Synthesis, molecular docking, drug-likeness analysis, and ADMET prediction of nickel and zinc tetraphenyl-porphyrin complexes as possible antioxidant agents

Nickel tetraphenyl-porphyrin (NiTPPH₂) and zinc tetra(4-methophenyl)-porphyrin (ZnTPPH₂(p-methyl)) were successfully synthesized and characterized using ¹H NMR spectroscopy. Their antioxidant activities and interactions with the superoxide anion radical ($O_2^{{•}^{\_}}$) were evaluated using cyclic voltammetry. Remarkably, NiTPPH₂ displayed superior antioxidant activity with an IC₅₀ value of 54.57 μg mL⁻¹, significantly outperforming α-tocopherol (IC₅₀ = 353.27 μg mL⁻¹), indicating its potential as a potent antioxidant. Binding free energy calculations demonstrated that electrostatic interactions predominantly govern the binding, with values of −23.47 kJ mol⁻¹ for NiTPPH₂ and −22.50 kJ mol⁻¹ for ZnTPPH₂(p-methyl). These values suggest robust binding affinities with $O_2^{{•}^{\_}}$. Quantum chemical parameters, obtained through density functional theory (DFT), showed a strong correlation with experimental results, validating the computational approach. Additionally, ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) and drug-likeness assessments, alongside molecular docking studies, highlighted favorable pharmacokinetic profiles and binding affinities. These findings underscore the potential of NiTPPH₂ and ZnTPPH₂(p-methyl) as promising candidates for antioxidant therapy, exhibiting drug-like properties and favorable pharmacokinetics. This research advances the understanding of these porphyrin derivatives and their application in the development of novel antioxidant therapeutics.