The Studies Of Phosphorylation Of Daidzein And Their Interactions With Cycoldextrin

Daidzein(7, 4'-dihydroxyisoflavone) is one of the most important isoflavonoids. It has been pharmacologically shown with the effects of antiarrhythmic, resistance of hypoxia and anoxemia, relieving spasticity, and estrogen. Bioavailability by oral absorption of daidzein is low because of its poor water- and oil-solubility, which limit its clinical application. Thus, it has been the focus of research that expand its applications field by improving its water- or oil-solubility. Rencent years, the technology of preparing cyclodextrin complex has been used widely in the research and development of chinese-western drugs pharmaceutical. Now, many poorly soluble drugs have been made to cyclodextrin inclusion compound so that the physicochemical properties of drugs could be obviously improved. The application of this new technology provides an effective means of development for the pharmaceutical preparations and new dosage form.Phosphate plays an important role in biological diversity and biological activity of compounds. The introduction of phosphate ester could change the nature of the physicochemical properties of matrix so that the body's biological ability to obtain could be increased. Seven phosphorylation reagents and seven daidzein phosphorous derivatives were synthesized. All the products were characterized by IR, NMR and ESI-MS. The results showed that daidzein was reacted with seven phosphorylation reagents and C7-OH was more active than C4'-OH.The interactions of daidzein phosphorous derivatives withβ-cyclodextrin in solution were studied using fluorescence spectrometry. The fluorescence intensity of 7-(diethyl phosphoryl) daidzein acetate solution was increased with the concentration ofβ- cyclodextrin, which indicated that it has formed stable complex withβ- cyclodextrin. The inclusion ratio of theβ-CD inclusion complex calculation by the Benesi-Hildebrand equation was 1:1 and its inclusion constant was 1.75×10²(mol/L)^-1. While the fluorescence intensity of other daidzein phosphorous derivatives was decreased with the concentration ofβ- cyclodextrin, which may contribute to the higher steric hindrance of their longer chains so that they couldn't enter the hydrophobic cavity ofβ- cyclodextrin.The influences ofβ-cyclodextrin on the solubility of 7-(diethyl phosphoryl) daidzein acetate in aqueous media were measured by UV spectrometry, it was suggested that β-cyclodextrin could promote the solubility of 7-(diethyl phosphoryl) daidzein acetate. An inclusion compound ofβ-cyclodextrin with 7-(diethyl phosphoryl) daidzein acetate was prepared by the co-precipitation method. Their structure was characterized by UV and IR spectrometry, ¹H NMR, ¹³C NMR and MS. The results indicated the 1: 1 stoichiometry of inclusion complex was produced.