Solid-State Characterization and Role of Solvent Molecules on the Crystal Structure, Packing, and Physiochemical Properties of Different Quercetin Solvates

In this work, a novel quercetin and dimethyl sulfoxide (DMSO) solvate (QDMSO) crystal structure was grown from a mixture of DMSO and water as solvent. Quercetin is a naturally occurring bioflavonoid widely used in the nutraceutical industry due to its many health benefits. Understanding quercetin solvates formation is essential for the design of novel particulate products with tailored quality attributes, including solubility, thermal resistance, and bioavailability. Here, the physiochemical properties and phase transitions of QDMSO were characterized by a wide range of experimental techniques, and the crystal structure, molecular packing, and intermolecular interactions (synthons) within the crystal lattice were modeled. Modeling and experimental results were compared to those of other known quercetin crystal structures, an anhydrous, a monohydrate, and a dihydrate form, to elucidate the role of the solvent molecules on the molecular packing and intermolecular interactions and, ultimately, on the physiochemical properties of each crystal form. It was found that in QDMSO, hydrogen bonds and dipole–dipole interactions had a greater contribution to the total lattice energy, and quercetin–solvent hydrogen bonds were stronger in energy compared to those of the other quercetin structures. These findings were used to explain the superior thermal stability of the QDMSO structure as well as its moisture-dependent behavior. This work demonstrates a coupled modeling and experimental methodology that relates intermolecular interactions and molecular packing in different solvated forms to physiochemical properties and can help in a better prediction and design of particulate products via the rational choice of the solid form.