Supramolecular Chirality in Crystalline Assemblies of Bile Acids and Their Derivatives; Three-Axial, Tilt, Helical, and Bundle Chirality

Abstract

Abstract:Steroidal bile acids and their derivatives exhibit characteristic inclusion behaviors in the crystalline state. Their crystals present varied assemblies due to asymmetric molecular structures, which relate to supramolecular properties through cooperative weak interactions. An overview indicates that the steroidal assemblies lie in an intermediate position among various molecules and have hierarchical structures such as primary, secondary, tertiary, and host-guest assemblies like proteins. Such an interpretation brought about the idea that the assemblies with dimensionality present supramolecular chirality such as three-axial, tilt, helical, bundle, and complementary chirality. This concept of the supramolecular chirality enables us to understand formation of chiral crystals starting from the molecular chirality of the steroidal molecules.

Structural studies on lithocholyl-N-(2-aminoethyl)amide in the solid state

“…For instance, N-substituted amides of lithocholic acid and derivatives of 3a-hydroxy-24-amino-5b-cholane have shown in vitro activity against Gram positive strains and mycetes [14]. Bile acids and steroids exhibit variable crystal structures, solvates, and co-crystals [15][16][17][18][19][20][21][22]. Although structural studies of systems involving bile acid derivatives have long been a challenge due to their complex and supramolecular nature, papers dealing with single crystal X-ray diffraction characterization of crystalline host-guest assemblies of steroidal and related molecules have been published.…”

“…Although structural studies of systems involving bile acid derivatives have long been a challenge due to their complex and supramolecular nature, papers dealing with single crystal X-ray diffraction characterization of crystalline host-guest assemblies of steroidal and related molecules have been published. The review articles by Miyata et al [17,18] for example, address the diverse structures of bile acid derivatives with the concept of hierarchy and supramolecular chirality. Single crystal X-ray diffraction is an established method in defining solid state structures of molecules [23], but preparation of single crystals suitable for single crystal X-ray crystallography of bile acid derivatives can be a rather difficult task.…”

A Standard Structure for Bile Acids and Derivatives

“…On the other hand, the ability to form hydrogen bonds by CA plus the characteristics of head-to-head dimers have been used for designing a crystal, in which a single water molecule is encapsulated between two cholic residues in an ice-like structure [17]. Miyata et al have also studied the supramolecular chirality in crystals generated from chiral [37][38][39][40] and achiral [41,42] molecules, and rationalized a hierarchical organization in BA crystals like that in proteins [3,43,44].…”

Generation of Supramolecular Chirality around Twofold Rotational or Helical Axes in Crystalline Assemblies of Achiral Components

“…Since the discovery of cholic acid inclusion compounds [1][2][3], our research has been devoted to supramolecular chirality in crystals of chiral molecules, such as steroids [4][5][6][7][8][9][10] and alkaloids [11][12][13][14][15][16][17][18]. The fascinating relations between molecules and their assemblies gradually directed us toward achiral molecules.…”