Experimental electron density studies of non-steroidal synthetic estrogens: Diethylstilbestrol and dienestrol

An experimental charge density analysis has been carried out on two synthetic estrogens, diethylstilbestrol (DES) and dienestrol (DNS), to further investigate the alignment and binding of estrogenic compounds to the estrogen receptor, and to also establish a relationship between the biological function and the electronic properties of steroidal and non-steroidal estrogens by analysis of their electron density distribution. X-ray diffraction data for DES and DNS were obtained using a Rigaku R-Axis Rapid high-power rotating anode diffractometer with a curved image plate detector at 20(1) K. The total electron density was modeled using the Hansen-Coppens multipole model. Relatively strong O···HO hydrogen bonds, weak O···HC hydrogen bonds, and a number of intermolecular H···H interactions were characterized from the topological analyses of the total electron density of DES and DNS. Mapping of the electrostatic potential onto the molecular surface revealed negative regions around all the hydroxyl oxygens, above and below the aromatic rings as expected from previous studies. A proposed alignment and binding of DES and DNS to the estrogen receptor is discussed in terms of the atomic charges and electrostatic potential derived from the electron density distribution.