Water-soluble macrocyclic receptors for small neutral guests

Abstract

Two new water-soluble dicationic spiro-cyclophanes, 1 and 2, with CH₂ and (CH₂)₂ links between phenolic oxygens, have been prepared and characterised crystallographically. The binding properties of these cyclophanes have been compared with those of seven other water-soluble macrocycles: Diederich-type cyclophanes with (CH₂)₃ and (CH₂)₄ links, (3 and 4), Stoddart's cyclophane (5), α-cyclodextrin (6a), 2,6-dimethyl-α-cyclodextrin (6b), 2,3,6-trimethyl-α-cyclodextrin (6c) and β-cyclodextrin (7). The affinities of all nine macrocycles for 1,6-hexanediol (8) and hexa-2,4-diyne-1,6-diol (9) in D₂O were investigated by ¹H NMR. The strongest binding was observed between 9 and 2,6-dimethyl-α-cyclodextrin (6b) (K=1.2×10³M^-1). The alkyne diol 9 also forms a 1:2 complex with β-cyclodextrin (7) (K₁=18 M^-1, K₂=4 M^-1). The small cyclophanes 1 and 2 exhibit very little affinity for these hydrophobic guests. This unexpected finding was explained by an analysis of their crystal structures: 1 has an open cavity with an internal van der Waals radius of ca. 1.2–1.7 Å; it binds nitromethane and ethyl acetate in the solid state by C–H···π interactions, but is slightly too narrow to accommodate an alkyne, and 2 has a collapsed cavity.