Synthesis and anion recognition characteristics of a trapezoidal benzene cage

Abstract

The molecular recognition pockets of functional biomacromolecules typically have complex spatial geometries. Creating low symmetry cage molecules, which are different from traditional ones with highly symmetrical geometries, can increase the complexity of the spatial distribution of molecular recognition sites, thus endowing the cages with new properties. However, producing cages with lower symmetry generates structural isomers, and obtaining unambiguous structural evidence to distinguish them represents a great challenge. In this contribution, we present a [2 + 2] (meta + ortho) cyclization synthetic approach for exclusively producing a trapezoidal benzene cage (1). The cage is composed of two cap (tetramethylbenzene) and four tether (isophthalamide) sections, resulting in the formation of an irregular hexahedron with the surrounding four trapezoidal faces standing alternately up and down. To the best of our knowledge, this is the first benzene cage with a trapezoidal body geometry. Taking fourteen anions including monoatomic anions, oxyanions and carboxylate anions as examples, the anion recognition characteristics of 1 in THF are demonstrated. Through NMR and mass spectrometry studies, we reveal that, depending on the size of the anion, 1 can form 1 : 1 and/or 1 : 2 host–guest complexes. Through 2D NMR and computational studies, the conformational preference of 1 when binding to anions with different geometries is disclosed. Fluorescence and NMR titration studies show that 1 has a higher affinity for anions with larger size, tetrahedral geometry, and higher electron density, resulting in an extremely high binding affinity for SO₄²⁻ (K_1:1 ∼ 10⁹ M⁻¹). In addition, 1 also shows a high binding affinity for basic anions, such as the carboxylate anion AcO^- (K_1:1 ∼ 10⁸ M⁻¹). The exemplified anion recognition is only one aspect of the properties of 1, and we believe that, with this novel trapezoidal body geometry, more unique features will be discovered in the future.