Synthesis of new 5-iodoisatin derivatives: Predicting antioxidant inhibition activity with DFT studies

New 5-iodoisatin-aryl/alkyl/thiosemicarbazones (1-8) were synthesized from various isocyanates and 5-iodoisatin, and their structures were validated by spectroscopic and elemental analysis. The in vitro antioxidant activity of these compounds was tested using the DPPH free radical trapping method, yielding IC50 values ranging from 14.11 to 20.48 mu M. DFT calculations were performed at the B3LYP/6-311++G(2d,2p) level of theory using the genecp approach with the def2-QZVPP basis set for the iodine atom. The intrinsic bond strength index (IBSI) values of the N-H bonds in the compounds, along with their density of state (DOS) properties and average local ionization energies (ALIE), were investigated. The influence of SET and HAT mechanisms in the reaction of compounds with DPPH was predicted based on the concentration of the compounds, and the possible effects of parameters that support the dominant characteristics in these reactions were investigated using computational data such as single electron transfer enthalpy (SETE) and bond dissociation energy (BDE). Furthermore, a function based on DFT data was proposed to compare the inhibition percentages of the compounds' reactions with DPPH to each other and to Trolox. Strong correlations were obtained suggesting that the inhibition effect of the compounds relative to Trolox could be estimated computationally with the function. The Pearson correlation coefficients between the experimental inhibition percentages of compounds and Trolox and the values predicted by the function at low concentrations of 1.25 and 2.50 mu M were calculated as 0.924 and 0.968, respectively. For higher concentrations in the range of 5.00-12.50 mu M, correlations ranging from 0.848 to 0.923 were obtained.