We investigate the binding of native β-cyclodextrin (β-CD) and eight novel β-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 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.

我们使用等温量热法和 2D NOESY NMR 研究了天然 β-环糊精 (β-CD) 和八种新型 β-CD 衍生物与两种不同客体化合物的结合。在所有情况下，化学计量比为 1:1，结合是放热的。总体而言，在 β-CD 的 3' 位置（位于二级面）处的修饰相对于天然 β-CD 减弱了几个 kJ/mol 的结合，而在 6' 位置（一级面）处的修饰保持或在一定程度上降低了结合亲和力。结合焓的变化大于结合自由能的变化，因此观察到熵-焓补偿。使用 NOESY NMR 表征结合构象表明，客体的极性基团可能位于任一面，具体取决于主体分子，并且在某些情况下，两个方向都存在。