Ullah, NajeebNajeebUllahKarim, AmirAmirKarimIqbal, Muhammad AdnanMuhammad AdnanIqbalMalekshah, Rahime EshaghiRahime EshaghiMalekshahAli, SaqibSaqibAliHaribabu, JebitiJebitiHaribabuHsu, Sodio Chih NengSodio Chih NengHsu2025-10-102025-10-10202509485023; 16102940https://hdl.handle.net/20.500.12740/23415Context: Recent studies on drug delivery systems incorporating boron nitride nanostructures (BNNTs) highlight their excellent chemical stability and non-cytotoxic properties, positioning them as a promising platform for drug release in biomedical applications. This study aimed to optimize the mono-nuclear structures of Cu(II) and Zn(II) complexes and to functionalize zigzag (13, 13) boron nitride nanotubes with glutamic acid (GABNNTs). Based on Monte Carlo, the results revealed that complexes 6 and 19 exhibited stronger interactions with GABNNTs, attributed to π-π stacking between bipyridine/phenanthroline ligands and GABNNTs. This interaction suggests a greater challenge in their release compared to other compounds. The interaction energy analysis further revealed that complexes 1, 4, and 12/GABNNTs exhibited the lowest stability, indicating weaker binding interactions between these complexes and the GABNNT surface. The adsorption of all complexes on GABNNTs was primarily found to be physisorption. Molecular docking with mushroom tyrosinase (2Y9X) identified complexes 5, 10, 11, 15, and 20 as having the strongest interactions, a trend that is partially supported by chemical hardness analysis. However, DFT-D results indicated that complexes 5, 11, and 20 exhibited the lowest chemical stability, suggesting a trade-off between strong interactions and lower stability in these complexes. Methods: The energies of these systems were estimated using dispersion-corrected density functional theory (DFT-D) calculations performed in Materials Studio 2017. To evaluate the drug delivery potential of GABNNTs for Cu(II) and Zn(II) complexes, the Monte Carlo (MC) method was employed. The structural and electronic properties, as well as the relationship between biological activities and ΔE<inf>g</inf>, were analyzed by calculating the HOMO–LUMO energy gap using the dispersion-corrected density functional theory (DFT-D) method. Molecular docking was used to interact with mushroom tyrosinase (2Y9X). © 2025 Elsevier B.V., All rights reserved.restrictedAccessDRUG DELIVERY SYSTEMFUNCTIONALIZED BORON NITRIDE NANOTUBEGLUTAMIC ACIDMONTE CARLO SIMULATIONTYROSINASE INHIBITIONBIPYRIDINEMONOPHENOL MONOOXYGENASEPHENANTHROLINEZINC IONCOPPERZINCBORON COMPOUNDSBORON NITRIDECOORDINATION COMPLEXESENZYME INHIBITORSBORON NITRIDE NANOTUBECUPRIC IONOXYGENASE INHIBITORBORON DERIVATIVECOORDINATION COMPOUNDENZYME INHIBITORNANOTUBEANTIOXIDANT ACTIVITYARTICLEBLOOD BRAIN BARRIERCONTROLLED STUDYDENSITY FUNCTIONAL THEORYDNA BINDINGDRUG DESIGNDRUG RELEASEDRUG STABILITYELECTROPHILICITYENZYME INHIBITIONHYDROGEN BONDMOLECULAR DOCKINGMONTE CARLO METHODMUSHROOMNANOPHARMACEUTICSNONHUMANPHYSISORPTIONSTATIC ELECTRICITYCHEMISTRYMOLECULAR DOCKING SIMULATIONNANOTUBESArtículo https://doi.org/10.1007/s00894-025-06355-2