Cavity Hydration and Competitive Binding in Methylated β-Cyclodextrin

Raman multivariate curve resolution (Raman-MCR) spectroscopy is used to measure the vibrational spectrum of water molecules in the cavity of an aqueous methylated β-cyclodextrin (Me-β-CD), as well as to quantify the competitive expulsion of those waters by benzene. The Me-β-CD cavity is found to contain 5-6 water molecules whose structure is remarkably similar to that of bulk water, although slightly more tetrahedral and with fewer weak hydrogen bonds. The binding constant of benzene to Me-β-CD, obtained using Raman-MCR, is found to be similar to that of benzene to β-CD (previously determined by other means). The competitive displacement of water by benzene in Me-β-CD is quantified by explicitly including the release of cavity-bound water molecules in the measured equilibrium constant.