Structure-Property Relationships in Heteroatom-Doped g-C 3 N 4 Nanocarriers for Cimetidine: A Computational Study

Abstract

In this work, a comprehensive density functional theory (DFT) and Monte Carlo molecular dynamics (MD) investigation is conducted to evaluate the interaction of cimetidine (Cmt), an anti-ulcer drug, with pristine and X-doped C 3 N 4 surfaces (X = B, S, P, and Si). Adsorption energy calculations reveal favorable and thermodynamically stable binding of cimetidine on pristine C 3 N 4 as well as B-, S-, and Si-doped C 3 N 4 surfaces, characterized by moderate physisorption energies suitable for reversible drug loading and release. Natural bond orbital (NBO) and density of states (DOS) analyses demonstrate pronounced charge transfer and orbital hybridization upon adsorption, particularly for doped systems, confirming the role of dopants in tuning surface reactivity. QTAIM and noncovalent interaction (NCI) analyses identify a combination of hydrogen bonding, electrostatic, and van der Waals interactions governing adsorption stability. Molecular dynamics analysis reveals that B@C 3 N 4 exhibits pronounced time-dependent diffusion behavior, characterized by reduced cimetidine mobility at short simulation times (100 ps) and enhanced diffusion at longer times (500 ps), indicating effective initial drug retention followed by facilitated release. In contrast, Si@C 3 N 4 exhibits more uniform diffusion behavior across both time scales, suggesting steady and controlled drug delivery. The results highlight doped C 3 N 4 as a promising platform for controlled cimetidine delivery, providing fundamental insights into the structure-property relationships governing drug-nanocarrier interactions.