Stability and geometry prediction for the inclusion complexes of mono- or 1,4-disubstituted benzenes and β-cyclodextrin using a genetic algorithm

The interaction energies of β-cyclodextrin (β-CD) and fourteen mono- and 1,4-disubstuted benzenes have been determined using consistent forcefield 91 (CFF91), and the geometries of the benzene derivatives were optimized by minimizing the energy using a genetic algorithm (GA). The Van der Waals and electrostatic interactions were considered as the binding forces. From the optimized energies, the linear relationships of the logarithm of the experimental association constants (ln K) with the total energy and with each energy factor were calculated. The calculation showed that there is an extremely good correlation between ln K and the total interaction energies. It indicated that the stability predicted by our method and the corresponding optimized model for the inclusion complexation are reliable. Furthermore, Van der Waals forces play a major role in the complex formation. The orientation of the guest molecules in the complexes obtained by GA is in good agreement with experimental studies.