Coexistence of Two 1:1 Complexes of Oxyphenonium Bromide and (alpha)-Cyclodextrin

The complexation of 2-(2-cyclohexyl-2-hydroxy-2-phenylacetoxy)-N,N-diethyl-N-methylethanaminium bromide (oxyphenonium bromide, OB) and (alpha)-cyclodextrin ((alpha)-CD) in deuterium oxide was investigated by 500 MHz proton NMR spectroscopy, molecular mechanics, and molecular surface-area calculations. The ROESY spectrum revealed that two 1:1 complexes of OB and (alpha)-CD, the phenyl-in complex and the cyclohexyl-in complex, coexist simultaneously. The ROE intensities of intermolecular cross-peaks and molecular-mechanics calculations provided the structures of these complexes. The ROE intensities were well-correlated with the effective inter-proton distances for the estimated structures. The observed binding constant (70 dm3 mol^-1) was close to the sum of the binding constants of (alpha)-CD with phenol and cyclohexanol. This agreement supported the coexistence of the two complexes, and allowed us to estimate the mole fraction of the phenyl-in complex of 0.3. The chemical shift variations ((delta)(delta)OB-CD) at full binding for aromatic protons of OB are smaller than those of the benzenesulfonate-(alpha)-CD complex. Their ratio gave another estimate of the phenyl-in complex mole fraction (0.38). The averaged structure of OB in the two complexes was estimated from a comparison between the observed and theoretical shifts for four pairs of cyclohexyl protons; the phenyl and cyclohexyl groups in the complexes are slightly more distant than those in the free state. The structures of the phenyl-in complex and the cyclohexyl-in complex, estimated by hydrophobic molecular surface-area calculations, predicted binding constants closer to the observed ones than those by molecular-mechanics calculations.