Cholic Acid Inclusion Compounds with Aromatic Guests: Structures and Decomposition Kinetics

Abstract

Cholic acid forms 1:1 (host:guest) inclusion compounds with a variety of aromatic guest molecules. The crystal structures of the inclusion compounds with benzonitrile and p-nitro toluene have been elucidated. CA·benzonitrile: space group p21, a = 13.642(3), b = 8.133(2), c = 14.055(3) Å, β = 114.12(2)°, Z = 2, Dc = 1.194 g.cm−3, final R factor = 0.0781 for 1853 independent reflections. CA·p-nitro toluene: space group P21, a = 13.495(1), b = 8.266(4), c = 14.398(2) Å, β = 114.61(1)°, Z = 2, Dc = 1.249 g.cm−3, final R factor = 0.0608 for 2783 independent reflections. The kinetics of decomposition of these and related compounds are investigated and kinetic parametesrs Ea and In A so derived compared and contrasted. 3α, 7α, 12α-trihydroxy-5β-cholan-24-oic acid or Cholic acid (CA) has been shown to form inclusion compounds with a variety of guest molecules. The 1:1 inclusion compounds with methanol, ethanol and n-propanol1,2,3 exhibit extensive host-host and hostguest hydrogen bonding and the guest molecules are accommodated in cavities. The structures of the hydrate4 and hemihydrate5,6 are composed of hydrogenbonded bilayers and helical columns respectively while the inclusion compound with acetone and three water molecules7 is composed of bilayers of host and guest hydrogen bonded together in a system containing ten unique hydrogen bonds. The bulk of CA inclusion compounds crystallise as tubulate clathrates in which host molecules are hydrogen bonded together in a head to tail fashion to form puckered bilayers with the hydrophobic β faces exposed on the bilayer surfaces. These bilayers are in turn packed such that channels remain between them in which guest molecules are stacked in columns parallel to the b crystallographic direction. Guest molecules such as aliphatic ketones8, lactones9, aliphatic10 and vinyl esters as well as the aromatic guests nitrobenzene, aniline11, acetophenone12 and benzene13 are included in this manner. Given the similarities in the structures of these compounds we decided to investigate the kinetics of decomposition with the aim of relating reactivity to structure at a molecular level. The kinetics of decomposition of a variety of inorganic salts and hydrates have been extensively studied14,15,16 and the effects of changes in reaction conditions, particle size and sample pretreatment investigated.17,18,19 The decomposition kinetics of solid organic clathrates has not been considered in spite of the potential insights into stability and host-guest interactions to be gained therefrom. We present the decomposition kinetics of a group of CA inclusion compounds with the aromatic guest molecules benzonitrile (CABN), aniline (CAAN), nitrobenzene (CANI), p-nitro-toluene (CAPNOT) and p-toluidine (CAPTOL). Possible mechanisms for the decomposition reaction are advanced and the crystal structures of CA with benzonitrile and p-nitro-toluene guests are presented while those of the other inclusion compounds included in this study have been published elsewhere.11,20