Insights into Intermolecular Interactions of Spironolactone Solvates

Abstract

To gain insights into the effect of weak interactions in solvate formation and structure−property correlation, experimental (thermal and structural analysis) and computational (lattice and pairwise energy calculations) studies were undertaken to relate intermolecular interactions to packing arrangements, formation mechanism, stability, and the desolvation process of spironolactone (SPI) solvates. Herein, four novel solvates were found, and the crystal structures of five solvates (formic acid, acetic acid, benzene, toluene, and acetonitrile) were resolved for the first time. Structural similarity and diversity of SPI forms are apparent according to the crystal structures, where the strongest interaction is the stacking of the steroid ring system via van der Waals forces. Although the solvent molecules are located in channels (acetonitrile molecules in isolated sites), they form hydrogen bonds and/or dispersion interactions with SPI frameworks. These findings can rationalize the relatively superior stability of SPI solvates. Both increased packing coefficient and additional SPI•••solvent interactions are the important driving forces for solvate formation, especially for the van der Waals force controlled solvates. Besides, the thermodynamic stability determines the desolvation of SPI solvates to form II, while the desolvation pattern between formic acid solvate to form I is guided by the isostructural pairs.

Insights Into the Properties of Amygdalin Solvatomorphs: X-ray Structures, Intermolecular Interactions, and Transformations

“…The transformation relationship of different AMY forms is very significant in the manufacturing process. 38 AMY has a high propensity to form solvatomorphs, and the recrystallized conditions in most solvents need to be controlled carefully when the no-solvent form is the desired product. This also suggests that if new alcohols, such as n-octanol, are used, the corresponding AMY alcohol dihydrates may also be formed.…”

Structural Insights into the Highly Solvating System of Axitinib via Binary and Ternary Solvates

“…In types 1 and 2 isostructural solvates, the solvent molecules were embedded in the channel by weak interactions. Moreover, although packing efficiency is often used to rationalize the formation of solvates and cocrystals, 17,18,41 the packing index of the seven solvates were all lower than those of the raw materials (form IV or XLI), so the improvement of stacking efficiency is not a necessary condition for the formation of solvates. Nevertheless, the lattice energy of solvates was all higher than that of solventfree polymorph (Table S2).…”

“…Although, as it claims, thermal stability is related to the normal boiling point of the solvent, it can only be true when the solvent molecule binds weakly to the host substance and is located in an open void. In other cases, , the thermal stability of the solvates obtained from the experiment does not match the order of the boiling point of the solvent, and the stability of the solvent should strongly depend on the presence of different solvent–host intermolecular interactions and steric hindrance of the solvent molecule in the host structure . The ambiguity between isostructuralism and formation mechanisms, more exploration, and in-depth analysis are necessary.…”

Cocrystal engineering strategy for sustained release and leaching reduction of herbicides: a case study of metamitron

“…The process of cocrystal solubility in a solution is primarily separated into two stages: the first stage involves the destruction of the crystal lattice (lattice energy, Δ G lattice ), and the second stage involves the solvation of solute molecules (solvation free energy, Δ G solvation ). 47 The two main factors associated with the overall free energy of the solution are given by:Δ G solution = Δ G lattice + Δ G solvation where Δ G solution represents the Gibbs energy change associated with the solubilization process, including lattice destruction and solvation.…”

“…The process of cocrystal solubility in a solution is primarily separated into two stages: the first stage involves the destruction of the crystal lattice (lattice energy, ΔG lattice ), and the second stage involves the solvation of solute molecules (solvation free energy, ΔG solvation ). 47 The two main factors associated with the overall free energy of the solution are given by:…”