Structure, tautomerism, and radical scavenging activity of Schiff bases and hydrazones of gossypol

Abstract

The structure, tautomerism, and intramolecular hydrogen bonds of seven imine derivatives of natural polyphenol gossypol were studied in solutions, the solid state, and the gas phase by ¹H and ¹³C NMR, FT-IR spectroscopy and quantum chemical calculations. It was shown that gossypol Schiff bases exist in the dienamine tautomeric form, while gossypol hydrazones in the diimine form. Key chemical shifts in the ¹H and ¹³C NMR spectra, which indicate the existence of the dienamine or diimine tautomer in solutions, were found. It was shown that the dienamine tautomeric form is energetically favorable for the studied Schiff bases (gives 4 phenolic hydroxyl groups) in the gas phase, while the diimine tautomeric form is favorable for the hydrazones (gives 6 phenolic hydroxyl groups). All hydroxyl groups of the gossypol fragment of the compounds both in the dienamine and diimine tautomeric forms participate in the formation of intramolecular hydrogen bonds of different strengths. Using hydrogen bond length the energies of all intramolecular hydrogen bonds of the studied gossypol imine derivatives in the gas phase were assessed. The radical scavenging activity of the studied gossypol imine derivatives was evaluated in the reaction with DPPH in ethanol. All studied compounds were shown to be effective radical scavengers comparable to highly effective naturally occurring antioxidants. Some of them are 4 times more effective than caffeic acid in their radical scavenging properties. The modification of gossypol by introducing amines and hydrazines containing groups capable of reacting with free radicals allows obtaining promising and highly effective radical scavenging agents.