Experimental characterization of the association of β-cyclodextrin and eight novel cyclodextrin derivatives with two guest compounds

We investigate the binding of native beta-cyclodextrin (beta-CD) and eight novel beta-CD derivatives with two different guest compounds, using isothermal calorimetry and 2D NOESY NMR. In all cases, the stoichiometry is 1:1 and binding is exothermic. Overall, modifications at the 3 ' position of beta-CD, which is at the secondary face, weaken binding by several kJ/mol relative to native beta-CD, while modifications at the 6 ' position (primary face) maintain or somewhat reduce the binding affinity. The variations in binding enthalpy are larger than the variations in binding free energy, so entropy-enthalpy compensation is observed. Characterization of the bound conformations with NOESY NMR shows that the polar groups of the guests may be situated at either face, depending on the host molecule, and, in some cases, both orientations are populated. The present results were used in the SAMPL7 blinded prediction challenge whose results are detailed in the same special issue of JCAMD.

Automated summary

The study found that modifications at different positions of beta-cyclodextrin can affect its binding affinity with guest compounds, with modifications at the 3' position weakening the binding and modifications at the 6' position maintaining or slightly reducing it. Additionally, the polar groups of the guests may be situated on different faces, and entropy-enthalpy compensation phenomenon is observed.