Integrated "3+1" oxorhenium(V) complexes as estrogen mimics.
The diagnosis and staging of breast cancer could be improved by the development of imaging radiopharmaceuticals that provide a noninvasive determination of the estrogen receptor (ER) status of tumor cells. Toward this goal, we have synthesized a number of integrated "3+1" oxorhenium(V) complexes designed to mimic estradiol and a class of nonsteroidal estrogens, the tetrahydrochrysenes (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, but steric hindrance of the secondary thiol prevented the formation of the complex with the disubstituted ligand. The three "3+1" oxorhenium(V) complexes prepared to mimic the THC class mimics represent the first pyridinedithiol rhenium complexes of their kind to be made. These complexes are quite stable to air and moisture. The target tridentate ligand was prepared from chelidamic acid, and the VT NMR of the rhenium complex displays interesting fluxional behavior. The binding affinities of these complexes for the estrogen 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.
Skaddan
M B
MB
Department of Chemistry, University of Illinois, 600 S. Mathews Avenue, Urbana, Illinois 61801, USA.
Katzenellenbogen
J A
JA
D000818:Animals; D002911:Chrysenes / Q000737:chemistry; D004967:Estrogens / Q000737:chemistry*; D005260:Female; D066298:In Vitro Techniques; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D018716:Molecular Mimicry; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry; D011960:Receptors, Estrogen / Q000378:metabolism*; D012211:Rhenium; D012756:Sheep; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D014599:Uterus / Q000378:metabolism
D002911:Chrysenes; D004967:Estrogens; D008024:Ligands; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; D011960:Receptors, Estrogen; D013438:Sulfhydryl Compounds; D012211:Rhenium