Displacement of “high-energy” water from a non-polar host cavity has been proposed as a driving force for supramolecular host-guest binding processes. For instance, it has been suggested that liberation of water from cyclodextrin (CD) cavities leads to an enthalpy gain because the expelled water molecules can form better hydrogen bonds in the bulk medium than inside the non-polar cavity. In addition, calorimetric measurements and molecular-dynamics (MD) simulations of binding in cucurbiturils have found a correlation between the number of water molecules in the free host cavity and their binding constants. This has been interpreted as implying that host-guest binding affinity is promoted by screening of cavity water molecules from contact with bulk water. However, no previous studies have reported direct experimental observations of the structure of water in such non-polar host cavities in aqueous solution. Here, we do so by combining Raman spectroscopy and multivariate curve resolution (Raman-MCR) to measure the hydration-shell vibrational spectra of water-filled and benzene-filled methylated β-cyclodextrin (Me-β-CD) host molecules. Our results reveal that there are 5-6 water molecules in the free Me-β-CD host, in reasonable agreement with values inferred from previously reported MD simulations as well as the crystal structure of non-methylated β-CD. Moreover, our results show that the cavity-bound water has a structure that is quite similar (but not identical) to bulk water. In addition, we demonstrate that Raman-MCR may be used to determine the binding constant of benzene to Me-β-CD and find that it is comparable to that for benzene binding to non-methylated β-CD. 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.

Cavity hydration and competitive binding in methylated β-cyclodextrin

2019 Fall National Meeting

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.