Glycoluril-Derived Molecular Clips are Potent and Selective Receptors for Cationic Dyes in Water

Molecular clip 1 remains monomeric in water and engages in host-guest recognition processes with suitable guests. We report the K-a values for 32 1.guest complexes measured by H-1 NMR, UV/Vis, and fluorescence titrations. The cavity of 1 is shaped by aromatic surfaces of negative electrostatic potential and therefore displays high affinity and selectivity for planar and cationic aromatic guests that distinguishes it from CB[n] receptors that prefer aliphatic over aromatic guests. Electrostatic effects play a dominant role in the recognition process whereby ion-dipole interactions may occur between ammonium ions and the C=O groups of 1, between the SO3- groups of 1 and pendant cationic groups on the guest, and within the cavity of 1 by cation-pi interactions. Host 1 displays a high affinity toward dicationic guests with large planar aromatic surfaces (e.g. naphthalene diimide NDI + and perylene diimide PDI +) and cationic dyes derived from acridine (e.g. methylene blue and azure A). The critical importance of cation-pi interactions was ascertained by a comparison of analogous neutral and cationic guests (e.g. methylene violet vs. methylene blue; quinoline vs. N-methylquinolinium; acridine vs. N-methylacridinium; neutral red vs. neutral red H+) the affinities of which differ by up to 380-fold. We demonstrate that the high affinity of 1 toward methylene blue (K-a = 3.92 x 10(7) M-1; K-d = 25 nm) allows for the selective sequestration and destaining of U87 cells stained with methylene blue.