Organic Chemistry

Experimental Characterization of the Association of Nine Novel Cyclodextrin Derivatives with Two Guest Compounds



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.


Thumbnail image of Gilson_SAMPL_submission.pdf

Supplementary material

Thumbnail image of SAMPL7_Kellett_Gilson_NMR-trans-methyl-cyclohexanol.pdf
SAMPL7 Kellett Gilson NMR-trans-methyl-cyclohexanol
Thumbnail image of SAMPL7_Kellett_Gilson_ITC_complexes.xlsx
SAMPL7 Kellett Gilson ITC complexes
Thumbnail image of SAMPL7_Kellett_Gilson_Hosts_SMILES.xlsx
SAMPL7 Kellett Gilson Hosts SMILES
Thumbnail image of SAMPL7_Kellett_Gilson_NMR-R-Rimantidine.pdf
SAMPL7 Kellett Gilson NMR-R-Rimantidine
Thumbnail image of SAMPL7_Kellett_Gilson_enthalpograms.pdf
SAMPL7 Kellett Gilson enthalpograms