A study of multiple complexation of α-, β- and γ-cyclodextrins:: Surprisingly differing stoichiometries of β- and γ-cyclodextrin complexes

Chromatographic, NMR and molecular modelling studies indicate that wbenzene-sym-tris-NNN-carbonyl-triglycylglycine N'-1-adamantylamide forms the strongest complex with beta-cyclodextrin (beta-CD), encapsulating the terminal adamantyl group. The analogous complex with gamma-CD is weaker with a deeper penetration of the guest into the host cavity, while the complex with alpha-CD is very weak. Remarkably, longitudinal relaxation times T-1 for the complexes with beta- and gamma-CD exhibit considerable differences in the signals for the adamantyl protons while no differences in the corresponding signals for the branch protons were found. Chromatographic measurements for the complexes with beta- and gamma-CD with the dendrimer revealed interesting differences in the stoichiometry of the dendrimer complexes in mixed solvents chosen because of the low solubility of the dendrimer under study and its CD complexes. Namely, in a 60:40 (v/v) methanol:water mixture the latter complex was undoubtedly of 1:1 stoichiometry while for the former the most plausible stoichiometry was 1:3. The binding constants of the multiple dendrimer complexes with P-CD (in 20:80(v/v) ethanol:water) of 1:1, 1:2 and 1:3 stoichiometry were estimated to be equal to ca 4 X 10(2) M-1, 1 X 10(2) M-1 and 25 X 10(3) M-1 while only a 1:1 complex with a binding constant of ca 6 X 10(2) M-1 (correlation factor R = 0.97) was found for the dendrimer complex with the larger gamma-CD (in 60:40 (v/v) methanol:water). (Attempts to fit the experimental curve assuming a mixture of complexes of 1:1 and 1:2 stoichiometry resulted in a value for the constant K-2 three orders of magnitude less than that for K-1.) The considerably larger value for K-3 compared with K-1 and K-2 seems to indicate that the dendrimer complex formation is cooperative. Such behaviour may be due to the more hydrophilic environment of the third adamantyl group in the 1:2 complex favouring its complexation. Chromatographic measurements for the compound mimicking one dendrimer branch yielded a 1:1 complex with gamma-CD with a binding constant of 1 X 10(2) M-1 while it was shown to complex at both adamantyl and benzene ends by beta-CD with the respective constants of 20 X 10(2) M-1 and 2 X 10(2) M-1.