Molecular Recognition of Steroid Hormones in the Solid State: Stark Differences in Cocrystallization of β‑Estradiol and Estrone

• Published in: Crystal growth & design Vol. 15; no. 3; pp. 1492 - 1501
• Main Authors: Ardila-Fierro, Karen J, André, Vânia, Tan, Davin, Duarte, M. Teresa, Lancaster, Robert W, Karamertzanis, Panagiotis G, Friščić, Tomislav
• Format: Journal Article
• Language: English
• Published: American Chemical Society 04.03.2015
• ISSN: 1528-7483; 1528-7505
• DOI: 10.1021/cg501865h

While the understanding of the supramolecular chemistry of steroidal hormones is largely based on receptor binding studies in vitro and in vivo, their solid-state molecular recognition properties remain unexplored. Here, we use mechanochemical cocrystallization and single crystal X-ray structure analysis to gain insight into the solid-state complexation of sex hormones with arenes, by systematic investigation of the ability of two important estrogens ß-estradiol (bes) and estrone (est) to form cocrystals with 1,2-dimethylnaphthalene, phenanthrene, anthracene, 9,10-anthraquinone, phenanthridine, benzo[h]quinoline, and perfluoronaphthalene. Cocrystallization of bes reveals the formation of a novel hydrogen-bonded lattice host, exhibiting rectangular channels occupied by arene guests. In striking contrast to bes, its 17-keto-analogue est did not yield cocrystals with any of the explored arenes except perfluoronaphthalene, revealing association via arene-perfluorarene π···π stacking. The results reveal previously unknown solid-state complexation behavior of important estrogen hormones, demonstrating how minor changes in the steroid structure, in particular switching from a 17-hydroxyl to a 17-keto group, can result in extraordinary changes to their solid-state self-assembly. In that respect, solid-state chemistry of steroids appears to mirror their important signaling role in biological systems, as very small modifications to the steroid structure lead to large changes in cocrystallization propensity.