Spectroscopic and theoretical study of the o-vanillin hydrazone of the mycobactericidal drug isoniazid

A complete and detailed study of the hydrazone obtained from condensation of antituberculous isoniazid (hydrazide of the isonicotinic acid, INH) and o-vanillin (2-hydroxy-3-methoxybenzaldehyde, o-HVa) is performed. It includes structural and spectroscopic analyses, comparing experimental and theoretical results. The compound was obtained as a chloride of the pyridinic salt (INHOVA+Cl−) but it will be referred as INHOVA for the sake of simplicity. The conformational space was searched and optimized geometries were determined both in gas phase and including solvent effects. Vibrational (IR and Raman), electronic and NMR spectra were registered and assigned with the help of computational methods based on the Density Functional Theory. Isoniazid hydrazones are good candidates for therapeutic agents against tuberculosis with conserved efficiency and lower toxicity and resistance than parent INH.

► Hydrazone (INHOVA) from condensation of isoniazid (INH) and o-vanillin (o-HVa).
► Solvent effects determine stable structure in solid-state.
► Vibrational and 1H, 13C NMR spectra assigned with help of calculated DFT data.
► UV–Vis spectrum dominated by o-HVa → o-HVa and o-HVa → INH transitions.