Molecular recognition by β-cyclodextrin derivatives:: molecular dynamics, free-energy perturbation and molecular mechanics/Poisson-Boltzmann surface area goals and problems

The complexation of p-tert-butylphenyl p-tertbutylbenzoate and N-(p-tert-butylphenyl)-p-tert-butylbenzamide with a beta-cyclodextrin derivative formed by two cyclodextrin units linked by a disulfide bridge on one of the C6 atoms has been studied by computational methods. The better amide solubility and the better internal interactions of the ester complex explain the experimentally observed better association constant for the ester. The free-energy perturbation methodology and molecular mechanics/Poisson-Boltzmann surface area analysis have been used to explain the problem and to compare the results.