Two Faces of Water in the Formation and Stabilization of Multicomponent Crystals of Zwitterionic Drug-Like Compounds

• Main Authors: Artem O. Surov, Nikita A. Vasilev, Andrei V. Churakov, Olga D. Parashchuk, Sergei V. Artobolevskii, Oleg A. Alatortsev, Denis E. Makhrov, Mikhail V. Vener
• Format: Article
• Language: English
• Published: MDPI AG 2021-03-01
• Series: Symmetry
• Subjects: 2-aminonicotinic acid; maleic and fumaric acids; intra- and inter-molecular hydrogen bonds; structure-directing role of water; periodic (solid-state) DFT computations; low-frequency Raman spectrum
• Online Access: https://www.mdpi.com/2073-8994/13/3/425

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.