Exploring Graphitic Carbon Nitride as Novel Drug Delivery System for Hesperetin (Anticancer Drug): Insights From DFT Calculations and Molecular Dynamics Simulations

ABSTRACT In the present work, density functional theory (DFT) and molecular dynamics (MD) simulations were employed to explore the interaction between Hesperetin (HST), an anticancer drug, and 2D graphitic carbon nitride (GRP) nanocarrier designed for targeted drug delivery. The B3LYP/B3LYP‐D3 functionals and the 6‐31G (d,p) basis set were used for DFT calculations in both gaseous and solvent environments. The outcomes reveal exothermic adsorption (adsorption energy = −0.18 eV) of HST on the GRP nanocarrier, suggesting increased stability for enhanced drug delivery in biological systems. Calculations of orbital energy and density of state (DOS) demonstrate a reduced HOMO–LUMO energy gap (3.15 eV) of GRP upon interaction with HST. In an aqueous medium, the HST@GRP complex exhibits a higher dipole moment (3.48 D) compared to the gas phase (1.60 D), facilitating effective drug transportation. Charge decomposition analysis (CDA) identifies an orbital overlap between HST and GRP, supported by natural bond orbitals showing evidence of charge transfer. Computational UV–visible spectra closely match with experimental data. The elucidation of the photoinduced electron transfer (PET) mechanism explains fluorescence quenching. In summary, these findings suggest the potential of GRP as an efficient nanocarrier for HST drug delivery, encouraging further exploration of 2D nanomaterials in drug transport systems.