Macrocycles with two exclusive hydrogen-bonding modes

A series of large, 44-membered macrocycles 7a-e were synthesized and characterized, which display two different diagonal binding modes. The unsubstituted macrocycle 7a strongly binds naphthalene-2,6-dicarboxylate through hydrogen bonds with the association constant (K_a ± 15%) of 4500 M^-1 in 40% (v/v) CD₃CN/CDCl₃ at 23 ± 1 °C. Introduction of an electron-withdrawing substituent (Cl) at all four corners increases the binding affinity (22,000 M^-1 for 7b), while that of an electron-donating substituent (pyrrolidinyl) greatly decreases it (150 M^-1 for 7c). The same propensity has been observed with macrocycles 7d and 7e bearing different substituents at two diagonal corners, suggesting that the relative population of the binding modes would be modulated by controlling the electron density of the aromatic ring.