New bis(isatins-thio/carbohydrazones) based on Schiff bases were prepared from terephthalaldehyde biscarbohydrazone and 5-substituted isatins in the presence of a drop of sulfuric acid under reflux in ethanol. Terephthalaldehyde bis(thio/carbohydrazone) was synthesized by the reaction of (thio)/carbohydrazide and terephthalaldehyde in the presence of a few drops of acetic acid under reflux in ethanol. The structures of these synthesized compounds were determined using IR, 1H NMR, and 13C NMR spectroscopy and elemental analysis. The in vitro antioxidant activity of all the compounds was determined by the 1,1-diphenyl-2-picryl hydrazyl (DPPH.) free radical scavenging method. Compound 2 showed the best antioxidant activity.

Isatin-derived Schiff bases are the subject of many studies, finding wide application areas in polymer technology, pharmaceutical industry, and medicine. In this study, a series of new Schiff bases were prepared from monothiocarbohydrazones based on isatins with different substituents (5-F, 5-Br, 5-I, and 5-MeO). The chemical structures of the synthesized compounds were determined using ¹H NMR, ¹³C NMR, FTIR spectroscopic techniques, and elemental analysis. Antioxidant activity determinations of 23 compounds were performed using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical quenching method. The highest percent inhibition value at 10 µM concentration was shown by compound number 22, 5-bromoisatin Schiff base containing 3-methoxy-4-hydroxy group. Compound 17, a 5-iodoisatin Schiff base containing 3-methoxy-4-hydroxy group, showed the highest antioxidant activity with an IC₅₀ value of 9.76 ± 0.03 µM. In addition to the theoretical analysis of the compounds, both their spectroscopic and antioxidant properties were investigated. The ground-state geometries and some chemical reactivity parameters of the compounds were calculated using the B3LYP/6-311 + + G(2d,2p) approach. Besides intramolecular interactions, substituent effects, and some QTAIM parameters, the calculations were also performed to study the electronic properties of reactive N/O–H bonds and were used to interpret the experimental results. The effects of the electronic parameters and intramolecular interactions of reactive N/O–H bonds on the antioxidant properties of the compounds were investigated. Additionally, the relationships of DPPH reactions with delocalization indices of N/O-H bonds and the pattern of SET/HAT mechanisms with electronic variables were analyzed. Examination of electron and hydrogen atom transfer mechanisms has shown the dominance of electron transfer, supported by the correlation coefficients between IC₅₀ values and SET reaction energies.

GRAPHICAL ABSTRACT 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), 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.