Study On Relation Of Molecular Structure-Bioactivity And Cooperative Action For Flavonoid Coordination Complexes

The relation of molecular structure-bioactivity and the cooperative action for Quercetin-metal coordination complexes have been researched by the theory and method of coordination chemistry in this paper.The coordination complexes were synthesized at the experimental condition optimized. Flavonoid compound, Quercetin, was selected as organic ligand, for it bears active dentates. Three metal elements, Zn( Ⅱ), Cu(Ⅱ) and Fe(Ⅲ), were used for synthesizing the complexes. Besides the temperature of reaction system and the reaction time, the pH value of reaction solution was a key factor for the form of coordination complexes. And the optimal pH ranges were pH 7.0~8.7, pH 6.0~8.5 and pH 5.0~8.0 for Quercetin- Zn(Ⅱ), Quercetin- Cu(Ⅱ) and Quercetin- Fe(Ⅲ), respectively. The Quercetin coordination complexes could be obtained at the optimized reaction conditions, viz., optimal pH range and reaction in water bath at 70℃ for 40 min. The yields of synthesizing Que- Zn(Ⅱ), Que- Cu(Ⅱ) and Que-Fe(Ⅲ) complexes were 72.5%, 68.4% and 78.2%, respectively.The structures of coordination complexes have been characterized. For the three Quercetin-metal complexes, UV-Vis absorption spectra, IR spectra and ~1HNMR spectra indicated that the chelating groups of Quercetin were 4-carbonyl and 5-hydroxyl as the most possible dentaes with metal ion to form hexatomic ring coordination complex. The potential configurations of Quercetin-metal chelate compounds have been first optimized by quantum chemistry computation forconfirming which configuration with the lowest energy. And the results of calculation showed a good consistency with the analytical data of spectrum curves.Composition or stability constants of the complexes were determined by Job method, equilibrium shift method and isosbestic point-continuous variation method. The results of analysis showed that Quercetin could chelate Zn( II), Cu( II) or Fe(III) in different mole ratios to form coordination complexes with diverse coordination number. The stability constants of the three complexes were logf32,QUe-zn = 12.2, logP2,Que-cu = 9.74, logp3iQue.Fe = 16.6, respectively.In this paper, structure-bioactivity and cooperative action for coordination complexes have been discussed through analyzing the antioxidant activity of Quercetin-metal complexes. The inhibitory effect of Quercetin and its complexes on superoxide anion free radical, (V, was tested by pyrogallol auto-oxidation system. Quercetin- Zn(II) and Quercetin- Fe(III) were more effective than Quercetin on resisting superoxide anion free radical, showing the good cooperative action between Quercetin and trace metal elements. For detecting the cleaning effects of the complexes on the hydroxyl free radical, 'OH, produced by Fenton reaction, a new photometric method based on Methylene Blue decolouration was established. Que-Zn(II), Que- Cu(II) and Que- Fe(III) complexes hold significant effects of scavenging action on "OH as shown in this study. The cooperative action of Quercetin coordination complexes on antioxidant activity was first investigated, and the result indicated that capability of resisting 02'' for the complexes had a direct relationship to the total amount of Que-metal complexes mixed in certain ratio. But the activity of cleaning up 'OH for mixture system of complexes presented a peak value phenomenon, showing a more complicated relation between antioxidant activity and total amount of the complexes.Antioxidative effect of Quercetin coordination complex was close related to its structure. Because the hyperconjugation system of Quercetin complex could make itself configuration more stabilization after giving the hydrogen or electron byfunctional phenolic hydroxy group, the complex presented more active capability than ligand itself about antioxidant activity.The speciality of surfactants had been first applied to study modification of dissolution and improvement of bioavailability for Quercetin-metal coordination complex. The critical micelle concentrations (cmc) of surfactants in the Quercetin-metal coordination complex solutions have been determined by using the method of conductance ratio. In Quercetin coordination complex solution there were two cmc values at the lower concentration area of CTAB [Ci6H33N(CH3)3Br]. And this phenomenon about two cmc points was much similar to that of natural bio-surfactant. All the CTAB, SDBS (CuJfeCeHLtSC^Na) and Tween-80 could improve the water-solubility of Quercetin complexes when the concentrations of these surfactants were above the cmc values, but only CTAB could increased the oil-solubility of these complexes. Therefore, Quercetin-metal-CTAB micelle congeries in water phase could go into the octanol phase through oil-water interface. In phospholipid reversed micellar system, the transfer efficiency of complex between the two phases was influenced by pH of water phase, and around pH7 the complexes were easy to enter the phospholipid-octanol reversed micellar phase.Phospholipid membrane was first used as mimetic biomembrane model system to determine the velocity of infiltrating biomembrane for Quercetin complexes. The change rate of the film electric potential, Em, for Quercetin coordination complex differed markedly from that of Em for Quercetin itself.It was the first time that mixture containing Quercetin, Que- Zn(II), Que-Cu( II) and Que- Fe(III) complexes could be well separated by HPLC under the conditions of methanol-water mobile phase and linear gradient elution.