CONFORMATIONAL-ANALYSIS OF FLAVONOIDS - CRYSTAL AND MOLECULAR-STRUCTURES OF MORIN HYDRATE AND MYRICETIN (1/2) TRIPHENYLPHOSPHINE OXIDE COMPLEX

The crystal and molecular structures of morin (2', 3, 4', 5. 7-pentahydroxyflavone) hydrate (I). and myricetin (3', 4', 5', 3, 5, 7-hexahydroxyflavone) triphenylphosphine oxide (TPPO) (1: 2) co-crystal complex (II) have been studied by X-ray analysis and AM 1 molecular orbital methods. The molecular conformation of the two flavones, described by the torsion angle theta [C(3)-C(2)-C(i')-C(2')] between the benzopyrone and phenyl rings is -43.4-degrees and 51.0-degrees for molecules A and B of morin, respectively, and -37.0-degrees for myricetin. Minimum energy conformations from AM 1 molecular orbital calculations have theta values of -38.2-degrees for morin and -27.0-degrees for myricetin. The energy profile for rotation about theta for morin has a 28 kcal mol-1 barrier at 0-degrees due to steric interactions between the 2'-hydroxy and the 3-hydroxy group. There are two local minima near 30 and 140-degrees, in good agreement with structural results. The profile for myricetin has two equivalent minima near 30 and 150-degrees with a barrier of less than 2 kcal mol-1. In the crystal both flavones form extensive networks of intra- and intermolecular hydrogen bonds. In (I), each morin conformer packs in alternating layers linked by water molecules, while in (II), TPPO stabilizes the crystal by formation of short hydrogen bonds (2.58 - 2.65 angstrom) of the phosphoryl oxygen to the flavone. Myricetin also forms a two dimensional sheet-like packing in which myricetin molecules hydrogen bond to each other, as well as to TPPO. These conformational and hydrogen bonding patterns provide insight into specific types of ligand receptor interactions and support structure activity data which suggest the importance of electronic and hydrogen bonding properties in the bioactivity of flavones.