1H-NMR Studies of the Inclusion Complexes between ?-Cyclodextrin and Adamantane Derivatives Using Both Exchangeable Hydroxy Protons and Non-Exchangeable Aliphatic Protons

Abstract

The inclusion complexes between α-cyclodextrin (α-CD) and adamantane, 1-adamantanol, 1-(hydroxymethyl)-adamantane, 2-adamantanol, and 1,3-adamantanediol in aqueous solution have been studied by 1H-NMR spectroscopy using both non-exchangeable and exchangeable protons. The complexation-induced 1H-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/α-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 1H signals for the free and bound α-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 α-CD. Both 1-adamantanol, and 1-(hydroxymethyl)-adamantane formed 1:1 inclusion complexes with α-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 α-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 α-CD and the guest molecules. The stoichiometry of the α-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 α-CD. This study showed how the hydroxy protons of α-CD could be used to obtain complementary information on the geometry and stability of inclusion complexes of α-CD.