Exploring the Role of Hydrogen Bonding in Cyclodextrin─Naphthalenediimide Binding Orientation

We report a systematic investigation of alkyl-substituted naphthalenediimide (NDI) derivatives and their host-guest interactions with α- and β-cyclodextrins, elucidating the role of hydrogen bonding in dictating the binding orientation of NDIs with α-CD and β-CD. Thermodynamic, spectroscopic, and computational analyses reveal distinct binding modes for α-CD and β-CD. Isothermal titration calorimetry (ITC) establishes the interaction of NDIs with α-CD and β-CD, while induced circular dichroism (ICD) indicates a partial inclusion for α-CD, and a rim-anchored externally associated geometry for β-CD. ¹H NMR and ROESY further differentiated the binding orientations, showing wider-rim contacts for NDIs with α-CD and narrow-rim contacts with β-CD. Density functional theory and QTAIM pointed to stronger, geometry-specific noncovalent interactions for β-CD, consistent with directional hydrogen bonding involving carbonyl groups in NDIs. ¹³C NMR titrations showed a selective downfield shift in two of the four carbonyls of NDIs that bind with β-CD, confirming the presence of hydrogen bonding. These results collectively demonstrate that targeted hydrogen bonding can control the position and orientation of the chromophore in β-CD complexes, thereby opening up avenues for rational design of noncovalent architectures.