Evaluating the drug delivery potential of functionalized calix [4] arene for carboplatin-drug: A computational study analyzing static electric field and solvent effects through DFT, TD-DFT, and NLO techniques.

Targeted and precise drug delivery using nanomaterials remains a major goal in cancer therapy. In this study, the interaction of carboplatin, a key anticancer drug, with pristine and functionalized calix[4]arene (CHO, COOH, NH2, NO2) was investigated under varying solvent environments (water, ethanol, DMSO) and static electric fields (SEF) using density functional theory (DFT) at the GD3-Cam-B3LYP/Lanl2DZ level. The negative adsorption energy (Eads) and enthalpy (ΔH) values confirm exothermic and thermodynamically favorable interactions across all complexes. Among them, CC-NO2-II exhibits the highest Eads (-32.54 kcal/mol in the gas phase), while CC-COOH derivatives demonstrate exceptional stability across solvents due to strong hydrogen bonding and dipolar interactions. Under SEF (z+0.05 a.u.), CC-NH2 exhibits the most significant enhancement in Eads (-276.01 kcal/mol), highlighting its potential for field-assisted drug delivery. The CC-COOH complex shows the greatest Egap reduction (83.6 %), attributed to its high dipole moment and polarizability. Non-covalent interactions, including hydrogen bonding, van der Waals forces, and electrostatic interactions, were confirmed through atoms-in-molecules (AIM) and reduced density gradient (RDG) analyses. These findings underscore the potential of functionalized calix [4] arene as an efficient and tunable drug carrier, with external fields and solvents serving as effective modulation factors. This work provides valuable insights for the molecular design of advanced, field-responsive drug delivery systems for targeted chemotherapy applications.