Experimental Charge Density Study of Estrogens: 17β-Estradiol·Urea

To relate the molecular electrostatic potential to the biological activities of estrogens, a comparative charge
density study of different derivatives has been initiated. The second completed charge density analysis of this
series for 17β-estradiol·urea is presented here. This is a large organic system with 52 atoms in a
noncentrosymmetric space group, therefore special tools such as an optimal coordinate system and slow,
initially constrained refinement have been used to accomplish this study. Our results for the urea molecule
reasonably agree with previous experimental and theoretical results. In the 17β-estradiol molecule, the oxygen
atoms appear to be close to sp3 in shape, exhibiting two consistent, distinct lone pairs despite different chemical
environments. No significant interaction of the hydroxyl group oxygen with the π orbitals of the aromatic
ring is observed. Analysis of the electrostatic potential revealed that the negative potential in the lone pair
region of the two oxygen atoms is quite different. The topological analysis of the electron density has been
performed, and the atomic charges have been estimated.