A large, covalent macrocycle that can be served as an artificial allosteric model was prepared in a reasonable yield (36%) through the template-directed synthesis. The macrocycle contains two topologically discrete subcavities, each of which consists of four amide NHs of pyridine-2,6-dicarboxamide units. The macrocycle strongly binds two molecules of N,N,N′,N′-tetramethylterephthalamide in positive cooperative manner by hydrogen-bonding interactions. The association constants were calculated to be K1 = 1480 ± 90 and K2 = 5580 ± 150 M−1 with the Hill coefficient (h) of 1.6 at 25 °C in CDCl3.
Jeong, K-S., Chang, K-J., & Jang, H-Y. (2006). Synthesis and binding properties of a macrocycle with two binding subcavities. Tetrahedron Letters, 47(25), 4141-4144. https://doi.org/10.1016/j.tetlet.2006.04.078