Complex formation of benzenesulfonate-α-cyclodextrin estimated from NMR and hydrophobic molecular surface areas

The complex formation of benzenesulfonate (BS) and alpha -cyclodextrin (alpha -CD) is investigated by proton NMR and molecular surface area calculations. The 1:1 binding constant K-1 is determined from dependence of the chemical shifts of the ortho proton of BS and the alpha -CD H3 on the concentrations of BS and alpha -CD. Using this K1 value, the chemical shift variations of all protons of BS and alpha -CD with complex formation are determined. The chemical shift variations of all alpha -CD protons are calculated from the Johnson-Bovey theory on the basis of the ring current effect of the incorporated BS molecule. The penetration depth and rotation angle of the phenyl group in the alpha -CD cavity are determined by best fitting to the observed chemical shift variations: the penetration depth is close to that in the crystal structure of the BS-alpha -CD complex and the rotation angle is different by 30 degrees. This structure is consistent with the intensities of intermolecular cross-peaks in the ROESY spectrum. Furthermore, the matching hydrophobic surface area decrease DeltaA(oo) is calculated as a function of the penetration depth and rotation angle of the phenyl group. The structure of the complex exhibiting the maximum DeltaA(oo) value is regarded as the most stable structure. This is close to the NMR structure. The binding constant estimated from this DeltaA(oo) value is close to an observed value of K-1 = 9.75 dm(3) mol(-1). The hydrophobic interaction plays a predominant role in cyclodextrin inclusion. The concept of molecular recognition by hydrophobic molecular surface areas is useful for the prediction of the binding constant and the structure of the complex in a variety of other fields as well.