17α-Estradiol·1/2 H₂O: Super-Structural Ordering, Electronic Properties, Chemical Bonding, and Biological Activity in Comparison with Other Estrogens

The biological function of steroidal estrogens is related to their electronic properties. An experimental charge density study has been carried out on 17α-estradiol and compared to similar studies on more potent estrogens. High accuracy X-ray data were measured with a Rigaku rotating anode diffractometer equipped with an R-Axis Rapid curved image plate detector at 20 K. The total electron density in the 17α-estradiol·1/2 H₂O crystal was modeled using the Hansen−Coppens multipole model. Topological analysis of the electron density based on Bader’s QTAIM theory was performed. The crystal structure, chemical bonding, and molecular properties, including the electrostatic potential (ESP), are reported and discussed. Observed disordering of hydroxyl and water hydrogen atom positions are interpreted as a superstructural ordering in a lower symmetry space group. The ESP’s for the resulting four conformers are compared with each other and with that of 17β-estradiol. The relative binding affinities are discussed in terms of the observed potentials.