Encapsulation of Linear and Cyclic Alkanes in Water Within a Dimeric Deep-Cavity Sulfonatocalix[4]arene Capsule.

The tetrasulfonated deep-cavity calix[4]arene 1, bearing a second row of benzene rings around its upper rim, self-assembles into a dimeric capsule in water upon encapsulation of small hydrophobic guests. 1H NMR spectroscopy shows that the two calixarene subunits interdigitate, creating an elongated hydrophobic cavity that accommodates linear and cyclic alkanes, as well as benzene and hexafluorobenzene. NMR competition experiments establish a guest size-dependent stability sequence: among the linear alkanes, complex stability peaks at n-hexane and decreases for both shorter and longer homologs, whereas the cycloalkane complexes become steadily more stable from cyclopentane to cyclooctane, with the cyclooctane complex outcompeting the n-octane complex. Benzene forms a comparatively stable complex that is displaced by cyclohexane and cycloheptane, while hexafluorobenzene is in turn displaced by benzene. DFT calculations (BP86-D4(COSMO = water)/def2-SVP) of substitution energies and packing coefficients reproduce these trends qualitatively, particularly for the larger guests, and rationalize the guest size dependence in terms of a shift from single- to bis-subunit CH···π contacts, and, for hexafluorobenzene, a central binding position that minimizes F···π interactions. Together, these results establish deep-cavity calix[4]arene 1 as a versatile, hydrophobic effect-driven capsule for the recognition of small apolar molecules in water.