Theoretical study of the inclusion processes of ethyl p-hydroxybenzoate with β-cyclodextrin: PM3MM and ONIOM2 calculations

The binding of the ethyl p-hydroxybenzoate with β-CD was investigated using PM3MM and ONIOM2 (MPW1PW91/6-31G: PM3MM) methods. Two modes of complexation were considered for studying such complex. In A complex the OH group of the guest was pointed toward secondary hydroxyls of β-CD, while in B complex the OH group was directed to primary hydroxyls. The lowest energy structure obtained with ONIOM2 for B complex (the preferred complex) showed that the aromatic ring is totally embedded in β-CD while alkyl chain remains outside the cavity. This preferred arrangement increases intermolecular and H-bond interactions between ethyl p-hydroxybenzoate and β-CD. This is confirmed by NBO analysis.

► Two models of ethyl-p-hydroxybenzoate/β-CD inclusion complex were investigated using PM3MM and ONIOM2 methods.
► The B complex was predicted to be the most stable one.
► NBO analysis gives more information about intermolecular interactions between ethyl-p-hydroxybenzoate and β-CD.