Host–guest geometry in paramagnetic cavitands elucidated by ¹⁹F electron-nuclear double resonance

Elucidating structural information of supramolecular host–guest systems is pivotal for understanding molecular recognition and designing functional materials. This study explores the binding modes of fluorinated benzylamine guests in cyclodextrin-based paramagnetic cavitands, employing Gd(III)-capped cyclodextrins (Gd-a-CD and Gd-b-CD, comprising six and seven glucopyranoside units, respectively) and high-field ¹⁹F electron-nuclear double resonance (ENDOR). The ¹⁹F ENDOR spectra revealed distinct behaviors based on the fluorine position and cyclodextrin cavity size. For para-fluorinated benzylamine guests, Gd-b-CD displayed a bimodal distribution of Gd–F distances, corresponding to two distinct binding modes, whereas Gd-a-CD exhibited a single binding mode. In contrast, meta-fluorinated benzylamines demonstrated a single binding mode for both Gd-a-CD and Gd-b-CD, underscoring the influence of cavity size and fluorine substitution in the guest on binding specificity. ENDOR measurements performed at the EPR central transition of Gd(III) are generally expected to yield Gd–F distances without orientation-specific details. Surprisingly, in Gd-CDs systems, an unexpected orientation selectivity was observed, enabling the extraction of both Gd–F distances and orientation of the guest molecule relative to the cavitand’s Gd(III) zero-field splitting (ZFS) tensor. This two-faceted capability of ¹⁹F-ENDOR allows for determining host–guest complexation geometry and provides insights into ZFS orientation within the cavitand structure.