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

The complex formation of benzenesulfonate (BS) and alpha -cyclodextrin (alp ha -CD) is investigated by proton NMR and molecular surface area calculatio ns. The 1:1 binding constant K-1 is determined from dependence of the chemi cal shifts of the ortho proton of BS and the alpha -CD H3 on the concentrat ions of BS and alpha -CD. Using this K1 value, the chemical shift variation s 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 in corporated BS molecule. The penetration depth and rotation angle of the phe nyl group in the alpha -CD cavity are determined by best fitting to the obs erved 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 matc hing hydrophobic surface area decrease DeltaA(oo) is calculated as a functi on of the penetration depth and rotation angle of the phenyl group. The str ucture of the complex exhibiting the maximum DeltaA(oo) value is regarded a s the most stable structure. This is close to the NMR structure. The bindin g constant estimated from this DeltaA(oo) value is close to an observed val ue of K-1 = 9.75 dm(3) mol(-1). The hydrophobic interaction plays a predomi nant role in cyclodextrin inclusion. The concept of molecular recognition b y hydrophobic molecular surface areas is useful for the prediction of the b inding constant and the structure of the complex in a variety of other fiel ds as well.