Searching for Suitable Kojic Acid Coformers: From Cocrystals and Salt to Eutectics

Abstract

The possibility of obtaining cocrystals of kojic acid with organic coformers has been investigated by both computational and experimental approaches. Cocrystallization attempts have been carried out with about 50 coformers, in different stoichiometric ratios, by solution, slurry, and mechanochemical methods. Cocrystals were obtained with 3-hydroxybenzoic acid, imidazole, 4-pyridone, DABCO, and urotropine, while piperazine yielded a salt with the kojiate anion; cocrystallization with theophylline and 4-aminopyridine resulted in stoichiometric crystalline complexes that could not be described with certainty as cocrystals or salts. In the cases of panthenol, nicotinamide, urea, and salicylic acid the eutectic systems with kojic acid were investigated via differential scanning calorimetry. In all other preparations the resulting materials were constituted of a mixture of the reactants. All compounds were investigated by powder X-ray diffraction; the five cocrystals and the salt were fully characterized via single crystal X-ray diffraction. The stability of the cocrystals and the intermolecular interactions in all characterized compounds have been investigated by computational methods based on the electronic structure and pairwise energy calculations, respectively.

Mechanochemical Synthesis of New Praziquantel Cocrystals: Solid-State Characterization and Solubility

“…The melting of the cocrystal at lower temperatures compared to the pure components (PZQ and SUB) can be explained by the fact that the crystal lattice and the Gibbs energy of the cocrystal are lower than those of the individual components. The decrease in the melting point and enthalpy of fusion in the cocrystal compared to praziquantel alone indicates a decrease in the thermodynamic stability − and implicitly a higher solubility . From the comparison of the TG curve of the cocrystal PZQ·SUB (Figure b) with the TG curves of the initial ingredients, it was observed that the decomposition of the cocrystal occurs more slowly compared to the initial ingredients, and the mass loss is lower.…”

Insights into the binding mechanism of 2,5‐substituted 4‐pyrone derivatives as therapeutic agents for fused dimeric interactions: A computational study using QTAIM, dynamics and docking simulations of protein–ligand complexes

“…The molecular structure of 5H2HM4HP was examined using P1 point group symmetry and the resulting Figures 1 and 2 showcase the optimized geometry. Crystal dimensions, a = 147.515 Å, b = 102.166 Å, c = 60.572 Å; Angles between cell axes: α = 90°, β = 114.16°, γ = 90° and Volume (V) = 1.0000 (16) Å 3 [8]. In the study, theoretical bond lengths for asymmetry units (C‐6), (O‐4) and (H‐6) were found in the range 1.353–1.498 Å, 0.965–1.431 and 0.965–1.096 (in Å) at B3LYP/6‐311++G(d,p) method.…”

“…It has been shown to provide reliable results for a wide range of molecular systems and electronic states. This choice of functional and basis set has been extensively validated and used in similar studies in the literature [7,8], balancing computational efficiency and accuracy in predicting molecular properties [9].…”