Al- and Ga-doped graphitic carbon nitride as a temozolomide nanocarrier platform: a DFT study of adsorption and interfacial interactions

Abstract

The rapid degradation and limited tumor accumulation of temozolomide (TMZ) remain important challenges in glioblastoma chemotherapy, motivating the development of nanocarrier systems that can improve TMZ retention and delivery. This study employed density functional theory (DFT) to evaluate the adsorption potential of two-dimensional graphitic carbon nitride (gCN) and its Al/Ga-doped variants (gCN-Al and gCN-Ga) as nanocarriers for TMZ delivery. A comprehensive analysis, including the electronic structure, natural bond orbital, quantum theory of atoms-in-molecules, and noncovalent interaction analyses, revealed that TMZ adsorbs onto the nanocarriers via spontaneous, physisorptive interactions, primarily by hydrogen bonding and van der Waals forces. The adsorption strength follows the order gCN-Ga > gCN-Al > pristine gCN, with gCN-Ga exhibiting the most favorable adsorption energy (−1.24 eV). Doping introduces new electronic states that narrow the HOMO–LUMO gap and enhance charge transfer, rationalizing the improved adsorption. The absence of imaginary frequency confirmed that each optimized geometry corresponds to a true minimum on the potential energy surface. Thermodynamic property analyses revealed the spontaneous and exothermic nature of the drug–nanocarrier complex formation. Recovery-time estimates suggest that TMZ desorption is thermally accessible, with Ga doping producing the longest predicted residence time. These results suggest that Al/Ga doping can modulate TMZ–gCN interactions at the molecular level and may provide a useful computational basis for future experimental evaluation of gCN-based TMZ delivery platforms.