Exploration of the Solid Forms of Cepharanthine: Crystal Structure and Phase Transformation

Recently, researchers found the abilities of cepharanthine (CEP) to prevent and treat coronavirus. However, the study about CEP solid forms has been rarely reported. In this study, the crystal structure of CEP form I was first solved, and eight solvates were screened and discovered based on the conductor-like screening model for real solvents. The crystal structures of five solvates of CEP with methanol (S_MeOH), acetonitrile (S_ACN), methyl acetate (S_MA), ethyl acetate (S_EA), and butyl acetate (S_BA) were solved. The results showed that five solvates belonged to isolated-site solvates. Hydrogen bonding between the solvent molecule and the active pharmaceutical ingredient molecule was present only in S_MeOH. The remaining four solvates formed C-H···O weak hydrogen bonds and C-H···π interactions between the host and guest. The mechanism of solvate formation was explained by calculating the packing coefficients, and it was proved that the introduction of solvent molecules mainly made the crystal structure packed more effectively. In addition, the desolvation of the five solvates were studied and found that the desolvation of S_MeOH followed a cooperative mechanism, while S_ACN, S_MA, S_EA, and S_BA conformed to a destruction-collapse mechanism.