Aromatic Wall Extension of Glycoluril-Derived Molecular Clips Enhances Binding of Planar Aromatic Dyes

We report the synthesis and characterization of a new methylene-bridged glycoluril dimer featuring anthracene walls (H2). H2 displays good solubility in water (≥7 mM) but undergoes self-association at concentrations above 2 mM. ¹H NMR experiments establish that H2 binds cationic dyes inside its cavity with a π-stacked geometry that places the cationic residues at the ureidyl carbonyl portals of H2. The binding constants of both naphthalene-walled clip H1 and anthracene-walled clip H2 toward a panel of dyes were measured by direct or competitive UV/Vis or fluorescence titrations in phosphate buffered saline (PBS). Binding constants cover the range from 10³ - 10⁸ M^-1. Dyes that feature cationic NMe₂ groups bind more strongly than analogous dyes with cationic NH₂ groups. We find that π-extension of the aromatic walls from H1 to H2 generally results in an ≈ 10-fold increase in binding affinity. Host•guest complexes of H1 and H2 with planar cationic dyes benefit from substantial cation-π interactions.