Metal–Metalloid\nModified C<sub>36</sub> Fullerene:\nA Dual Role in Drug Delivery and Sensing for Anticancer Chlormethine\nExplored through DFT and MD Simulations

Spurred by the latest developments and growing utilization\nof zero-dimensional\n(0D) drug delivery and drug sensors, this investigation examines the\npossibilities of the 0D C<sub>36</sub> fullerene for drug delivery\nand the detection of the anticancer drug chlormethine (CHL), the overabundance\nof which poses a significant threat to living organisms. This study\nemploys density functional theory and ab initio molecular dynamics\n(AIMD) simulations (AIMD) to evaluate and gain insights into the interaction\nmechanisms between pristine C<sub>36</sub> fullerene, metal–metalloid\n(MM)-modified C<sub>36</sub> fullerene (with Al, Fe, and B), and the\nanticancer drug CHL. It is observed that in the gas phase, the CHL\ndrug molecule adsorbs onto the fullerenes in the following order:\nB–C<sub>36</sub> > Fe–C<sub>36</sub> > Al–C<sub>36</sub> > C<sub>36</sub>. However, when considering the solvent\neffect, the adsorption energy of the CHL drug molecule on B–C<sub>36</sub> increases, indicating chemisorption behavior. This implies\nthat B–C<sub>36</sub> could be a promising candidate for drug\ndelivery applications, particularly for the CHL anticancer drug. In\ncontrast, the adsorption energy of the CHL drug molecule on Fe–C<sub>36</sub> decreases with the presence of the solvent, resulting in\nintermediate physisorption. Due to its minimal recovery time, excellent\nsensing response, intermediate physisorption, and shorter interatomic\ndistance compared to C<sub>36</sub> and Al–C<sub>36</sub> fullerenes,\nFe–C<sub>36</sub> is well-suited as a drug sensor for CHL.\nAIMD simulations demonstrate that the B–C<sub>36</sub>/CHL\nand Fe–C<sub>36</sub>/CHL complexes are well-equilibrated and\nhighly stable in the aqueous phase at 300 and 310 K respectively,\nwith no evidence of bond breakage or formation. The structural stability\nobserved, even with temperature fluctuations, indicates that the electrostatic\ninteractions are robust enough to maintain cohesion of the fragments.