [Re(Ln)(pym)(CO)3] where pym is the monodentate ligand 4‐dimethylamino‐pyridine or 4‐hydroxy ‐pyridine. The inclusion of this additional ligand substantially improves the affinity against the receptors (in some cases against both).[99mTc(Ln)(pym)(CO)3] complexes were also prepared using [99mTc(H2O)(CO)3]+, an excess of HLn ligand and in the presence of pym. The radiochromatograms show the formation of the [2+1] complex but also the presence of species resulting from the substitution of pym by chloride and water. However, the ratio of intensities between the three signals remains constant with the variation of the relative concentration of the three monodentate ligands suggesting an equilibrium between the three complexes.