New Synthetic Route to Water Soluble Prism[5]arene Hosts and their Molecular Recognition Properties

We report that the direct macrocyclization of naphthalene monomers (N1 and N3) bearing ethyl ester functional groups delivers prism[5]arene derivatives (H1E and H3E) which can be deprotected to yield water soluble prism[5]arenes (H1 and H3). 1H NMR spectroscopy showed that dicationic guests G1 – G9 bind with the hydrophobic cores buried inside the anisotropic magnetically shielding cavity. Isothermal titration calorimetry measurements showed that H1 and H3 are high affinity hosts in PBS buffered water with Ka values exceeding 109 M-1 for G9. The complexation events are driven by the non-classical hydrophobic effect, CH•••p interactions, and electrostatic interactions. Host H1 displays somewhat higher affinity toward a common guest than WP6 but is significantly less potent than P6AS. Nevertheless, H1 and H3 should be considered alongside other high affinity hosts for a variety of chemical and biological applications.