The complex formation of alpha-cyclodextrin (alpha-CD) with propanesulfonate (PS) and propanol (PrOH) was investigated by proton NMR spectroscopy and molecular surface area calculations. The 1: 1 binding constant, K-1, was determined from dependence of the chemical shift of the propyl beta-methylene protons on the alpha-CD concentration to be 23.0 and 21.3 M-1 for PS and PrOH. Quantitative analysis of the ROESY spectra showed that the propyl groups of PS and PrOH penetrate from the secondary alcohol side of alpha-CD. This penetration side of PrOH is opposite to that in the crystal. The observed vicinal spin-spin coupling constant of the HC(5)-C(6)HR system of PS-alpha-CD indicated that the H5 and H6R atoms are in the gauche arrangement, though they are in the trans arrangement in the crystal. The observed vicinal coupling constant of the HCalpha-CbetaH system of PS-alpha-CD indicated that the sulfur and Cgamma atoms are restricted around the trans arrangement because of the hindered rotation of the Calpha-Cbeta bond, although the Calpha-Cbeta bond of PrOH in the complex rotates freely. These ROESY and coupling constant data allowed us to propose the solution structures of the complexes. Furthermore, three molecular surface area decreases with docking were calculated as a function of the penetration depth of the propyl group. For the solution structures of these complexes, the matching hydrophobic and hydrophilic surface areas, DeltaA(oo) and DeltaA(ww) of the alpha-CD and guest molecules exhibited maxima, and the mismatching hydrophobic and hydrophilic surface area, DeltaA(ow) had a minimum. These are very stable structures from the viewpoint of hydrophobic and hydrophilic interactions. The concept of molecular recognition by hydrophobic and hydrophilic interactions in water will be applicable to other complexes.
