Supramolecular Aggregation And Transmembrane Transport Of Peptide-Based N-Amidothioureas

Helical structures are ubiquitous in nature,especially in biological systems,and the discovery of DNA double helix is of epoch-making significance.Recent years have witnessed the rapid development of supramolecular helix based on intermolecular noncovalent interactions that simulate natural helix in structure and function,which is of help in understanding the origin of life and in designing functional materials.As a research hotspot of supramolecular chemistry,transmembrane transport recently has attracted attention.In this context,artificial transporters have been employed to treat diseases caused by disorder of ion transport,which also exhibit potential in developing new anti-cancer treatment.In this dissertation,β-turn structured peptide-based N-thiothiourea was employed as structural motif of folded short peptides,aiming to construct novel supramolecular aggregates and ion channels for transmembrane transport.This dissertation comprises four chapters.In chapter 1,the concepts of the β-turn,N-amidothiourea and halogen bonding are firstly introduced.Subsequently,examples of supramolecular helix constructed from benzene-1,3,5-tricarboxamide(BTA),helical fragments,and halogen bonding are summarized.Finally,the strategies of designing ion channels based on helical peptides and self-assembled molecules in transmembrane transport are introduced,as well as the current research progress in macropore channels,adjustable transmembrane channels,and halogen bonding-mediated transport.In chapter 2,benzenetriamine-based trilateral alanine-based amidothioureas LLL/DDD-XA(X=H,F,Cl,Br,I)are designed and synthesized,which contain three β-turn structures.Absorption and CD spectra,SEM and DLS studies reveal that only iodinesubstituted molecules form supramolecular aggregates in acetonitrile,indicating the significant role of iodine substituents in the formation of supramolecular aggregates.The aggregation of the benzenetriamine-based trilateral thioureas(N-BTA)is significantly different from that of the previously studied benzene-1,3,5tricarboxamides(C=O-BTA)based counterparts,which is of help in understanding the supramolecular assemblies of BTAs and analogues.In chapter 3,the transmembrane transport of alanine-based bilateral Namidothioureas with naphthalene linker are investigated.Through fluorescence spectroscopy with labeled vesicles,patch clamp technology,and nuclear magnetism,it was confirmed that the N-amidothiourea molecules formed ion channel on the membrane.At high and low concentrations,the transport activity of the channel molecules is inconsistent.At very low concentrations,only the anion can be transported.At high concentrations,large pores which preferentially transport cations are formed,and also allowing small molecules transport.This proves that we have developed a novel concentration-dependent transport mechanism with adjustable functions.Also,channels formed by halogenated derivatives at high concentrations halogenated derivative-forming have strong molecular synergy,indicating that halogen bonding may existence driving the formation of channels.In chapter 4,we designed and synthesized folded short peptides LL-/DD-NPheX(X=H,F,Cl,Br,I)of bilateral phenylalanine aminothiourea with naphthalene as connecting arm,which successfully constructed supramolecular helical polymers in aqueous solution by the β-turn folding structure and multiple intermolecular forces.Also,we connect the self-assembly properties in the aqueous solution with the transmembrane transport properties on the lipid membrane.The supermolecular aggregation behavior changed with the different amino acid residues so that controlling the distribution ratio of molecules in the membrane or solution and studying the formation process of ion channels.This result is of great significance for the design and regulation of self-assembled ion channels.