Journal of the American Chemical Society, Vol.129, No.48, 15013-15021, 2007
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 center dot center dot center dot H-G) exist between the sheets. A topological analysis of the electron density of genistein was then completed to characterize all covalent bonds, three O center dot center dot center dot H-O and four O center dot center dot center dot H-C intermolecular hydrogen bonds. Two O center dot center dot center dot H-O hydrogen bonds are incipient (partially covalent) type bonds, while the other O center dot center dot center dot H-O hydrogen bond and O center dot center dot center dot H-C hydrogen bonds are of the pure closed-shell interaction type. In addition, two intermolecular H center dot center dot center dot 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.