Structure and Thermal Stability of Two Estetrol Solvates

Two solvates of estetrol have been isolated and characterized by SCXRD and PXRD as well as by thermal analyses, morphology and spectroscopy. Estetrol monohydrate (Estetrol.H2O, S.G. P1, Z = 12) contains 12 molecules in its asymmetric unit with very subtle conformational differences with one another but reveals an intricate network made of intermolecular H-bonds established with the neighbour estetrol molecules and with crystallization water. Each molecule of estetrol methanol hemisolvate (Estetrol.0.5CH(3)OH, S.G. C2, Z = 4) establishes six O-H horizontal ellipsis O bonds with six different neighbours and additional H-bonds with methanol. In both structures, estetrol molecules are organized in a head-to-tail arrangement that favours the formation of O-H horizontal ellipsis O interactions. The increased thermal stability of Estetrol.0.5CH3OH crystals with respect to Estetrol.H2O can be correlated to the strengthened network of H-bonds.

Automated summary

Two solvates of estetrol, Estetrol.H2O and Estetrol.0.5CH(3)OH, were isolated and characterized using SCXRD, PXRD, thermal analyses, morphology, and spectroscopy. The structures of both solvates show intricate networks of intermolecular hydrogen bonds, with Estetrol.H2O containing 12 molecules in its asymmetric unit and Estetrol.0.5CH(3)OH establishing six O-H...O bonds with different neighbors and additional H-bonds with methanol. The higher thermal stability of Estetrol.0.5CH3OH crystals compared to Estetrol.H2O crystals can be attributed to the strengthened network of hydrogen bonds.