Integrated "3+1" oxorhenium(V) complexes as estrogen mimics

The diagnosis and staging of breast cancer could be improved by the develop ment of imaging radiopharmaceuticals that provide a noninvasive determinati on of the estrogen receptor (ER) status of tumor cells. Toward this goal, w e have synthesized a number of integrated "3+1" oxorhenium(V) complexes des igned to mimic estradiol and a class of nonsteroidal estrogens, the tetrahy drochrysenes (THC). The monodentate component of the estradiol mimic is a p -hydroxyphenethyl thiol ligand with ethyl substituents at the benzylic and homobenzylic positions. Model complexes of this ligand were easily made, bu t steric hindrance of the secondary thiol prevented the formation of the co mplex with the disubstituted ligand. The three "3+1" oxorhenium(V) complexe s prepared to mimic the THC class mimics represent the first pyridinedithio l rhenium complexes of their kind to be made. These complexes are quite sta ble to air and moisture. The target tridentate ligand was prepared from che lidamic acid, and the VT NMR of the rhenium complex displays interesting fl uxional behavior. The binding affinities of these complexes for the estroge n receptor are low, and their lipophilicities are rather high. Nevertheless , our findings provide a further refinement of our understanding of ligand structure-binding affinity correlations for the estrogen receptor.