Computational Modeling and Assessment of Si@GRP as an Innovative Esomeprazole Drug Delivery System: A DFT Investigation

ABSTRACT Esomeprazole (EPZ), a proton pump inhibitor (PPI), is widely used for acid‐related disorders but is associated with side effects, such as headaches, diarrhea, stomach pain, and neurological symptoms, raising concerns about its safety. This study employs density functional theory (DFT) at the PW6B95‐D3/LANL2DZ level to model a silicon‐doped graphene (Si@GRP) system co‐doped with sulfur (S), selenium (Se), and tellurium (Te) as a potential EPZ carrier. The HOMO–LUMO analysis indicates a moderate energy gap (Δ E = 2.23 eV), suggesting favorable reactivity, which aligns with nucleophilic sites observed in molecular electrostatic potential (MESP) plots. EPZ‐Si@GRP exhibits a moderate adsorption energy of ‐3.26 eV, indicating balanced adsorption and desorption characteristics. Stability is further supported by natural bond orbital (NBO) analysis, showing consistent E 2 values of 302.75, 296.6, 267.6, and 155.6 kcal/mol respectively. Quantum theory of atoms in molecules (QTAIM) analysis confirms robust bonding interactions, while non‐covalent interaction (NCI) plots highlight strong Van der Waals forces, reinforcing the non‐covalent nature of EPZ binding. These findings suggest that Si@GRP is a promising delivery material for EPZ, offering enhanced stability and controlled release potential.