Molecular Modeling of Host-Guest Complexes: A Comparative Study of 𝛽-Cyclodextrin, Calix[4]arenesulfonate, and Cucurbit[7]uril with Bicyclic Azoalkane Guests
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Abstract
This study examines the inclusion complexation of three bicyclic azoalkane derivatives (DBH, DBO, DBN) with macrocyclic hosts 𝛽 -cyclodextrin (BCD), calix[4]arenesulfonate (C4S), and cucurbit[7]uril (CB7). Using molecular docking, Hartree–Fock (HF/6-31G(d,p)), and PM7/PCM methods, binding energies, orientations, and electronic properties were evaluated in gas-phase and aqueous environments. Docking revealed negative binding energies with azo groups consistently oriented toward host cavities. HF calculations confirmed thermodynamic stability, showing negative complexation energies and large HOMO–LUMO gaps. PM7/PCM analysis highlighted solvation effects, where water enhanced hydrophobic interactions and stabilized guest encapsulation, especially in CB7. Comparative results indicated CB7 consistently forms the most stable complexes, followed by C4S and BCD, due to favorable cavity size, steric compatibility, and electrostatic complementarity. Overall, the findings provide insights into host–guest recognition mechanisms, offering guidance for designing efficient supramolecular systems with potential applications in molecular encapsulation and drug delivery.
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