Water-soluble macrocyclic receptors for small neutral guests

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), alpha-cyclodextrin (6a), 2,6-dimethyl-alpha-cyclodextrin (6b), 2,3,6-trimethyl-alpha-cyclodextrin (6c) and beta-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 H-1 NMR. The strongest binding was observed between 9 and 2,6-dimethyl-alpha-cyclodextrin (6b) (K = 1.2 x 10(3) M-1). The alkyne diol 9 also forms a 1 :2 complex with beta-cyclodextrin (7) (K-1 = 18 M-1, K-2 = 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 Angstrom; it binds nitromethane and ethyl acetate in the solid state by C-H ...pi interactions, but is slightly too narrow to accommodate an alkyne, and 2 has a collapsed cavity.