Molecular clip 1 remains monomeric in water and engages in host-guest recognition processes with suitable guests. We report the Ka values for 32 1⋅guest complexes measured by 1 H 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-π 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-π 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 (Ka =3.92×107 m-1 ; Kd =25 nm) allows for the selective sequestration and destaining of U87 cells stained with methylene blue.

Department of Cell Biology and Molecular Genetics University of Maryland College Park MD 20742 USA

Department of Chemistry and Biochemistry University of Maryland College Park MD 20742 USA

Department of Chemistry and RECETOX Masaryk University Kamenice 5 625 00 Brno Czech Republic

Key Laboratory of Pesticide and Chemical Biology Ministry of Education College of Chemistry Central China Normal University Wuhan 430079 P R China

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