A Standard Structure for Bile Acids and Derivatives

Abstract

Abstract:The crystal structures of two ester compounds (a monomer in its methyl ester form, with an amino isophthalic group, and a dimer in which the two steroid units are linked by a urea bridge recrystallized from ethyl acetate/methanol) derived from cholic acid are described. Average bond lengths and bond angles from the crystal structures of 26 monomers and four dimers (some of them in several solvents) of bile acids and esters (and derivatives) are used for proposing a standard steroid nucleus. The hydrogen bond network and conformation of the lateral chain are also discussed. This standard structure was used to compare with the structures of both progesterone and cholesterol.

Crystal Structure of a Cationic Bile Salt Derivative ([3β,5β,7α,12α]-3-(2-naphthyloylamino)-7,12-dihydroxycholan-24-triethylammonium iodide)

“…The compound crystallizes free of solvents in the orthorhombic space group P2 1 2 1 2 1 with four molecules in the unit cell. The geometry of the steroid nucleus agrees well with that of the standard steroid recently proposed [3]. This standard steroid has been obtained from the data of bond lengths and the angles corresponding to the steroid nucleus in the crystal structures of 30 bile acids and esters (and substituted derivatives).…”

“…The value of the phase angle (∆ = 12.1 • ) is indicative of a conformation close to the half-chair for the D ring. The angle between the horizontal (C1, C5-C17, and C20 carbon atoms) and vertical (C3, C10, C13, C17, C18, and C19 carbon atoms) planes of the molecule [24] is 88.2 • (88.2 ± 0.5 • for the standard steroid [3]).…”

“…Their behaviors as surfactants in aqueous solutions have extensively been studied for some decades [2]. Many derivatives [3] which often modify the hydrophobic-hydrophilic balance through the insertion of substituents in the positions of the hydroxy groups of the original steroids have also been synthesized. In these derivatives, the carboxylic acid function of the side chain is preserved, although this chain has been sometimes lengthened or shortened [4].…”

“…The analysis of the steroid structures in the solid state provides information about the spatial arrangement, topology and geometry of cavities, and intermolecular interactions, therefore it, plays a key role in the understanding of recognition and binding to receptors. Crystal structures of bile acids and derivatives have been studied in detail [3,19,20]. In a much smaller number, crystal structures of anionic bile salts have been reported on, while the lack of these studies for cationic bile salts is notorious.…”

“…In this paper, we analyze the crystal structure of the iodide salt of a quaternary ammonium derivative of cholic acid having a naphthalene group attached to the 3 rd position of the steroid nucleus through an amide bond ([3β,5β,7α,12α]-3-(2-naphthyloylamino)-7,12-dihydroxycholan-24-triethylammonium iodide, 1, Figure 1a). The back (hydrophobic)-belly (hydrophilic), head (naphthyloyl moiety)-tail (quaternary ammonium group) and right-left (where, respectively, lie the O12 and O7 hydroxy groups) structure confers a three-axial chirality to the compound (Figure 1b) [3,19,20]. In addition, to covering the lack of information about these cationic derivatives, here presented results could contribute to the understanding of the supramolecular organization of the compound in an aqueous solution [6], and may be a preliminary step in the study of recognition and binding to receptors of these type of bile acid derivatives.…”