Chalcogen Bonding and Hydrophobic Effects Force Molecules into Small Spaces

Abstract

Supramolecular capsules are desirable containers for the study of molecular behavior in small spaces and offer applications in transport, catalysis, and material science. We report here the use of chalcogen bonding to form container assemblies that are stable in water. Cavitands <b>1</b>-<b>3</b> functionalized with 2,1,3-benzoselenadiazole walls were synthesized in good yield from resorcin[4]arenes. The solid-state single-crystal X-ray structure of <b>3</b> showed a dimeric assembly cemented together through multiple Se···N chalcogen bonds. Binding of hydrophobic and amphiphilic guests in D₂O was investigated by ¹H NMR methods and revealed host-guest assemblies of 1:1, 2:1, and 2:2 stoichiometries. Small guests such as <i>n</i>-hexane or cyclohexane assembled as 2:2 capsular complexes, larger guests like cyclohexane carboxylic acid or cyclodecane formed 1:1 cavitand complexes, and longer linear guests like <i>n</i>-dodecane, cyclohexane carboxylic acid anhydride, and amides created 2:1 capsular complexes. The 2:1 complex of the capsule with cyclohexane carboxylic acid anhydride was stable over 2 weeks, showing that the seam of chalcogen bonds is "waterproof". Selective uptake of cyclohexane over benzene and methyl cyclohexane over toluene was observed in aqueous solution with the capsule. Hydrophobic forces and hydrogen-bonding attractions between guest molecules such as 3-methylbutanoic acid stabilized the assemblies in the presence of the competing effects of water. The high polarizability and modest electronegativity of Se provide a capsule lining complementary to guest C-H bonds. The 2,1,3-benzoselenadiazole walls impart an unusually high magnetic anisotropy to the capsule environment, which is supported by density functional theory calculations.