Interaction Mechanism Of Cyclodextrins And Natural Polyphenols

Polyphenols are secondary metabolites of plants,which possess strong bioactivities and low toxicity.However,their poor water solubility and stability limit their widespread application in functional foods and medicines.For the high safety requirements,the strategy preparing polyphenol derivatives by chemical and enzymatic modifications is not suitable for the contemporary food and medicine industry.Whereas,it is a feasible way to increase the aqueous solubility and stability of polyphenols by fabricating their inclusion complexes with cyclodextrins(CDs).At present,there is a lack of systematic study on the interaction between polyphenols and CDs.In view of this,we selected some polyphenols typical structures and outstanding bioactivities.Their interaction rules with CDs were systematically investigated.Based on the experimental results,molecular docking,our Own N-layer integrated orbital molecular mechanics(ONIOM)calculation,natural bond orbital(NBO)analysis and other theoretical methods are used to clarify the interaction mechansim between polyphenols and CDs.The main research contents and results of this study are as follows:(1)The binding capacities of eight flavonoids with four common CDs were studied by phase solubility method.It was found that the volume of flavonoids and cavity size of CDs had a significant effect on the interaction.Flavonoid could form the stable complexes with both ?-cyclodextrin(?-CD)and 6-O-?-D-maltosyl-?-cyclodextrin(M-?-CD).Then,we focused on the interaction of representative flavonoids(dihydromyricetin and naringenin)with M-?-CD.It was found the formation of their complexes was spontaneous.During this process,flavonoids were completely dispersed in the M-?-CD matrix,and the complexes were supported by noncovalent bonds.Molecular simulations showed that the binding capacity of naringenin with M-?-CD was higher than that of dihydromyricetin,which was also in agreement with the phase solubility results.And hydrogen bonds between flavonoids and CDs also played an important role in the stability of the complex.(2)The binding performance of common CDs with six hydroxycinnamic acid derivatives were investigated.It was found that these hydroxycinnamic acid derivatives could form the stable complexes with ?-CD.Their differenc in of binding constants was attributed to the different substituents on their benzene ring.Thermodynamics experiments suggested that the binding of representative phenolic acids(ferulic acid and caffeic acid)with ?-CD were a spontaneous process driven by van der Waals force.During this process,ferulic acid and caffeic acid were completely dispersed in the ?-CD matrix,and the complexes were supported by noncovalent bonds.The results of ONIOM calculation and NBO analysis indicated that the binding capacity of caffeic acid with ?-CD was superior to that of ferulic acid,which coincided with the phase solubility results.(3)The binding performance and mechanism of common CDs with mangiferin were determined.The results of phase solubility and isothermal titration calorimetry(ITC)showed ?-CD had the highest binding capacity.Molecular docking,ONIOM calculations and independent gradient model(IGM)analysis revealed that the binding energy of ?-CD with mangiferin was lowest compared with those of ?-CD and M-?-CD,which coincided with the phase solubility and ITC results.The spectral characterization of mangiferin/?-CD complex,suggested that mangiferin was molecularly dispersed in the ?-CD matrix.By complexing with ?-CD,the antioxidant activity,anti-Hep G2 cell proliferation activity of mangiferin were signifciantly improved and the complex had better ROS scavenging activity.