Bader analysis

In this work, three new pharmaceutical salts of fenbendazole (FNB), a benzimidazole-based anthelmintic drug, with sulfonic acids have been obtained and thoroughly investigated by different analytical techniques, including thermal methods, infrared/Raman spectroscopy, and theoretical methods (periodic DFT computations and Bader analyses of the crystalline electronic density). Single-crystal and high-resolution synchrotron powder X-ray diffraction data for the first time made it possible to determine the crystal structures of mesylate and tosylate salts of the drug, which were further validated by dispersion-corrected density functional theory calculations. All the solid forms were stabilized by a robust R 2 2 (8) supramolecular motif formed by relatively strong N−H•••O hydrogen bonds. In the monohydrate of FNB tosylate, a considerable gain in the stabilization energy was due to the intermolecular interactions generated by the water molecules. A careful examination of the solubility−pH profile of the FNB salts revealed that, despite being thermodynamically unstable within the physiologically relevant pH range, the new solid forms demonstrated superior dissolution performance in terms of both the apparent solubility and the release rate in comparison to the parent drug. Since FNB has also been reported to possess anticancer activity, improving the drug's poor physicochemical properties through salt formation with the selected sulfonic acids is expected to promote further investigations toward repurposing of this potent compound.

Two new hydrated multicomponent crystals of zwitterionic 2-aminonicotinic acid with maleic and fumaric acids have been obtained and thoroughly characterized by a variety of experimental (X-ray analysis and terahertz Raman spectroscopy) and theoretical periodic density functional theory calculations, followed by Bader analysis of the crystalline electron density) techniques. It has been found that the Raman-active band in the region of 300 cm−1 is due to the vibrations of the intramolecular O-H...O bond in the maleate anion. The energy/enthalpy of the intermolecular hydrogen bonds was estimated by several empirical approaches. An analysis of the interaction networks reflects the structure-directing role of the water molecule in the examined multicomponent crystals. A general scheme has been proposed to explain the proton transfer between the components during the formation of multicomponent crystals in water. Water molecules were found to play the key role in this process, forming a ...

Two new hydrated multicomponent crystals of zwitterionic 2-aminonicotinic acid with maleic and fumaric acids have been obtained and thoroughly characterized by a variety of experimental (X-ray analysis and terahertz Raman spectroscopy) and theoretical periodic density functional theory calculations, followed by Bader analysis of the crystalline electron density) techniques. It has been found that the Raman-active band in the region of 300 cm−1 is due to the vibrations of the intramolecular O-H...O bond in the maleate anion. The energy/enthalpy of the intermolecular hydrogen bonds was estimated by several empirical approaches. An analysis of the interaction networks
reflects the structure-directing role of the water molecule in the examined multicomponent crystals. A general scheme has been proposed to explain the proton transfer between the components during the formation of multicomponent crystals in water. Water molecules were found to play the key role in this process, forming a “water wire” between the COOH group of the dicarboxylic acid and the COO–
group of the zwitterion and the rendering crystal lattice of the considered multicomponent crystals.