Antioxidant potential of porphyrin derivatives revealed by electrochemical, spectroscopic, and computational studies

Oxidative stress plays a central role in degenerative and inflammatory diseases, making the development of potent antioxidants a priority. Porphyrin-based derivatives are promising due to their redox tunability and structural stability. Two porphyrin derivatives, TbiPPH2 and ToMePPH2, were synthesized and characterized, their DPPH radical scavenging activities were subsequently assessed via both UV–Vis and CV techniques. Computational studies were then performed to evaluate drug-likeness, ADMET properties, molecular docking against Keap1, molecular dynamics (MD) simulations, and MM-GBSA binding free energy calculations. Both TbiPPH2 and ToMePPH2 demonstrated notable antioxidant activity, with EC50 values of 46.707 and 63.346 μM, respectively, as determined by cyclic voltammetry and confirmed by UV–Vis spectrophotometry. Diffusion coefficient values derived from CV indicated efficient electron transfer kinetics. In silico analyses revealed favorable drug-likeness and ADMET profiles. Molecular docking against Keap1 yielded binding free energies of 􀀀 8.16 and 􀀀 7.23 kcal/mol for TbiPPH2 and ToMePPH2, respectively, which were further supported by molecular dynamics simulations and MM-GBSA calculations, confirming stable and energetically favorable complexes. TbiPPH2 and ToMePPH2 demonstrate potent antioxidant capacity, stable Keap1 binding, and favorable predicted ADMET characteristics, nevertheless, further in vivo and pharmacological studies are required to validate their antioxidant efficacy and safety profiles.