Unconventional Dehydration Pathway of an Elusive Organic Sodium Salt Hydrate

The development of organic metal salt hydrates as supramolecular crystalline materials requires a fundamental understanding of how molecular assembly, involving diverse types of lattice-bound water, can influence both microstructure and macroscopic properties. Herein, we demonstrate electron diffraction as a powerful tool for capturing the structure of an elusive nanosized organic sodium salt hydrate with variable water content, using the drug compound risedronate sodium (RS) as a case study. Within the complex structure of the 2.5-hydrate featuring ion-coordinated, channel, and isolated-site water molecules, we found that dehydration unexpectedly occurs at ion-associated water molecules rather than at hydrogen-bonded ones. Combining electron diffraction, synchrotron powder X-ray diffraction, and noncovalent interaction analysis based on density-functional theory, we elucidate the underlying transition mechanism resulting from motions of lattice water and conclude principles of water site removal. Our findings reveal that the fast interconversion between 2.5-hydrate and a nonstoichiometric hydrate arises from their dynamic, reversible noncovalent interactions related to water molecules and a flexible sodium ion-coordination network. This study provides an example of applying electron diffraction to elucidate the structure of short-lived, nonstoichiometric organic metal salt hydrates and sheds light on how the hydrate structures with different water–ion coordination impact the supramolecular organization and dehydration pathways.