Influence of intermolecular interactions and crystal structure on desolvation mechanisms of solvates

Solvates are important forms of crystalline materials and their formation and desolvation would affect the quality of the final products. In this work, to better understand the desolvation mechanism of solvates and its effect on the properties of the final products, cefathiamidine was selected as the model compound to investigate the influence of intermolecular interactions and the crystal structure on the desolvation process. Three new solvates and one reported solvate of cefathiamidine, including acetonitrile solvate monohydrate S1, acetone solvate monohydrate S2, n-propanol solvate 1.5 hydrate S3 and isopropanol solvate S4, were obtained by solution crystallization and their structures were determined by single crystal X-ray diffraction. The results indicated that the cefathiamidine molecule is highly conformationally flexible and eight conformations were observed in these solvates. The different solvates exhibit different intermolecular interactions, packing patterns and crystal stabilities. Furthermore, the desolvation processes of the solvates were systematically investigated by various analytical techniques and were analyzed based on the intermolecular interactions, molecular networks, void types, proportion of voids and packing patterns. The results showed that the desolvation of solvates S1 and S2 followed a cooperative–reorganization mechanism while the desolvation of solvate S3 and solvate S4 followed a destruction–reconstruction mechanism and a destruction–collapse mechanism, respectively. Finally, the corresponding mechanisms of the different solvates were proposed.