Systematic Structural Study of Asymmetric Supramolecular Assembly by a Series of Bile Acid Derivatives with Different Side-Chain Lengths

A systematic structural study of asymmetric supramolecular assembly in the crystalline state has
been performed by one-by-one insertions of methylene spacers into the side-chain of steroidal bile acids. Five
derivatives of bile acid with different side-chain lengths, bisnorcholic acid (0), norcholic acid (1), cholic acid (2),
homocholic acid (3), and bishomocholic acid (4), were recrystallized from many solvents. X-ray diffraction studies of
the resulting crystals revealed that these derivatives form various bilayer and layerlike structures in which two
steroidal planes are diversely aggregated by using the hydrophilic faces inside. Such asymmetric bimolecular
aggregation modes are logically classified into 10 categories on the basis of the relative positions between two steroidal
planes. Actually, four modes among them were observed by means of one-by-one methylene insertions. This is
attributable to the fact that four hydrogen-bonding groups, three hydroxyl groups on the skeletons and one carboxyl
group at the side-chain, work cooperatively to form various hydrogen-bonding networks with the corresponding
host frameworks. In this way, the insertion of methylene spacers plays a decisive role to diversify the asymmetric
bimolecular aggregation modes.