Interaction of amantadine with squaric acid and water; Crystal structure, spectroscopic and DFT analysis

A novel salt, amantadinium hydrogen squarate hydrate (1), has been synthesized and characterized by single-crystal X-ray diffraction (SXRD) and Fourier-transform infrared (FTIR) spectroscopy. The crystals of 1 crystallize in the centrosymmetric triclinic space group , with the asymmetric unit comprising two independent amantadinium cations, two hydrogen squarate anions, and two water molecules. The hydrogen squarate anions form an infinite zigzag α-chain via short O−H···O hydrogen bonds of 2.521(2) Å and 2.520(2) Å. The FTIR spectrum exhibits a band at 3035 cm-1, corresponding to the stretching vibration of the N+−H···O- interactions, and a broad absorption centered at 1316 cm-1, attributed to O−H stretching vibrations associated with the short hydrogen bonds between hydrogen squarate anions. The structural features in the solid state were further investigated using density functional theory (DFT) calculations at the APF-D/6–311++G(d,p) level, complemented by the Quantum Theory of Atoms in Molecules (QTAIM) approach. A comparison was made between the experimental and computed infrared spectra. Additionally, the thermal stability of 1 was assessed using thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). The biological activity of 1, as well as its components – amantadine (AMD) and squaric acid (H2SQ) – was evaluated through their interactions with selected strains of bacteria and mold fungi.