Synthesis and structural characteristics of lithocholate triads: steroid-type channels occupied by spacer fragments

Abstract

Reported in this paper are the syntheses and X-ray investigations of C 2 symmetrical molecular A—B—A triads consisting of two steroid units (lithocholic acid or its methyl ester) joined together by linkers derived from bifunctional molecules such as terephthalic acid or N,N′-dicarboxypiperazine. Unlike their monomeric analogues, some of these compounds form inclusion complexes. All steroidal triads form crystals that are highly pseudo-centrosymmetric, in which the constituting molecules are held together either exclusively by van der Waals forces or form lattice inclusion complexes, with guest molecules hydrogen bonded to the host. The presence of carboxyl groups promotes the inclusion of pyridine molecules and the formation of the well known carboxylic acid...pyridine hydrogen bonds. Combined with pairwise face-to-face π-stacking between pyridine rings, these hydrogen-bond interactions lead to the formation of extended supramolecular tapes, analogous to polymers. The co-crystals of pyridine and a lithocholic acid triad undergo a symmetry-lowering phase transition from a P1 cell with Z = 1 to a P1 cell with Z = 2. The two structures are virtually the same, the two independent molecules in the larger cell being related by pseudo-translation. Changes in the type of spacer between two methyl lithocholate units from planar aromatic (terephthalic acid) to highly puckered aliphatic six-membered ring (N,N′-dicarboxypiperazine) bring about inclusion properties and changes in side-chain conformation in a crystal. Although the efficient packing of these highly elongated molecules is hindered, as indicated by low values of crystal density, ranging from 1.16 to 1.19 g cm−3, several very short C...O and H...H contacts are present in the crystals.