1H-NMR studies of the inclusion complexes between α-cyclodextrin and adamantane derivatives using both exchangeable hydroxy protons and non-exchangeable aliphatic protons

The inclusion complexes between alpha-cyclodextrin (alpha-CD) and adamantane, 1-adamantanol, 1-(hydroxymethyl)adamantane, 2-adamantanol, and 1,3-adamantanediol in aqueous solution have been studied by H-1-NMR spectroscopy using both non-exchangeable and exchangeable protons. The complexation-induced H-1-NMR shifts (CIS) and NOES of non-exchangeable protons, as well as the CIS, NOES, temperature coefficients, and linewidth of signals from exchangeable hydroxy protons have been determined. The stoichiometry of the adamantane/alpha-CD complex could not be determined due to the low solubility of adamantane. However, for 0.11 equivalent of adamantane added, two sets of separate H-1 signals for the free and bound alpha-CD were observed. The signal from O(3)H in the complexed form appeared narrow and upfield shifted with a low-temperature coefficient indicating reduced hydration inside the hydrophobic cavity of alpha-CD. Both 1-adamantanol, and 1-(hydroxymethyl)adamantane formed 1:1 inclusion complexes with alpha-CD and only one set of NMR signals was observed. The CIS and NOEs suggested that both complexes had similar structures. The O(2)H signal of alpha-CD was broadened at low temperature and became narrower as the temperature raised. The broadening increased with higher concentration of guest suggesting interaction between O(2)H of alpha-CD and the guest molecules. The stoichiometry of the alpha-CD/2-adamantanol complex could not be determined with certainty, but the NMR data suggested equilibrium between 2:1 and 1:1 complex. As with adamantane, a sharp and upfield shifted O(3)H signal with a very low-temperature coefficient was observed. No inclusion complex was formed between 1,3-adamantanediol and Lx-CD. This study showed how the hydroxy protons of alpha-CD could be used to obtain complementary information on the geometry and stability of inclusion complexes of alpha-CD.