Study On The Interaction And Properties Of Cucurbitacin And Antibiotic Compound

In this thesis,cucurbit[7]uril（Q[7]）and cucurbit[8]uril（Q[8]）were selected as the host,and thenchloramphenicol（CPE）,sulfonamides（HA）,sulfamethoxazole（SMZ）and trimethoprim（TMP）were selected as the guest to explore the host-guest interaction and the related properties of the inclusion complex after the interaction.The aim was to use a non-toxic and safe cucurbituril as a drug carrier to improve some defects of antibiotics,and combining the hemostatic effect of th cucurbit[8]uril to prepare coagulation antibacterial drugs.The interaction and mode of action of Q[7]and Q[8]with antibiotics were investigated by X-ray single crystal diffraction,UV-vis spectrophotometry（UV）,isothermal titration calorimetry（ITC）,fluorescence spectroscopy,Infrared Spectroscopy（IR）,nuclear magnetic resonance hydrogen spectroscopy（¹H NMR）and mass spectroscopy（MS）.The effects of Q[7]and Q[8]on the stability,solubility,in vitro cumulative release,antibacterial activity and coagulation of antibiotics were investigated by UV,constant temperature shaking method,agar slant culture method and four experiments of coagulation.The main research contents are as follows:1.The interaction between Q[7]/Q[8]and chloramphenicol and the effect of chloramphenicol properties.The interaction of CPE with Q[7]/Q[8]was investigated by X-ray single crystal diffractometer,UV,ITC,¹H NMR and IR.The results showed that both of them interacted with each other to form inclusion complexes with a binding ratio of 1:1,namely CPE@Q[7]and CPE@Q[8].The binding constant of CPE with Q[8]was 5.474×10⁵L/mol.¹H NMR analysis showed that CPE entered the Q[7]and Q[8]cavities,respectively.The single crystal structure of CPE@Q[8]showed that a Q[8]cavity encapsulates a CPE and a new supramolecular framework structure was constructed under hydrogen bonding force.The intervention of Q[7]and Q[8]had no significant effect on the stability of CPE,reduced its cumulative release rate in artificial gastrointestinal fluid,and slowed down the release time of CPE.The ability of Q[8]to inhibit Escherichia coli（E.coli）was 1.5 times that of CPE,and had little effect on the inhibition ability of Staphylococcus aureus（SA）.2.The interaction between Q[7]/Q[8]and trimethoprim and its effect on the properties of trimethoprim.The determination results of UV,fluorescence spectroscopy,MS,ITC,¹H NMR and IR showed that TMP interacted with Q[7]/Q[8]to form inclusion complexes TMP@Q[7]and TMP@Q[8]with a molar ratio of 1:1.The inclusion constant of TMP@Q[7]was 2.139×10⁴L/mol,with a mode of action in which the pyrimidine portion of the TMP molecular structure entered the Q[7]cavity;the inclusion constant of TMP@Q[8]was 1.711×10⁵L/mol,and the mode of action was that the entire TMP molecule entered the Q[8]cavity.The incorporation of Q[7]improved the solubility of TMP in aqueous solution by 7.75 times.There was no significant effect on the inhibition ability of SA.It increased the release rate of TMP in artificial gastric fluid,effectively prolonged the release time in the artificial intestinal fluid and had a certain sustained release effect.After the interaction of Q[8]and TMP,the stability and antibacterial activity were not affected,but it had a procoagulant effect,indicating that TMP@Q[8]had potential application value in coagulation and antibacterial.3.Study on the interaction of sulfonamide and sulfamethoxazole with cucurbit[8]uril,the construction of supramolecular framework structure and their properties.HA@Q[8]and SMZ@Q[8]crystals were cultured with ZnCl₂as crystal growth inducer.The crystal structures of HA@Q[8]and SMZ@Q[8]complexes were measured by X-ray single crystal diffractometer.The results showed that HA@Q[8]and SMZ@Q[8]formed two new supramolecular frameworks under the weak interaction force of non-covalent bonds.Among them,the HA@Q[8]supramolecular framework contained two forms of action:HA molecules entered the Q[8]cavity and interacted with the outer wall.The aniline group of SMZ entered the Q[8]cavity in the SMZ@Q[8]complex.The intervention of Q[8]had no significant effect on the solubility of HA and SMZ,reduced the cumulative release rate of HA and SMZ in artificial gastrointestinal fluid,and delayed the release time.Q[8]slightly improved the stability of SMZ in artificial gastric fluid,but had no significant effect on the stability of HA in artificial gastrointestinal fluid and SMZ in artificial intestinal fluid.