Synthesis and Molecular Recognition of Water-Soluble S6-Corona[3]arene[3]pyridazines

We report the efficient and scalable synthesis and molecular-recognition properties of novel and water-soluble S6-corona[3]arene[3]pyridazines. The synthesis comprises a one-pot nucleophilic aromatic substitution reaction between diesters of 2,5-dimercaptoterephthalate and 3,6-dichlorotetrazine followed by the inverse electron-demand Diels-Alder reaction of the tetrazine moieties with an enamine and exhaustive saponification of esters. The resulting S6-corona[3]arene[3]pyridazines, which adopt a 1,3,5-alternate conformation in the crystalline state, are able to selectively form stable 1:1 complexes with dicationic guest species in water with association constants ranging from (1.10±0.06)×10(3)  M(-1) to (1.18±0.06)×10(5)  M(-1). The easy availability, large cavity size, strong and selective binding power render the water-soluble S6-corona[3]arene[3]pyridazines useful macrocyclic hosts in various disciplines of supramolecular chemistry.