Tautomerism and antioxidant activity of some 4-acylpyrazolone-based Schiff bases: a theoretical study

4-Acylpyrazolone Schiff bases display antimicrobial, antiprion, antioxidant, and other biological activities. They are also used as ligands and some of their complexes possess photoluminescence and anticancer properties. These Schiff bases may exist in four tautomeric forms that correspond to H at the C (imine-one(I)), N (imine-one(II)), and O (imine-ol) atoms of the pyrazolone ring or at the azomethine N atom (amine-one). While crystal structures show the amine-one form, the identity of the tautomeric form in solution and the structure–antioxidant activity relationship of these compounds are not clear. We perform quantum mechanical investigations on nine 4-acylpyrazolone-based Schiff bases at the B3LYP/6-311++G(d,p) level of theory in the gas phase and in chloroform, dimethyl sulfoxide, and water using the polarizable continuum model (PCM). Results show that the imine-ol, imine-one(I), and imine-one(II) isomers are, in respective, 6.5–8.0, 17–20, and 19–23 kcal mol(−1) less stable than the amine-one form and that solvents further stabilize the later form. The energy barrier for imine-ol to amine-one conversion is only 0–1 kcal mol(−1), showing that formation of the latter form is both kinetically and thermodynamically favorable. NMR calculations show that H in the amine-one and imine-ol forms appears at δ = 11.9–12.9 and 14.0–15.7 ppm, respectively, revealing that the experimentally reported (1)H NMR spectra of these compounds are due to the amine-one tautomeric form. The structure–antioxidant activity relationship is investigated and structural modifications that increase the antioxidant activity are discussed. Calculations using the PCM show that the vertical ionization potential (IPV) is inversely proportional with the ferric reducing antioxidant power (FRAP) of these compounds. IPV thus presents a valuable tool for predicting the FRAP.