Solvent-Mediated Crystal Shape Transformation of 7-Aminocephalosporanic Acid at the Interface

Abstract The crystal morphology is a crucial attribute indicator and directly affects downstream processing, which is basically modified by solvents. However, a comprehensive mechanistic understanding of solvent-mediated crystal shape transformation at solvent-crystal face interfaces remains unsolved. This work studied the solvent-mediated crystal shape transformation mechanism at the solvent-crystal face interface from the intrinsic crystal structure and solvent environment using 7-aminocephalosporanic acid (7-ACA) whose crystal structure remained the same during the studied solvents. Three distinct crystal shapes were obtained from three solvents and predicted by the modified attachment energy model. The 7-ACA crystal was constructed by weak contacts and easily affected by solvents according to the molecular packing structure, Hirshfeld surface, and independent gradient model based on Hirshfeld partition. Besides, solvent effects on the crystal growth at solvent-crystal face interfaces were elucidated at the molecular level based on mean-square displacement, diffusion coefficient, radial distribution function, and adsorption energy of solvent molecules onto various crystal faces. Results exposed different solvent mobility and interaction on the crystal surface induced crystal face anisotropic growth and modified the crystal shape. Finally, a solvent-mediated crystal shape transformation mechanism was proposed to reveal the selective solvent effects on the crystal growth at the interface.