We report the synthesis of the conformationally mobile S-shaped glycoluril pentamer building block 3a and two new acyclic CB[n]-type receptors P1 and P2. P1 (9 mM) and P2 (11 mM) have moderate aqueous solubility but their host•guest complexes are poorly soluble. Host P1 does not undergo intermolecular self-association whereas P2 does (Ks = 189±27 M-1). 1H NMR titrations show that P1 and P2 are poor hosts toward hydrophobic (di)cations 6 - 11 (P1: Ka = 375-1400 M-1; P2: Ka = 1950-19800 M-1) compared to Tet1 and Tet2 (Tet1: Ka = 3.09 × 106 to 4.69 × 108 M-1; Tet2: Ka = 4.59 × 108 to 1.30 × 1010 M-1). Molecular modelling shows that P1 and P2 exist as a mixture of three different conformers due to the two S-shaped methylene bridged glycoluril dimer subunits that each possess two different conformations. The lowest energy conformers of P1 and P2 do not feature a well-defined central cavity. In the presence of guests, P2 adapts its conformation to form 1:1 P2•guest complexes; the binding free energy pays the energetic price of conformer selection. This energetically unfavorable conformer selection results in significantly decreased Ka values of P1 and P2 compared to Tet1 and Tet2.
Keywords: acyclic cucurbituril; foldamer; isothermal titration calorimetry; molecular recognition.