We investigate the binding of native β-cyclodextrin (β-CD) and eight novel β-CD derivatives with two different
guest compounds, using isothermal calorimetry (ITC) and 2D NOESY NMR. In all cases, the stoichiometry is 1:1
and binding is exothermic. Overall, modifications at the 3’ position of β-CD, which is at the secondary face, weaken
binding by several kJ/mol relative to native β-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.
Experimental characterization of the association of β-cyclodextrin and eight novel cyclodextrin derivatives with two guest compounds
