Crystalline Molecular\nCleft Clathrates

A rigid bis(urea) molecular cleft (<b>BU1</b>)\nbased on the <i>cis</i> diastereomer of a rigid isophorone-derived\nspacer forms\nsolid-state inclusion complexes with a range of small molecular guests.\nLarger guests can be accommodated by a shift in orientation to open\nup crystalline channels while retaining the same overall hydrogen-bonded\ntopology. The introduction of molecular flexibility to give <b>BU2</b>, which possesses a methylene spacer, destroys the host–guest\ncomplexation behavior and restores the more conventional urea α-tape\npacking, giving viscous solutions due to columnar aggregation. Crystallization\nof both <b>BU1</b> and <b>BU2</b> from a mixture of <i>cis</i> and <i>trans</i> diastereomeric forms is highly\ndiastereoselective with the <i>cis</i> isomers being significantly\nless soluble. Isolation of a <i>trans</i> isomer of <b>BU2</b> from crystallization of <i>cis</i>-depleted\nmother liquor reveals an unusual intramolecular hydrogen bond arrangement,\nexplaining its greater solubility.