| Abstract |
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 beta-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 p...p 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. |
