Synthesis and spectroscopic characterization of two azatetrahydrochrysenes as potential fluorescent ligands for the estrogen receptor

In an effort to improve upon the spectroscopic characteristics of donor-acceptor tetrahydrochrysene systems that we have previously prepared as fluorescent ligands for the estrogen receptor, we have synthesized two aza analogs as receptor ligand prototypes and characterized their absorbance and fluorescence spectra. 1-Aza-9-hydroxy-5,6,11,12-tetrahydrochrysene (4) and 1,3-diaza-9-hydroxy-5,6,11,12-tetrahydrochrysene (5) were prepared by convenient heterocyclization reactions on a known tricyclic ketone (6). The UV spectra of these heterocycles were quite insensitive to solvent polarity but showed marked red shifts under acidic or basic conditions. These heterocycles displayed complex fluorescence spectra, with emission bands around 400 nm in aprotic medium that shifted to longer wavelength in protic solvents. In many cases, acid and base caused strong red shifts in the emission, with large alterations in quantum yield; in some cases emission bands were shifted as far as 600 nm and dual-emission peaks were observed. Thus, these two azatetrahydrochrysenes show greater environmental sensitivity-especially to changes in pH-than do our previously described donor-acceptor tetrahydrochrysenes. The binding affinity of these ligand prototypes for the estrogen receptor, however, is low, indicating that other structure modifications will be required to make them useful fluorescent ligands for this receptor.