Synthesis, Characterization, Crystal Structure, Hirshfeld Surface Analysis, and DFT Studies of an Isoniazid-Derived Schiff Base and Its Hybrid Salt

Abstract

The structural and electronic properties of new ionic compound 2-hydroxy-1-naphthaldehyde isonicotinoylhydrazone thiocyanate ([2-HNA/INH(SCN)]⁺), synthesized from isoniazid (INH), 2-hydroxy-1-naphthaldehyde and thiocyanate, are discussed using experimental and density functional theory approaches. The structure of the salt was elucidated using spectral analysis, single crystal X-ray diffraction analysis and conductivity measurements. Hirschfeld surface (HS) analysis, quantum theory of atoms in molecule (QTAIM), non-covalent interactions-reduced density graph (NCI-RDG) and intermolecular energies were combined to identify and characterize the non-covalent interactions (NCIs) that oriented and held the ions together in the crystal and rationalized using molecular electrostatic potential surface calculations. The kinetic stability and the chemical reactivity of the salt were analyzed using frontier molecular orbital distribution, global chemical descriptors and the molecular electrostatic potential map. Time dependent density functional theory (TD-DFT) was used to simulate the UV–Vis spectra of the salt in different solvents. The influence of cyclohexane, DMSO, ethanol and water on the calculated properties was also evaluated. A good correlation between experimental and theoretical data has been demonstrated by this study. The Schiff base and the salt were screened for their activity against five (5) reference bacteria strains and clinical isolates including Enterococcus faecium (EF), Escherichia coli (EC), Salmonella typhi (ST), Salmonella enterica (SE) and Staphylococcus aureus (SA), three (3) Candida species.

Graphical Abstract

Graphical Abstract