Conformational analysis of flavonoids: crystal and molecular structures of morin hydrate and myricetin (1:2) triphenylphosphine oxide complex

Abstract

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 AM1 molecular orbital methods. The molecular conformation of the two flavones described by the torsion angle θ[C(3)-C(2)-C(1t́)-C(2′)] between the benzopyrone and phenyl ring is −43.3° and 51.0° for molecules A and B of morin, respectively, and −37.0° for myricetin. Minimum energy conformations from AM1 molecular orbital calculations have θ values of −38.2° for morin and −27.0° for myricetin. The energy profile for rotation about θ for morin has a 28 kcal mol −1 barrier at 0° due to steric interactions between the 2′-hydroxy and the 3-hydroxy group. There are two local minima near 30 and 140°, in good agreement with structural results. The profile for myricetin has two equivalent minima near 30 and 150° 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 Å) 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.