Molecular structure and activity toward DNA of baicalein, a flavone constituent of the Asian herbal medicine "Sho-saiko-to"

Baicalein (5,6,7-trihydroxyflavone, 1) is of interest because of its broad spectrum of biological activity. It is a constituent of the east Asian herb al remedy, "Sho-saiko-to". The 3D structure of 1 was determined using X-ray diffraction. The compound exists in an almost planar conformation with a C -2-C-1' bond distance of 1.476(5) Angstrom. Hydrogen-bonding interactions p redominate in the crystal structure. The position of the three hydroxyl gro ups maximizes intramolecular hydrogen bonding, and each of the hydroxyl hyd rogen atoms is a donor in a three-center hydrogen bond. The carbonyl oxygen , O-4, is an acceptor in an intramolecular hydrogen bond (with OH-5). Two m olecules of 1 exist as hydrogen-bonded dimers related by inversion center ( -x + 1, -y, -z + 1). 0-4 is also an acceptor in an intermolecular hydrogen bond with OH-6. The planarity of the flavone framework is dependent on stru ctural and/or electronic forces that stabilize the negative charge on the e xocyclic oxygen atom, 0-4. Compound i, therefore, is planar in any situatio n where forces can stabilize the negative charge on 0-4. Consistent with th is, UV absorbance studies performed on 1-DNA complexes with varying concent rations of 1 strongly suggest intercalation of 1 within the double helix, f ollowed by possible interstrand cross-links.