Computational Modeling of Vinorelbine Encapsulation in Armchair Carbon Nanotubes: A Multi-Method Approach

In this work, the encapsulation behavior of the anticancer drug vinorelbine (VNR) within a finite hydrogen-terminated (۸,۸) armchair Single-Walled Carbon Nanotube (SWCNT) was investigated using a multiscale computational framework combining Density Functional Theory (DFT), molecular docking, Molecular Mechanics (MM), and Monte Carlo (MC) simulations. Geometry optimization and frequency calculations were performed at the B۳LYP/۶-۳۱۱+G** level to analyze structural stability and electronic properties of the drug-nanotube complex. Frontier molecular orbital analysis revealed a pronounced reduction in the HOMO-LUMO gap upon encapsulation, indicating increased electronic softness and enhanced charge-transfer capability within the hybrid system. Molecular Electrostatic Potential (MEP) mapping confirmed complementary electrostatic regions between vinorelbine and the nanotube interior, facilitating non-covalent stabilization dominated by π–π interactions. Molecular docking using AutoDock ۴.۲ yielded a binding energy of -۱۲.۵۳ kcal/mol, supporting favorable adsorption of vinorelbine within the nanotube cavity. Classical interaction energy calculations at the MM+ level were performed to further assess stability, while temperature-dependent Monte Carlo simulations (۲۹۸-۳۱۶ K) were conducted in various solvents (water, methanol, ethanol, DMF, and DMSO) using multiple force fields (Amber, OPLS, BIO, and MM+). Within the MM+ framework, ethanol exhibited the lowest calculated total energies among the investigated solvent environments, whereas water remains the most physiologically relevant medium for prospective biomedical applications. Overall, the integrated multiscale analysis indicates that hydrogen-passivated (۸,۸) armchair SWCNTs provide a favorable structural and electronic environment for vinorelbine encapsulation and represent promising candidates for carbon nanotube-based drug-delivery systems.

کلیدواژه ها:

Vinorelbine ، Single-walled carbon nanotube (SWCNT) ، density functional theory ، Molecular Docking ، Drug delivery