Theoretical insights into functionalization-driven nitric oxide binding in calixarene scaffolds.

While calixarene-based supramolecular platforms have been widely investigated for the sensing of nitric oxide (NO), the underlying host-guest interactions remain poorly understood. In the present study, dispersion-corrected density functional theory calculations were employed to systematically investigate the influence of functionalization on the energetics, stability, and noncovalent interactions of host-guest complexes formed between NO and cone-shaped calix[4]arenes bearing electron-donating, electron-withdrawing, and sterically bulky substituents. The results demonstrate that lower-rim substitutions weaken NO binding by disrupting the near-symmetric cone arrangement of the aromatic rings, whereas sterically bulky upper-rim substitution enhances NO binding through an increased confinement effect and stronger dispersive interactions. In contrast, the electronic nature of the substituents exerts only a marginal influence on the NO⋯calixarene interaction energies. In addition, energetic analysis of two NO molecules confined within the calixarene cavity reveals the formation of a stable complex. However, the overall interaction energy is nonadditive because the simultaneous presence of two NO molecules reduces the extent of individual host-guest contacts, preventing each NO from interacting effectively with all four aromatic rings at the same time. Overall, this study provides molecular-level insights into NO encapsulation within calixarene cavities and establishes structure-interaction relationships relevant to the rational design of supramolecular NO sensing systems.