Construction Of An Oxidation-reduction Responsive Artificial Transmembrane Channels Based On Cyclodextrinpillararene Hybrid Molecules

Natural ion channels are pore-forming membrane proteins that mediate ion transport across cell membranes.They are essential for the regulation of the cellular environment,intercellular communication,and the conduction of biological signals.The transmembrane transport function of most channel proteins is precisely regulated by intracellular physiological signals such as membrane potential,p H,signal molecules,and mechanical forces etc.Under the stimulation of external signals,the conformation of channel proteins changes,to regulate the transmembrane transport process of channel proteins.After millions of years of evolution,channel proteins have precise structures and powerful functions,which have great potential to be applied in the fields of biomedical research and material chemistry.However,the poor structural stability of channel proteins and the easy inactivation of the two-layer environment away from phospholipids limit their application.The artificial transmembrane transport system based on the prototype of channel proteins with stable structure,high efficiency and advanced functions can not only provide a simple model for the study of the conformation of channel proteins,but also bring new ideas for the research of biomedical research,molecular sensing and other fields.In the past few decades,with the development of supramolecular chemistry,chemists have constructed a large number of artificial transmembrane transport systems with different struction and/or function.However,these studies mainly focus on the simulation of the basic substance function of channel proteins.There are few reports on the construction of artificial transmembrane transport systems with simulating-response function（such as gating）of channel proteins.It is expected that the novel artificial channel will have high transmission efficiency and oxidation-reduction responsiveness for transmembrane ion trabsportation.At the same time,we constructed artificial transmembrane channels with high selectivity,high transport efficiency and high antimicrobial activity by connecting brevis peptides on both sides of pillar[5]arene.The work of this paper mainly includes the following two parts:In the first part of this project,1,4-bis（2-propargyloxy）benzene and 1,4-bis（2-bromoethoxy）benzene were used as monomers to synthesize pillar[6]arene,functionalized with alkynyl and thioacetyl groups.The pillar[6]arene containing p-alkynyl group was covalently bonded with α-cyclodextrin（α-CD）containing mono-azido group by click reaction.Then,several sulfhydryl groups in the molecules were oxidized to form inter-macrocycle disulfide bonds to give tubular molecules with more rigid and stable structure.Since disulfide bonds are oxidation-reduction responsive,the conformation of these tubular molecules should be regulated by oxidation-reduction stimulators.The prepared target molecules have show very good membrane embedding ability and ion transport efficiency across the membrane.In the second part of this project,a new mono-molecule tubular channel was designed and synthesized by attaching bacitracin to the framework of pillararene.The terminal domains of the peptides are substituted by neutral,negatively or positively charged amino acid residues,respectively.The structureactivity relationship of the hybrid molecules with different charge statuses were studied,and their transmembrane transport properties and biological activities were evaluated.