1,2-Diaryl-3,4-dihydronaphthalenes: photofluorogenic ligands for the estrogen receptor

1,2-Diaryl-3,4-dihydronaphthalene systems related to the Upjohn antiestrogen nafoxidine (U11, 110A) (1) have high affinity for the estrogen receptor, but are essentially non-fluorescent. Upon u.v. irradiation, however, the cis-stilbene system within their structure undergo a photocyclization (2) followed by a spontaneous oxidation, forming a dihydrobenzochrysene system (3) that is highly fluorescent, but is only weakly bound by the estrogen receptor. This system can be oxidized further to the benzochrysene system, which exhibits similar fluorescence. The 1,2-diarylnaphthalene systems, obtained by direct oxidation of the dihydronaphthalenes, however, do not undergo photocyclization. The binding affinity of these derivatives for the estrogen receptor appears to be related to their degree of non-planarity and can be correlated with their molecular surface area. This facile photochemical conversion of a high-affinity ligand to a highly fluorescent species offers a new approach to the design of fluorescent estrogens.