Preparation And Characterization Of Supramolecular Micelles And Artificial Transmembrane Channels Based On Functionalized Acyclic Cucurbituril

Supramolecular chemistry is a discipline focused on molecular recognition and self-assembly,which has extensive applications in the fields of drug delivery and artificial ion transmembrane channels.Currently,numerous macromolecules with novel structures and diverse functions have been reported in an endless stream,which have a certain impetus for the development of supramolecular chemistry.Among them,acyclic cucurbituril（ACB）has been widely studied due to its unique C-type flexible cavity and good water solubility.In order to further explore the application of ACB in drug delivery and artificial transmembrane channels,in the first part of this thesis,a dual responsive supramolecular micelle was prepared by functionalized acyclic cucurbituril and the derivative of camptothecin for targeted cancer treatment,which may provide some ideas for the research of intelligent drug delivery system.In the second part,a series of artificial unimolecular transmembrane channel molecules were synthesized based on crown ether and ACB.We then verified their ability inserting into the membrane and selective transport ability for alkali metal cations.The main research contents are as follows:1.Folate modified acyclic cucurbituril（ACBFA）was synthesized,and a prodrug（Adss CPT）was formed by the anticancer drug camptothecin modified with adamantane bonded with disulfide bonds.The amphiphilic complexes between ACBFA and Adss CPT was formed through host-guest interactions,which can form supramolecular micelles self-assembly.Firstly,its structure were demonstrated by NMR,XRD and FT-IR,and it was proved that functionalized acyclic cucurbituril and camptothecin derivatives formed a complex with a stoichiometric ratio of 1:1 and its binding constant（Ks）reaches to 5.78×10⁴ M^-1 through fluorescence experiments.Secondly,it demonstrated that supramolecular micelles were characterized by TEM and it has a dual response effect under acid and glutathione condition in vitro release experiments.Finally,through MTT experiments,it was proved that the cytotoxicity of supramolecular micelles on three human cancer cell lines（Hep G2,A549,Hela）was stronger than normal cells（LO2）and better selectivity.Laser confocal microscopy showed that it had specific targeting properties for cancer cells.The strategy has certain reference value for clinical cancer treatment to construct supramolecular drug delivery system based on targeted acyclic cucurbituril.2.A series of unimolecular transmembrane channels are synthesized based on acyclic cucurbituril and crown ethers.First,three acyclic cucurbiturils with different chain lengths are modified and then linked with crown ether to obtain a series of transmembrane channel molecules.The artificial channel molecules were successfully prepared verified by ¹H NMR and HR-MS.The fluorescent experiment of vesicles encapsulating fluorescent molecules demonstrated the ability of the transmembrane channel molecules,which inserting into the membrane and transporting alkali metal ions across the membrane.The results show that the artificial transmembrane channel molecules can insert into the cell membrane and have good selectivity for sodium ions.The chain length of artificial transmembrane channel molecules has an impact on the activity of ion transport,which provides a certain reference value for the construction of artificial transmembrane channel molecules.