Importance of Weak Hydrogen Bonds in the Formation of Cholamide Inclusion Crystals with Aromatic Guests

Abstract

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 β-trans-type, where weak hydrogen bonds such as N-H • • • π, C-H • • • π, and C-H • • • O play a key role in linking the host and guest molecules. The steroidal sidechains 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 • • • π hydrogen bonds explain the fact that CAM always employs the β-trans-type framework, while CA employs either an R-gaucheor β-trans-type framework. On the other hand, the 2:1 crystals, termed DCA-type, have only C-H • • • π 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.

Flexible host frameworks with diverse cavities in inclusion crystals of bile acids and their derivatives

“…As in the case of CA, the former and the latter structures have the 0‐D cavity for smaller guests and the 1‐D cavity for larger guests, respectively. Cholamide (CAM), which has an amide group at the side chain, forms a bilayer structure with the 1‐D cavity, in which 80 or more guests are included 14. The high inclusion ability is attributed to the bilayer structure, which is classified into five subtypes identical to those of CA.…”

“…65%) to employ the α‐gauche, α‐trans, or β‐gauche types in the bilayer structure at a 1 : 1 host/guest ratio or the sandwich structure at a 1 : 2 ratio. However, only four isomers out of 18 select these host frameworks, and the others select the 1 : 1 β‐trans or 2 : 1 parallel type in the bilayer structure 14a. Remarkably, four o ‐isomers select the parallel type of lower PCcavity in a range of 46–53%.…”

“…The data in Table 1 also exhibit that the same guest is not necessarily included in the same host framework of CA and CAM, though these two hosts can form very similar host cavities in size and shape in the bilayer structures. Such different formation of the host frameworks is attributed to their functional groups, carboxylic acid and amide groups, which lead to different host–guest interactions in their cavities 14. For example, Figure 5 shows hydrogen bond networks in β‐trans type in CA and CAM crystals with m ‐chlorotoluene.…”

“…In the CAM crystal, one additional bond is observed: NH/π bond (IV) is located between one NH donor of the amide group of the side chain and the phenyl ring of the guest molecule. This NH/π bond enables CAM to preferentially form the β‐trans type for many aromatic guests, because other types prevent the NH/π bond formation owing to the repulsive position of the host molecules and aromatic guest molecules 14a. In the case of CA crystals without NH/π bond, size and shape fit through CH/π or CH/O bonds would be more important.…”

“…The difference in the host–guest interactions in CA and CAM crystals causes contrasting guest inclusion. The NH donor of CAM interacts with the acceptor of polar guests to form host–guest hydrogen bond networks, resulting in the inclusion of over 50 alcohols in CAM bilayer structure 14b. On the contrary, CA includes many nonpolar guests that are not included in CAM cavity, and includes only two alcohols in the bilayer structure.…”