Azine-hydrazone Tautomerism of Thiazolylazo Pyridine Compound: Synthesis, Structural Determination, and Biological Activities

Abstract

The azine-hydrazone tautomeric compound 1, (Z)-3-(2-(thiazol-2-yl)hydrazineylidene)pyridine-2,6(1H,3H)-dione, was synthesized by diazotization and coupling reactions under low temperature. Its needle-like crystal structure was analyzed by single-crystal X-ray diffraction. The molecular structure of compound 1 in solid state obtained from single crystal analysis was in the different isomeric form compared to the structure in the solution determined by NMR. Based on the DFT quantum calculations, the result suggested that the most stable form of compound 1 was in the hydrazone-keto-keto (HYD-1) form with the lowest total energy. However, HYD-1 can tautomerize to the azine form (AZINE-1) in the solution as observed by the NMR analysis. The equilibrium of these two isomeric forms was also studied by UV-vis spectroscopy in different solvents and pH. The absorption spectra displayed the bathochromic shift of compound 1 with increasing pH and the percentage of two isomeric forms was equal at pH 5.8. Moreover, the biological activity of the compound 1 was studied by using one of these pepsin and papain assays. The results exhibited that the IC50 of compound 1 was found to be 29.83 ± 0.02 µM and 78.18 ± 0.06 µM, respectively.