Construction Of Non-covalent And Covalent Cyclodextrin-resveratrol And Its Effects On Exercise Performance In Mice

Supramolecular chemistry is a discipline involving the interaction of molecules between chemistry and various disciplines.Molecules,ions or groups in supramolecular chemistry can interact through van der Waals forces,hydrogen bonds,and covalent bonds.After decades of development,supramolecular chemistry has produced many newly molecular structures.As second-generation supramoleculer,cyclodextrin has been widly used in many aspects.In previous studies,the researchers focused on the inclusion complex of cyclodextrin with small drug molecules,which could change some properties of the original drugs.However,there were some shortcomings in this method.Because cyclodextrin has many hydroxyl groups,these hydroxyl groups could react with different substituents to form novel substances through chemical bonds.In addition,the novel compound might have newly properties.Resveratrol are discovered from the natural plant,such as veratrum album and polygonum cuspidatum.Since the researchers found the resveratrol have a well anti-fatigue effect,its research enthusiasm has not decreased.But resveratrol has low water solubility,which limits its application in many aspects.The main contents of this paper are as follows:First,this part mainly introduced the preliminary study on the synthesis and properties of cyclodextrin-resveratrol derivatives.(1)Taking ?-cyclodextrin and its derivative as host molecules,and resveratrol as guest molecule.We used freeze-drying method to synthesize a corresponding series of inclusion complexes.The particularly position of the absorption peak was determined by infrared(FTIR)and ultraviolet(UV),and the corresponding inclusion ratio was determined by nuclear magnetic titration.The inclusion complex of resveratrol with ?-cyclodextrin and its derivatives were studied by NMR 2D-ROESY experiment.The results showed that they could form stable inclusion complexes and the interaction of resveratrol with different hydrogen at different positions on the cyclodextrin;(2)we used the carboxymethyl-?-cyclodextrin reacted with oxalyl chloride and resveratrol in DMF to synthesize cyclodextrin-resveratrol(CDRes)covalent molecules with different degrees of substitution,the covalents are also characterizatized by infrared(FTIR)and ultraviolet(UV);Second,this part mainly researched inclusion complex of resveratrol and cyclodextrin on the molecular simulation.In order to simulate the microscopic behavior of molecular motion,we used molecular simulation theory and computer computing technology to enable the inclusion complex to exhibit the state of the molecule at the atomic level.Molecular docking is the method to study the interaction between host and guest molecules.In this paper,molecular docking software AutoDock 4.2 was used to study the molecular docking of resveratrol with dofferent type of ?-cyclodextrin.The rationality of the structure of the inclusion complex was theoretically verified,the minimum energy conformation was calculated and the chemical rationality of the inclusion complex structure was explained.Third,this part mainly introduced the stability of resveratrol monomer,cyclodextrin-resveratrol inclusion complex and formation of covalents between resveratrol and cyclodextrin.(1)Under the ultraviolet light irradiation of 365 nm,the change of the percentage of absorbance decay of these substances at a prescribed wavelength at different times was examined to explain the change in photostability.The results of light stability experiments indicated that the photo-stability of the formed covalents was higher than that inclusion complexes and the monomer,which requires the resveratrol derivative to be protected from light during the preparation process.(2)The stability of inclusion complexes,covalents and monomers at different pH was investigated.The experimental results showed that the degradation rate of resveratrol gradually increases with the increase of pH.Fourth,the preliminary studied on the anti-fatigue of cyclodextrin-resveratrol covalent derivatives was introduced.In this experiment,ICR(Kunming)mice were used as the research object and the detection model of exhaustion of mice was used as a model.In a suitable dose study,mice were gavaged for 30 days for a one-time exhaustive swim.By analyzing the weight of mice,exhaustive swimming time,blood lactate,liver/muscle glycogen,blood glucose,urea nitrogen,aspartate aminotransferase,glutamate aminotransferase,uric acid,et al.,to determine whether the newly formed derivative has a well anti-fatigue effect.The experimental results indicated that under the same conditions,the newly formed covalent derivatives have well anti-fatigue effects.