Interaction of 5-Fluorouracil on the Surfaces of Pristine and Functionalized Ca(12)O(12) Nanocages: An Intuition from DFT

[Image: see text] The utilization of nanostructured materials for several biomedical applications has tremendously increased over the last few decades owing to their nanosizes, porosity, large surface area, sensitivity, and efficiency as drug delivery systems. Thus, the incorporation of functionalized and pristine nanostructures for cancer therapy offers substantial prospects to curb the persistent problems of ineffective drug administration and delivery to target sites. The potential of pristine (Ca(12)O(12)) and formyl (−CHO)- and amino (−NH(2))-functionalized (Ca(12)O(12)–CHO and Ca(12)O(12)–NH(2)) derivatives as efficient nanocarriers for 5-fluorouracil (5FU) was studied at the B3LYP-GD3(BJ)/6-311++G(d,p) theoretical level in two electronic media (gas and solvent). To effectively account for all adsorption interactions of the drug on the investigated surfaces, electronic studies as well as topological analysis based on the quantum theory of atoms in molecules (QTAIM) and noncovalent interactions were exhaustively utilized. Interestingly, the obtained results divulged that the 5FU drug interacted favorably with both Ca(12)O(12) and its functionalized derivatives. The adsorption energies of pristine and functionalized nanostructures were calculated to be −133.4, −96.9, and −175.6 kcal/mol, respectively, for Ca(12)O(12), Ca(12)O(12)–CHO, and Ca(12)O(12)–NH2. Also, both topological analysis and NBO stabilization analysis revealed the presence of interactions among O(3)–H(32), O(27)–C(24), O(10)–C(27), and N(24)–H(32) atoms of the drug and the surface. However, 5FU@Ca(12)O(12)–CHO molecules portrayed the least adsorption energy due to considerable destabilization of the molecular complex as revealed by the computed deformation energy. Therefore, 5FU@Ca(12)O(12) and 5FU@Ca(12)O(12)–NH(2) acted as better nanovehicles for 5FU.