Molecular tweezers and clips as synthetic receptors. Molecular recognition and dynamics in receptor-substrate complexes

Abstract

The molecular tweezers (1, 2) and clips (3-7) containing naphthalene and benzene spacer units can be synthesized via repetitive Diels-Alder reactions by the use of a molecular "Lego" set consisting of bisdienophiles (8, 9, 14) and dienes (10, 13). The new receptors selectively bind electron-deficient neutral and cationic substrates in solution. Only the benzene-spaced tweezers form complexes with aliphatic substrates, whereas the other receptors bind aromatic substrates preferentially. HPLC studies with 1 and 2 chemically bonded to stationary phases give similar results for the heterogeneous systems. The formation of stable complexes between the water-soluble clip 5g and N-alkylpyridinium cations, such as N-methylnicotinamide and NAD(+), in aqueous solution illustrates the importance of the hydrophobic effect for arene-arene interactions. The dynamics of the complex formation and substrate mobility were investigated by the use of temperature-dependent liquid- and solid-state NMR spectroscopy. The electrostatic potential surface (EPS) of 1-7 is calculated to be surprisingly negative on the concave side of each molecule and, hence, complementary to the EPS of the electron-deficient substrates, suggesting that the attractive receptor-substrate interaction is here of predominantly electrostatic nature.