Experimental and theoretical investigation of antioxidant activity and capacity of thiosemicarbazones based on isatin derivatives

Abstract

The peroxidation of linoleic acid (LA) in the presence of copper (II) ions alone and with butylhydroxytoluene (BHT), gallic acid (GA), a BHT/GA pair, 5-methoxyisatin-3-(N-4-chlorophenyl) thiosemicarbazone (H₂5MI3ClPT), and 5-methoxyisatin-3-(N-phenyl) thiosemicarbazone (H₂5MI3PT) was investigated in aerated and incubated emulsions at 37°C and pH 7. Cu(II)-induced LA peroxidation followed pseudo-first-order kinetics with respect to the primary oxidation products (hydroperoxides), which were determined by the ferric thiocyanate (Fe(III)-SCN) method. It was observed that (H₂5MI3ClPT) and (H₂5MI3PT) showed antioxidant properties, but the percentage inhibition decreased as the concentration increased, contrary to the behavior of GA and BHT. In addition, they were investigated by the DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging method. The IC₅₀ values were 69.60, 11.87, 88.71, 73.62, and 430.11 µM for the standard antioxidants BHT, GA, H₂5MI3ClPT, H₂5MI3PT, and bis(isatin-3-(4-iodophenyl)thiosemicarbazonato) zinc(II) (BI3ITZn)<i>,</i> respectively. The bond dissociation enthalpy (BDE), adiabatic ionization potential (AIP), proton dissociation enthalpy (PDE), proton affinity (PA), electron transfer enthalpy (ETE), ΔH_acidity, ΔG_acidity descriptors and DPPH radical scavenging mechanisms of thiosemicarbazone were also determined with the B3LYP method. Furthermore, the energy values in the transition state form for the reactions of H₂5MI3PT and H₂5MI3ClPT with DPPH were calculated as 0.022278 and 0.021953 au, respectively.