Study On The Preparation And Antioxidation Of Inclusion Complexes Between Modified β-cyclodextrins With Flavonoids

Taxifolin（TFL）,quercetin（QCT）and Morin（MH）are common flavonoids in nature.Studies have shown that these flavonoids have good biological activities such as antioxidant,anti-inflammatory,antibacterial,anti-viral,anti-allergic,anti-tumor,and hypoglycemic.Especially for anti-oxidation,the special molecular structure of five hydroxyflavone,it can chelate with metal ions to block the formation of free radicals,and through the combination with a number of oxidases in the body,affecting its configuration,conformation,inhibition of enzyme activity,thereby inhibiting the formation of free radicals,so flavonoids as a natural the antioxidants thus attracted widespread attention.However,its poor water solubility,poor oral absorption,resulting in low bioavailability,greatly hindered its pharmacological effects.Polyamines and amides-modified cyclodextrins（CDs）have a special structure with hydrophobic inner and outer hydrophilic groups.Amino groups and amide groups can also increase recognition sites and increase the binding ability of cyclodextrins to guest molecules,thereby improving water solubility and bioavailable of the drug.Two kinds of polyamine modifiedβ-CDs and two novel amide bridgedβ-CDs were synthesized and twelve inclusion complexes with three kinds of flavonoids were prepared and characterized.The possible inclusion modes were inferred.UV-vis spectroscopy was used to study the water solubility and antioxidant activity of the inclusion complexes.The main work is as follows:1.Synthesis of polyamine modifiedβ-CD（H1）,propanediamine bridgingβ-CD（H2）,malonamide bridgingβ-CD（H3）,succinamide bridgingβ-CD（H4）,and characterized by ¹H NMR,MS,FT-IR.2.Synthesis of two polyamine modifiedβ-CD（H1,H2）and their inclusion complexation with TFL,QCT and MH.Characterized by ¹H NMR,SEM,XRD and FT-IR.According to the ¹H NMR and 2D ROESY spectra,the possible inclusion modes were infered.Using UV spectroscopy,host can form 1:1 inclusion complexes with guest,and the stability constant was further determined.The order of the stability constants is:KH2/MH>KH2/TFL>KH2/QCT>KH1/MH>KH1/TFL>KH1/QCT.The relationship between host-guest size and shape matching and the effect of hydrogen bonding interaction on the stability of inclusion complexes were discussed.3.Six novel inclusion complexes of amide-bridgedβ-CD（H3,H4）with TFL,QCT and MH were prepared and characterized by ¹H NMR,SEM,XRD and FT-IR.According to the ¹H NMR and 2D ROESY spectra,the possible inclusion modes were deduced.Using UV spectroscopy,the inclusion of host and guest was determined in a ratio of 1:1,and the stability constant was further determined.The order of the stability constants of all twelve inclusion complexes is:K_H4/MH>KH4/TFL>KH4/QCT>KH3/MH>KH3/TFL>KH3/QCT>KH2/MH>KH2/TFL>KH2/QCT>K_H1/MH>K_H1/TFL>K_H1/QCT.The mechanism of host-guest recognition is discussed in terms of size matching of host-guest and contribution of several weak interaction forces.4.The water solubility of TFL,QCT,MH and its twelve inclusion complexes was measured by the saturated aqueous solution method,and calculate the inclusion ability and inclusion efficiency of the inclusion complex.The experimental results showed that the guest molecule formed a clathrate compound and its water solubility increased by 76-254 times,its solubilization order is consistent with its stability result.The DPPH free radical scavenging assay was used to detect the changes in antioxidant activity of TFL,QCT and MH and their twelve inclusion complexes.It was found that all three flavonoids showed good antioxidant activity after inclusion complex formation,among the H1-4/TFL inclusion complexes,compared with TFL,the ability to scavenge free radicals is very obvious and can reach 60-70%.H2-4/MH inclusion complexes,compared with MH,have significantly increased antioxidant activity in the presence of increased water solubility.