Study On The Interaction And Properties Of Coumarin Compounds And Citrullus Ring

Cucurbiturils are a class of supramolecular compound with a larger hydrophobic cavity and polarity carbonyl modified port,which can form stable host-guest complexes with object molecular by the cage body,hydrogen bond and van der Waals force,etc.The are also non-toxic,extensive host-guest recognition and promising pharmaceutical carrier.The coumarins have anti-cancer,anti-inflammatory,anti-oxidation and other physiological activities,but its poor water solubility and low bioavailability limits its further clinical application.In this paper,cucurbit[7]uril?Q[7]?and cucurbit[8]uril?Q[8]?were selected as the hosts,and 7-Hydroxycoumarin?UBF?,Daphnetin?DPN?,Coumarin-3-carboxylicacid?C-3-CA?,Scoparone?SPO?,3-Aminocoumarin?3-AC?,Psoralen?PSA?and Angelicin?AGC?were selected as the guest molecules.To study the host-guest function of coumarins-cucurbiturils,and to investigate the cucurbiturils influence on the stability,water solubility,antioxidant activity and in vitro release pathway of coumarins provided a theoretical basis for the utilization of coumarins.?:UV-Vis spectroscopy was used to investigate the interactions of the7-Hydroxycoumarin,Daphnetin,Coumarin-3-carboxylicacid,Scoparone,3-Aminocoumarin,Psoralen and Angelicin with Q[7]and Q[8].The results showed that 7-Hydroxycoumarin,Daphnetin,Coumarin-3-carboxylic acid,Scoparone,Psoralen and Angelicin had no interaction with Q[7].Q[7]formed a 1:1 inclusion complex with 3-Aminocoumarin,and the binding constant by UV absorption was3.789×10⁴ L·mol^-1.Q[8]formed a 1:1 inclusion complex with 3-Aminocoumarin,Psoralen and Angelicin,and the binding constants by UV absorption were 2.551?10⁵L·mol^-1?7.4395?10⁶ L·mol^-1 and 6.3598?10⁶ L·mol^-1,respectively.Fluorescence spectroscopy,infrared spectroscopy and isothermal titration calorimetry further confirmed the interaction of 3-Aminocoumarin with Q[7]and 3-Aminocoumarin,Psoralen and Angelicin with Q[8].The ¹H NMR spectroscopy showed that the mode of action was that 3-aminocoumarin completely entered the internal cavity of Q[7]and Q[8];Psoralen and Angelicin also completely entered the internal space of Q[8].In addition,we investigated the inclusion effects of Q[7]and Q[8]with 3-AC at different pH values,and the inclusion effects of Q[8]with PSA and AGC at different pH values.The results showed that Q[7]and 3-AC formed a host-guest complex with a molar ratio of 1:1 only at pH=1.03,Q[8]formed a 1:1 inclusion complex with 3-AC or PSA at pH less than 7,AGC could form a molar ratio of 1:1 host-guest complex with Q[8]at pH=2.05⁶.97.?:The effects of Q[7]and Q[8]on the water solubility,stability,antioxidant activity and cumulative release of 3-AC were studied by ultraviolet absorption spectroscopy;and the influences of Q[8]on the water solubility,stability and cumulative release of PSA and AGC were investigated,too.The results showed that the intervention of Q[7]and Q[8]increased the solubility of 3-AC in aqueous solution by 1.26 times and 2.04 times,respectively;Q[7]had no effect on the stability of 3-AC;The IC₅₀ values of 3-AC and?3-AC?-Q[7]inclusion complex for removing ABTS radicals were 1.06×10^-5 mol·L^-1 and 1.41×10^-5 mol·L^-1,respectively.Q[7]decreased the cumulative release of 3-AC in artificial gastric juice and intestinal juice,but made3-AC have a certain sustained-release effect in artificial gastric juice.Q[8]had little effect on the antioxidant activity of 3-AC,3-AC and?3-AC?-Q[8]inclusion complex for removing ABTS radicals were 1.06×10^-5 mol/L and 1.41×10^-5 mol·L^-1,respectively.but reduced the stability and cumulative release of 3-AC in artificial intestinal fluid.Q[8]increased the solubility of PSA and AGC in aqueous solution by1.71 times and 1.6 times,and did not affect the stability of PSA and AGC in artificial gastric juice and intestinal juice.At the same time,Q[8]intervention decreased the cumulative release of PSA in artificial gastric juice and intestinal juice.Q[8]increased the cumulative release of AGC in artificial intestinal juice by 1.2 times,but in artificial gastric juice,the cumulative release rates of AGC and AGC-Q[8]inclusion complex were 53.57%and 40.84%respectively after 720 minutes.The cumulative release rate of AGC-Q[8]inclusion complex was slower than that of AGC,indicating that AGC-Q[8]inclusion complex is more stable in artificial gastric juice than in artificial intestinal juice.