Novel lithium ionic cocrystals with benzoic acid derivatives and L-proline: Synthesis, X-ray structures, IR spectrums, DSC analysis, and water solubility

Lithium therapy has been employed in the treatment of mental disorders for decades, while lithium cocrystals have garnered growing attention in recent years. However, research on lithium ionic cocrystals (ICCs) remains limited, and more research is needed for their structure diversities and interaction studies. Given this background, we synthesized six lithium ICCs with L-proline and benzoic acid derivatives, each substituted with different functional groups (-OH, -SH, -CH3, -OCH3, -SCH3) as co-formers. Their crystal structures were initially determined using single-crystal X-ray diffraction (SCXRD) and subsequently evaluated through infrared spectroscopy (IR), differential scanning calorimetry (DSC), and water solubility testing. Notably, we observed significant variations in the crystal packing, interaction mode, and physicochemical properties of the prepared ICCs, particularly in comparison between oxygen and sulfur substitution. IR spectra revealed signal shifts and intensity changes consistent with lithium coordination and other weak interactions involved. Moreover, all ICCs exhibited markedly enhanced thermal stabilities and water solubilities. In conclusion, our study not only yielded novel lithium ICCs but also provided valuable insights for the preparation of ICCs based on similar pharmacological templates.