Binding of Genistein to the Estrogen Receptor Based on an Experimental Electron Density Study

In a continuing effort to determine a relationship between the biological function and the electronic
properties of steroidal and nonsteroidal estrogens by analysis of the submolecular properties, an
experimental charge density study has been pursued on the nonsteroidal phytoestrogen, genistein. X-ray
diffraction data 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. Genistein packs in puckered sheets characterized by intra- and intermolecular
hydrogen bonds while weaker intermolecular hydrogen bonds (O···H−C) exist between the sheets. A
topological analysis of the electron density of genistein was then completed to characterize all covalent
bonds, three O···H−O and four O···H−C intermolecular hydrogen bonds. Two O···H−O hydrogen bonds
are incipient (partially covalent) type bonds, while the other O···H−O hydrogen bond and O···H−C hydrogen
bonds are of the pure closed-shell interaction type. In addition, two intermolecular H···H interactions have
also been characterized from the topology of the electron density. The binding of genistein to the estrogen
receptor is discussed in terms of the electrostatic potential derived from the electron density distribution.