Cholic acid inclusion compounds with aromatic ketone guests: Structure and reaction kinetics

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 P2(1), a = 16.790(1), b = 7.928(5), c = 12.262(3) Angstrom, beta = 114.25(2)degrees, Z = 2, D-c = 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 (3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-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 water(1,2,3) and alcohol guests(4,5,6) 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 structure(7). 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 arrangements, 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 alpha-face to alpha-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) benzene(11) and benzene derivatives,(12,13) aliphatic ketones(14) and esters(15). We have in the past considered the phases occurring during thermal decomposition of various CA inclusion compounds(7) and the different packing modes and subtle guest responsive changes in host conformation and packing occurring(15). More recently we have undertaken study of the rates and mechanisms of decomposition of CA tubulate clathrates with substituted aromatic guests(16) 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 com pound and that formed by CA with acetophenone(13) (CAACET) both with respect to rate and mechanism of reaction. Kinetic parameters are derived and presented for comparison.