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

Polyethylene terephthalate–derived fluorescent carbon quantum dots (PET-FCQDs) have emerged as promising nanomaterials for environmental sensing and potential biomedical applications. However, their biological safety profile remains underexplored, particularly when modified through metal doping for enhanced performance. In this study, we present a comprehensive in silico biocompatibility and safety evaluation of pristine and dual-site metal-doped PET-FCQDs (Ca, Mg, Zn, Fe) using multi-target molecular docking against key human proteins—Human Serum Albumin (HSA), Cytochrome P450 3A4 (CYP3A4), Hemoglobin, Transferrin, Caspase-3, Glutathione S-Transferase (GST), Estrogen Receptor alpha (ERα), and inflammatory markers (TNF-α, IL-6). The docking analysis revealed moderate to strong binding affinities, with variations in interaction profiles suggesting different implications for distribution, metabolism, and potential toxicity. Additionally, ADMET analysis indicated that all variants possessed high gastrointestinal absorption, low skin permeability, favorable blood-brain barrier penetration, and non-mutagenic, non-carcinogenic profiles. Metal doping enhanced aqueous solubility (up to ~18.6 mg/mL for Ca-O and Mg-O variants) but generally reduced lipophilicity (Log P: 0.38–0.64 vs. pristine: 1.13). All CQDs complied with major drug-likeness rules (Lipinski, Veber, Egan, Muegge) and displayed minimal CYP450 inhibition risk, indicating low potential for drug–drug interactions. Toxicity predictions classified all as low acute toxicity (Class III, LD₅₀ = 500–5000 mg/kg), with biodegradability dependent on doping site. These findings provide novel computational insights into the biocompatibility and pharmacokinetic behavior of PET-FCQDs and their doped analogues, supporting their safe integration in biomedical and environmental applications while highlighting site- and metal-dependent variations in safety profiles.