Anion Transporters Based on Noncovalent Balance Including Anion-π, Hydrogen, and Halogen Bonding

Anion transmembrane transport mediated by novel noncovalent interactions is of central interest in supramolecular chemistry. In this work, a series of oxacalix[2]arene[2]triazine-derived transporters and bearing anion-π-, hydrogen-, and halogen-bonding sites in rational proximity were designed and synthesized by a one-pot strategy starting from gallic acid ester derivatives and mono- or di-halogen-substituted triazines. H NMR titrations demonstrated efficient binding of and toward Cl and Br in solution, giving association constants in the range of 10-10 M. Cooperation of anion-π, hydrogen, and halogen bonding was revealed as a driving force for anion binding by single-crystal structures of two complexes and density functional theory calculations. Fluorescence assays indicated that compounds are efficient chloride transporters with effective concentrations (EC) falling in the range of 3.1-7.4 μM and following an order of > > > . The contribution of halogen bonding and cooperative noncovalent bonds to ion transport was then discussed. Significantly, transporters exhibit high anticancer activity. In the presence of and KCl (60 mM), the cell survival of HCT116 reduces to 11.9-24.9% with IC values in the range of 52.3-66.4 μM.