Why 2,6-di-methyl-beta-cyclodextrin can encapsulate OH-substituted naphthalenes better than beta-cyclodextrin: Binding pose, non-covalent interaction and solvent effect

Naphthalenes, a class of persistent organic pollutants, are difficult to remove from environment due to their low water solubility. beta-cyclodextrin (beta-CD) and its derivatives can encapsulate these compounds and enhance their solubility. For OH-substituted naphthalenes, several inclusion complexes with beta-CD and 2,6-di-methyl-beta-CD (DMCD) of varying stabilities were reported. However, the role of non-covalent interaction was not defined and the binding mechanisms remain vague. We use a molecular dynamics/quantum mechanics/continuum solvent model to explore the inclusion mechanisms of these systems. Both the measured binding modes and binding trend are well reproduced by our computations. The host-guest non-covalent interaction favors the beta-CD complexes, while the hydrophobic interaction favors the DMCD complexes, and the latter plays a more important role in determining the binding trend. A correlation between the polarizability of the inclusion complex as measured by its dipole moment and hydrophobic interaction is also revealed.