Cholic Acid Inclusion Compounds with Aromatic Ketone Guests: Structure and Reaction Kinetics

Abstract

The crystal structure of the inclusion compound formed with host cholic acid and guest propiophenone indicates different packing from that seen in other CA·aromatic guest compounds. Space group P21, a = 16.790(1), b = 7.928(5), c = 12.262(3) Å, β = 114.25(2)°, Z = 2, Dc = 1.211 g.cm−3, R = 0.0515 for 2145 independent reflections. The kinetics of decomposition of the inclusion compounds of the inclusion compounds of CA with acetophenone and propiophenone are presented and mechanism and rate of decomposition compared and contrasted. The steroidal bile acid (3α, 7α, 12α-trihydroxy-5β-cholan-24-oic acid), commonly known as cholic acid (CA), forms inclusion compounds with a wide range of guest molecules. The crystal structures of the inclusion compounds with water1,2,3 and alcohol guests4,5,6 exhibit extensive host-host and host-guest hydrogen bonding. The inclusion compound of CA with acetone and three water molecules is comprised of hydrogen bonded bilayers of host and guest which pack together resulting in a close packed structure7. All water molecules and host and guest hydroxyl and carbonyl groups are involved in intermolecular hydrogen bonds of which there are ten per asymmetric unit. Apart from the above examples and an interesting structure of CA with m-fluoro-aniline, which exhibits an unusual 1:2 host:guest ratio and peculiar packing arrangement8, most CA inclusion compounds form tubulate clathrate type structures. Puckered host steroid bilayers pack together such that channels are formed in which the guest molecules are trapped without benefit of short range host-guest interactions. Bilayers result from the head to tail and α-face to α-face hydrogen bonding of the host while adjacent bilayers are bound by van der Waals forces. Guest molecules included in such fashion encompass lactones,9,10 benzene11 and benzene derivatives,12,13 aliphatic ketones14 and esters15. We have in the past considered the phases occurring during thermal decomposition of various CA inclusion compounds7 and the different packing modes and subtle guest responsive changes in host conformation and packing occurring15. More recently we have undertaken study of the rates and mechanisms of decomposition of CA tubulate clathrates with substituted aromatic guests16 as well as investigated the solid state reactivity of CA and its O(28) methyl ester, methyl cholate (MC)17. We now present the crystal structure of the 1:1 inclusion compound formed by CA with propiophenone (CAPR) and consider the complex thermal decomposition modes of this compound and that formed by CA with acetophenone13 (CAACET) both with respec to rate and mechanism of reaction. Kinetic parameters are derived and presented for comparison.