Computational insights into solvent encapsulation and host–guest recognition by calix[4]arene

The current study investigates a series of calix[4]arene/organic solvent inclusion complexes formed with twelve carefully selected guest molecules. The analyzed guest molecules can be categorized as polar protic (methanol, ethanol, water, nitromethane), polar aprotic (dimethyl sulfoxide, acetone, acetonitrile, tetrafluoromethane), and non-polar (benzene, toluene, cyclohexane, diethyl ether) solvents. These systems were chosen to explore how solvent encapsulation influences host-guest interactions and the electronic properties of the calix[4]arene framework. Inclusion complexes were optimized in both gas and solvent phases using the dispersion-corrected B3LYP-D3 hybrid functional in combination with the 6-311+G(d,p) basis set. All described complexes are energetically favorable, with CX[4]/DMSO exhibiting the highest interaction energy of - 76.57 kJ/mol in the gas phase. Thermodynamic analyses including enthalpy and Gibbs free energy changes support the stability of the systems. The frontier molecular orbital analysis revealed shifts in HOMO-LUMO densities upon complexation, and energy gaps range between 4.46 and 5.25 eV confirming the kinetic stability of CX[4]/solvent systems. The interaction region indicator and QTAIM analysis revealed the nature and topology of non-covalent interactions. Moreover, molecular electrostatic potential maps highlight electrophilic and nucleophilic regions in the most stable inclusion complexes. These findings provide insight into the fundamental interactions governing solvent inclusion within calix[4]arene, with implications for host-guest chemistry and molecular recognition applications.