Formation, Structure, and Stability of α- and β-Cyclodextrin Inclusion Complexes of Phenol and Benzoic Acid Derivatives in Vacuo and in Water

Inclusion complexations of α- and β-cyclodextrin (CD) with a series of phenol and benzoic acid derivatives both in vacuo and in water were investigated by semiempirical PM3 method. The inclusion systems with a higher negative value of complexation energy or interaction energy were found to have also a larger value of formation constant (Kf) in aqueous solution. The stability of β-CD inclusion complexes depended on the size/shape-fit between host and guest. A good size fitting between the volume of a guest molecule and the free space size of CD cavity effectively improved the stability of CD inclusion complex of the guest. Even though there was no appropriate molar volume ratio (MVR) of a guest to β-CD cavity, a good structural matching between the shape of a guest molecule and the arrangement of β-CD cavity should also obviously improve the stability of β-CD inclusion complex of the guest. Moreover, the CD cavity size exerted a big influence on the stability of these supramolecular complexes. There was an energetic advantage of larger than 45 kJ mol−1 in favor of the intermolecular complexations between α-CD and mono-ortho-substituted phenol derivatives relative to phenol or mono-para-substituted phenol derivatives.