DFT Investigation of Primidone Loading on Chitosan-Decorated Graphene Sheets: The Role of Oligomer Length

Primidone (PRM) is a widely used anticonvulsant; however, its therapeutic efficacy is restricted by poor bioavailability and systemic toxicity. Pristine graphene (GN) offers a high specific surface area but lacks hydrophilicity. Here, we examine the influence of chitosan oligomer length (monomer, dimer, trimer) on the adsorption behavior of PRM onto GN using density functional theory (DFT) at B3LYP/6‑31G(d). Key metrics include interaction energies (E_int), frontier orbital gaps (E_gap), thermodynamic profiles (ΔG, ΔH, ΔS) under implicit water, natural bond orbital (NBO) stabilizations E(2), and optical transitions. Among the four systems—pristine GN, GN/monomer, GN/dimer, and GN/trimer—the GN/dimer complex yields the strongest interaction (–148.32 kJ mol⁻¹), surpassing pristine GN (–110.45) and GN/monomer (–32.14). This dimer configuration reduces E_gap from 0.0381 a.u. (free GN) to 0.0127 a.u., indicating enhanced electronic responsiveness. All systems exhibit negative ΔG in water, confirming spontaneous binding. The GN/dimer‑PRM complex also shows the highest oscillator strength (f=0.0072) and maximum NBO stabilization energy (31.85 kcal mol⁻¹). We conclude that the chitosan dimer represents the optimal chain length for functionalizing graphene with respect to PRM delivery, balancing surface coverage and steric accessibility.