Crystalline Molecular Cleft Clathrates

A rigid bis(urea) molecular cleft (BU1) based on the cis diastereomer of a rigid isophorone-derived spacer forms solid-state inclusion complexes with a range of small molecular guests. Larger guests can be accommodated by a shift in orientation to open up crystalline channels while retaining the same overall hydrogen-bonded topology. The introduction of molecular flexibility to give BU2, which possesses a methylene spacer, destroys the host-guest complexation behavior and restores the more conventional urea alpha-tape packing, giving viscous solutions due to columnar aggregation. Crystallization of both BU1 and BU2 from a mixture of cis and trans diastereomeric forms is highly diastereoselective with the cis isomers being significantly less soluble. Isolation of a trans isomer of BU2 from crystallization of cis-depleted mother liquor reveals an unusual intramolecular hydrogen bond arrangement, explaining its greater solubility.