Structural characterization and diffusional analysis of the inclusion complexes of fluoroadamantane with β-cyclodextrin and its derivatives studied via 1H, 13C and 19F NMR spectroscopy

This research conducts method development to study the diffusions of beta-cyclodextrin and its derivatives (collectively called beta-CDs) in biological systems. We proposed using fluoroadamantane (FA) beta-CD inclusion complexes as a model system to study the diffusion of beta-CDs by using F-19 self-diffusion NMR technique. The use of F-19 signal over H-1 signal arises from the advantage of being able to avoid the interference of H-1 signals from biological molecules and water. Another benefit of using FA is that the F-19 relaxation times are not significantly influenced by viscous biological solutions due to the tumbling nature of FA in beta-CD cavities. To synthesize the FA beta-CD inclusion complexes, a FA THF (tetrahydrofuran) solution and a beta-CD water solution were mixed together followed by lyophilization. The formation of the inclusion complexes in water were determined using HMQC and ROESY NMR experiments with the assistance of molecular modeling. To assess the method, both H-1 and F-19 diffusion NMR were carried out to study the diffusions of four typical FA beta-CD inclusion complexes. The results of this study illustrate that the diffusion coefficients obtained from the FA F-19 signal truly measure those of the beta-CDs' diffusion coefficients in water. Thus, the proposed technique using our model system is valid to be used to study the diffusions of beta-CDs in biological systems.