Diffusion measurements vs. chemical shift titration for determination of association constants on the example of camphor-cyclodextrin complexes

Measurements on camphor-cyclodextrin complexes reveal that precise association constants are more easily determined by chemical shift titration. Diffusion measurements using HR-DOSY allow easy following of the complex composition at different concentration ratios and estimation of the binding energy. Linear dependence of the diffusion coefficients on the molecular mass of free and associated cyclodextrins has been observed in D2O. The solution structures of alpha- and beta-cyclodextrin complexes of camphor in D2O were deduced from intermolecular cross-relaxation data. Different preferential orientation in the 2:1 alpha-CD and 1:1 beta-CD species have been derived in contrast to the loose 1:1 complex with gamma-CD. Proton NMR chemical shift values proved to be much more sensitive to diastereomeric complex formation than diffusion coefficients.