Crystal Structure, Hirshfeld Surface Analysis, and Biological Activities of Schiff-Base Derivatives of 4-Aminoantipyrine

Eight Schiff bases, synthesized by the reaction of 4-aminoantipyrine with different cinnamaldehydes, were studied in the solid state by using vibrational spectroscopy (IR) and X-ray diffraction techniques. The analysis was extended to the solution phase through ultraviolet-vis, fluorescence spectroscopy, and cyclic voltammetry. Finally, the crystal structures of four compounds (, , , and ) were determined and studied. In addition to the experimental study, theoretical calculations using the semiempirical method PM6/ZDO were performed to understand better the compound's molecular properties, UV-vis, and infrared spectra. The primary difference is the angular conformation of the terminal phenyl rings around the corresponding linking C-N and C-C σ-bonds. Furthermore, as a result of extended bonding, the > C=N- azomethine group-containing C-N=(CH)-(CR)=(CH)-C chain (with R=H for , , and , and R=CH for ) is planar, nearly coplanar, with the mean plane of the pyrazole ring. Hirshfeld surface (HS) analysis was used to investigate the crystal packing and intermolecular interactions, which revealed that intermolecular C-H···O and C-H···N hydrogen bonds, π···π stacking, and C-H···π and C=O···π interactions stabilize the compounds. The energy contributions to the lattice energies of potential hydrogen bonds were primarily dispersive and repulsive. All derivatives were tested on LPS-stimulated mouse macrophages to assess their ability to suppress the LPS-induced inflammatory responses. Only a slight reduction in the level of NO production was found in activated macrophages treated with . Additionally, the derivatives were tested for antimicrobial activity against several clinical bacteria and fungi strains, including three biofilm-forming microorganisms. Nevertheless, only Schiff base showed interesting antibacterial activities with minimum inhibitory concentration (MIC) values as low as 15.6 μM against . On the other hand, Schiff base and, to a lesser extent, and showed antifungal activity against clinical isolates of . The lowest MIC value was for against (15.6 μM). It is interesting to note that the same Schiff bases exhibit the highest activity in both biological evaluations.