Synthesis, Characterization And Bioactivity Evaluation Of Rare Earth Complexes With Phloretin, Phloretin-Isonicotinoyl Hydrazone

Phloretin, which is an active substance, contained in dihydrochalcone, mainly present in apples, pears and other fruits or vegetables juices.At present, phloretin is used as a new type of cosmetic additives in foreign countries, because phloretin may dilute the stain, whitening skin and the effect is better than the present commonly used arbutin and kojic acid in cosmetics. In addition, phloretin posses lots of biological activities. Antioxidant, anti-tumor, reducing blood sugar, protecting blood vessels has been reported. Currently, the research on phloretin is mainly focused on the activity; the field on the chemical modification is still not fully open up. Nowadays, coordination chemistry of natural medicine has become a hot point in drug research and development, previous work suggests that when the metal element and coordinated with organic ligand, complexes may posses increasing efficacy, and even generate new pharmacological activites. Research involving flavonoids, flavonols, isoflavone, etc, chalcone is not common. In this paper we choose phloretin as a ligand, and synthesised a novel ligand with isoniazid hydrazone, and then coordinated with rare earth (La, Nd, Pr, Sm) respectively. We hope to improve the biological activity of phloretin through chemical modification. and provide a theoretical basis to the structure research of phloretin. This thesis consists of five parts:Chapter one, reviews the international research status of phloretin, and then take a brief introduction of biological function of hydrazone compounds and flavonoid complex, clarify the direction and significance of this research.Chapter two, selected representative lanthanide elements-La (Ⅲ), Nd (Ⅲ), Pr (Ⅲ), Sm (Ⅲ) corresponding with phloretin, synthesized four rare earth complexes, and then characterized by using elements analysis, infrared spectroscopy and thermal analysis, and infered structures of the phloretin rare earth complexes.Chapter three, selected isoniazid, which is the preferred drug in treatment of tuberculosis, under suitable conditions, synthesized isonicotinoyl hydrazone with phloretin, characterized by using ultraviolet spectroscopy, infrared spectroscopy, elemental analysis,1H NMR,13C NMR. Then we choose the hydrazone as a ligand, coordinated with La (Ⅲ), Nd (Ⅲ), Pr (Ⅲ), Sm (Ⅲ) synthesized four Hydrazone Complexes, characterized by elemental analysis, infrared spectroscopy and thermal analysis and infered structures of the hydrazone rare earth complexes.Chapter four, the antioxidant activity of phloretin, phloretin isonicotinoyl hydrazone and the eight rare earth complexes were measured, and studied the complexes interactions with bovine serum albumin (BSA) by fluorescence spectroscopy. The antioxidant experiment including reduction of Fe3+ ability, scavening OH-radicals, DPPH radical and ABTS radical ability and inhibition of lipid peroxidation. The results show that ligands and complexes exhibit different activities in different experimental models. In the reducing Fe3+ experiment, the activities of the complexes were higher than the corresponding ligands, and complexes of hydrazone reduction were significantly higher than phloretin complexes. In the OH radical scavening assay, the scavenging ability of the complex ligands were increased to varying degrees, excepting hydrazone-Pr complexes. In clear DPPH, ABTS radicals and inhibiting lipid peroxidation experiments, the ability of the complexes showed lower than those of the ligands, not improved. Fluorescence spectroscopy experiments showed that the eight rare earth metal complexes can interact with the BSA and the fluorescence quenching of BSA are due to the formation of static quenching, and the mode of action of BSA are hydrogen bonds and van der Waals force Lord.