Computational Biocompatibility and Safety Evaluation of Metal-Doped PET-Carbon Quantum Dots via Multi-Target Molecular Docking and ADMET Analysis on Human Proteins

Abstract

Polyethylene terephthalate-derived fluorescent carbon quantum dots (PET-CQDs) are promising nanomaterials for sensing and biomedical uses, yet their biological interactions after metal doping require careful evaluation. Here, we report an in silico assessment of pristine and dual-site (via graphitic [G] and carbonyl [O]) metal-doped PET-CQDs (Ca, Mg, Fe, Zn) using molecular docking against eight human proteins: HSA (distribution), CYP3A4 (metabolism), hemoglobin (systemic biocompatibility), transferrin (uptake), GST (detoxification), ERα (endocrine regulation), IL-6 (inflammation), and caspase-3 (cytotoxic signaling) together with ADMET profiling and DFT–docking correlation analysis. Docking affinities were compared with controls and ranged from −7.8 to −10.4 kcal·mol−1 across systems, with binding stabilized by π–π stacking, hydrogen bonding and metal–ligand coordination involving residues such as arginine, tyrosine and serine. Importantly, top-performing CQD variants differed by target: PET-CQDs, MgG_PET-CQDs and FeG_PET-CQDs were best for GST; ERα interacted favorably with all doped variants; IL-6 bound best to CaO_PET-CQDs and FeO_PET-CQDs (≈−7.1 kcal·mol−1); HSA favored CaG_PET-CQDs (−10.0 kcal·mol−1) and FeO_PET-CQDs (−9.9 kcal·mol−1); CYP3A4 bound most strongly to pristine PET-CQDs; hemoglobin favored MgG_PET-CQDs (−9.6 kcal·mol−1) and FeO_PET-CQDs (−9.3 kcal·mol−1); transferrin favored FeG_PET-CQDs; caspase-3 showed favored binding overall (pristine −6.8 kcal·mol−1; doped −7.4 to −7.6 kcal·mol−1). ADMET predictions indicated high GI absorption, improved aqueous solubility for some dopants (~18.6 mg·mL−1 for Ca-O/Mg-O), low skin permeability and no mutagenic/carcinogenic flags. Regression analysis showed frontier orbital descriptors (HOMO/LUMO) partially explain selective affinities for ERα and IL-6. These results support a target-guided selection of PET-CQDs for biomedical applications, and they call for experimental validation of selected dopant–target pairs.