Structural and Computational Study of 4 New Solvatomorphs of Betulin: A Combined X-Ray, Hirshfeld Surface, and Thermal Analysis

Abstract

Four new solvatomorphs of betulin were reported and characterized by X-ray diffractometry as well as thermal and vibrational spectroscopic analyses. Single-crystal X-ray diffraction was used to analyze the X-ray structures of the compounds and confirmed the stoichiometric ratio between the host and guest molecules from thermal data. Results indicated that solvatomorphism occurred in several betulin solvates. Changes in intermolecular arrangements, stoichiometry, and hydrogen-bonding interactions of solvatomorphs were due to solvent incorporation to solvates. Hirshfeld surface analyses, especially dnorm surface and fingerprint plots, were used to determine intermolecular interactions in the crystal network. Solvent molecules played an important role in the construction of a 3D architecture. The stabilities of these solvates were evaluated by thermal analyses. Nonisothermal kinetic analysis was used to explain the kinetics of solid–solid phase transition (desolvation) of betulin solvates. The apparent activation energies were evaluated using Kissinger and Ozawa methods. Moreover, phase transitions were visually investigated by hot-stage microscopic analysis.