Abstract / Summary
Bisphenol (BP) analogues are widely used in plastics, epoxy resins, coatings, and flame-retardant materials as industrial alternatives to conventional BPs, yet their toxicological behavior remains insufficiently characterized. In this study, eight BP analogues, namely BPG, BPM, BPP, BPAP, BPC2, BPPH, TBBPA, and TBBPS, were systematically investigated using a combined quantum chemical and in silico toxicological approach. Density functional theory at the B3LYP/6–31+G(d,p) level was employed for geometry optimization and electronic property analysis, including HOMO-LUMO energies, hardness, softness, molecular electrostatic potential, FT-IR, and UV–vis characteristics. Molecular docking against the human estrogen-related receptor gamma ligand-binding domain (2E2R), 100 ns MD simulations, and ADMET/PASS prediction tools were further applied to assess binding behavior, dynamic stability, and toxicological endpoints. Of all the studied analogues, BPC2 has the lowest HOMO-LUMO gap and highest softness, implying higher chemical reactivity, whereas BPM has the highest gap and least softness, implying greater kinetic stability. DOS analysis found that BPG, BPM, and BPP have similar electronic distributions. The docked complexes showed the best docking score for BPPH, and stable interactions were confirmed through molecular dynamics in all top-ranked complexes. ADMET and PASS analysis found generally acceptable intestinal absorption, but also concerns of endocrine disruption, reproductive toxicity, nephrotoxicity, hepatotoxicity, and other organ-specific toxicities across numerous analogues. These findings highlight marked structure-dependent differences in the reactivity and toxicological potential of BP analogues and emphasize the value of integrating quantum chemical descriptors with in silico toxicity screening for toxicological assessment and safer design of next-generation BP substitutes.