Supramolecular Cu ² ⁺ Sensing: A Mechanochemically Synthesized Imine Ligand and the Impact of β‐Cyclodextrin Host–Guest Chemistry

ABSTRACT A novel imine‐based ligand ( E )‐2‐(4‐(((2‐hydroxynaphthalen‐1‐yl)methylene)amino)phenyl)acetonitrile was synthesized via mechanochemistry from 4‐aminobenzylcyanide and 2‐hydroxy‐1‐naphthaldehyde, achieving >99% yield. The ligand demonstrated exceptional Cu 2+ ion sensing through colorimetric detection, with a rapid visual response and a low detection limit (4.7 × 10 − 8 M). Structural studies revealed 2:1 (L‐Cu 2 + ) complex formation, confirmed by Job's plot and 1 H NMR titration analyses. To enhance aqueous performance, host–guest complexation with β‐cyclodextrin was investigated. UV‐Vis and NMR spectroscopy confirmed 1:1 inclusion complex formation ( K a = 6.2 × 10 5 M − 1 ) through aminobenzyl cyanide insertion into the β‐CD cavity. The L‐β‐CD system significantly improved selectivity by reducing Al 3 + and Hg 2 + interference while maintaining comparable sensitivity (LOD = 4.8 × 10 − 8 M). Real‐world validation showed superior recovery rates (94.2%–110.0%) compared to free ligand (87.2%–114.7%). Biomolecular interaction studies revealed moderate DNA intercalation ( K a = 1.2×10 4 M − 1 ) attenuated by β‐CD inclusion ( K a = 3.5 × 10 3 M − 1 ), while bovine serum albumin (BSA) binding was slightly enhanced ( K a increased from 2.2 × 10 6 to 4.0 × 10 6 M − 1 ). This represents the UV‐Vis investigation of β‐cyclodextrin influence on Cu 2 + sensing, providing insights for an advanced supramolecular analytical platform.