XCage: A Tricyclic Octacationic Receptor for Perylene Diimide with Picomolar Affinity in Water

• Published in: Journal of the American Chemical Society Vol. 142; no. 6; pp. 3165 - 3173
• Main Authors: Liu, Wenqi, Bobbala, Sharan, Stern, Charlotte L, Hornick, Jessica E, Liu, Yugang, Enciso, Alan E, Scott, Evan A, Stoddart, J. Fraser
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 12.02.2020; Amer Chemical Soc
• Subjects: Cations; Chemistry; Chemistry, Multidisciplinary; Entropy; Fluorescence Resonance Energy Transfer; Fluorescent Dyes - chemistry; Imides - chemistry; Perylene - analogs & derivatives; Perylene - chemistry; Physical Sciences; Science & Technology; Substrate Specificity; Water - chemistry; FLUORESCENT; PROTEIN; DEEP; CYCLOPHANE; MOLECULAR RECOGNITION; ENERGY-TRANSFER; LIGAND; BINDING; HOST-GUEST COMPLEXES; PAIR
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/jacs.9b12982

The rational design of wholly synthetic receptors that bind active substrates with ultrahigh affinities is a challenging goal, especially in water. Here, we report the synthesis of a tricyclic octacationic cyclophane, which exhibits complementary stereoelectronic binding toward a widely used fluorescent dye, perylene diimide, with picomolar affinity in water. The ultrahigh binding affinity is sustained by a large and rigid hydrophobic binding surface, which provides a highly favorable enthalpy and a slightly positive entropy of complexation. The receptor–substrate complex shows significant improvement in optical properties, including red-shifted absorption and emission, turn-on fluorescence, and efficient energy transfer. An unusual single-excitation, dual-emission, imaging study of living cells was performed by taking advantage of a large pseudo-Stokes shift, produced by the efficient energy transfer.