Importance of weak hydrogen bonds in the formation of cholamide inclusion crystals with aromatic guests

Steroidal cholamide (CAM) has been found to form inclusion crystals with 23 aromatic compounds in 1:1 and 2:1 host-to-guest molar ratios. The 1:1 crystals have guest-dependent host frameworks, termed beta-trans-type, where weak hydrogen bonds such as N-H center dot center dot center dot pi, C-H center dot center dot center dot pi, and C-H center dot center dot center dot O play a key role in linking the host and guest molecules. The steroidal side-chains involving methyl, methylene, and amide groups serve as the hydrogen bond donors, and aromatic guest molecules serve as the acceptors. Three kinds of such weak hydrogen bonds are visualized by the Hirshfeld surfaces of the guest molecules. Comparisons of the inclusion crystals of CAM and cholic acid (CA) with the same guests clarify a profound effect of the weak hydrogen bonds. In the case of the 1:1 crystals, the N-H center dot center dot center dot pi hydrogen bonds explain the fact that CAM always employs the beta-trans-type framework, while CA employs either an alpha-gauche- or beta-trans-type framework. On the other hand, the 2:1 crystals, termed DCA-type, have only C-H center dot center dot center dot pi hydrogen bonds. The guest-dependent isomerization of these frameworks is examined in terms of the weak hydrogen bonds as well as compatibilities in size and shape.