Computational investigation of Belzutifan drug delivery mechanisms using SiC nanocrystals via combined DFT and molecular dynamics approaches.

This study employs density functional theory (DFT) and molecular dynamics (MD) simulations to investigate silicon carbide (SiC) nanocrystals as carriers for the anticancer drug Belzutifan. Among tested functional groups (-H, -OH, -NH₂, -COOH), carboxyl-functionalized SiC (SiC-COOH) exhibits superior drug loading capacity with an adsorption energy of -1.03 eV, representing a 25% improvement over conventional carbon-based carriers. The SiC-COOH system demonstrates exceptional stability with a formation energy of -5.42 eV/atom and a remarkably high dipole moment of 142.1 D, facilitating enhanced solubility. Electronic structure analysis reveals significant charge transfers (-0.25e) from Belzutifan to the nanocrystal, accompanied by a substantial reduction in the HOMO-LUMO gap from 5.427 eV (pristine SiC) to 3.41 eV (Belzutifan@SiC-COOH complex), indicating improved electronic coupling. MD simulations confirm the complex's stability under physiological conditions, maintaining structural integrity with root-mean-square deviation (RMSD) values below 2.5 Å throughout the 5 ps simulation. Characteristic shifts in optical spectra (200-600 nm range) and IR vibrational modes (15-40 cm⁻¹) provide clear spectroscopic signatures of successful drug adsorption. The combination of strong binding (-1.03 eV adsorption energy), maintained biocompatibility, and tunable electronic properties positions functionalized SiC nanocrystals as a promising platform for targeted Belzutifan delivery, with potential applications in photo-triggered release systems.