In vitro and in silico studies of radical scavenging activity of salicylaldehyde benzoylhydrazones

Hydrazones are key compounds for drug design and popular building blocks in the development of functional materials because of their simple structure, straightforward synthesis, hydrolytic stability, tendency toward crystallinity and tunable properties, etc. Hydrazones have been under study for a long time, but many of their electronic and structural properties (that can be attributed to the basic system structure) remain unexplored. In this paper the effect of substitution is studied for a set of selected aroylhydrazones – derivatives of the active chelator salicylaldehyde benzoyl hydrazone (SBH). The molecular structure of the compounds in nonpolar and polar media was characterized by DFT computations and vibrational (ATR-FTIR and Raman) spectroscopy. The radical scavenging ability of the compounds was tested towards stable free radicals as well as for inhibiting the iron induced oxidative stress in a lecithin containing model system. The possible mechanisms of antioxidant action were evaluated by DFT calculations in polar and nonpolar media. The most reactive sites for hydrogen atom abstraction and proton transfer were determined based on the calculated enthalpies required for the formation of hydroxyl and amide radicals and ionic species. The structural parameters and thermodynamic data for the studied compounds were correlated with the observed effects in the in vitro model systems in order to rationalize the influence of the nature and position of the substituent in the phenyl ring on the antioxidant properties.