Functionalized Supramolecular Self-Assemblies Based on Artificial Helix

Author:Zuo Teng Fei

Supervisor:liu jun qiu


Degree Year:2019





Helix is one of the most common structural conformations in living systems,which has endowed biological macromolecules with many unique characteristics.For example,DNA can finish the storage and transmission of one’s genes through the duplication,transcription and translation on the basis of its double-helix pairs.Inspired by nature,chemists are always trying to prepare artificial helical molecules by synthetic methods,in order to mimic the structure and function of natural helices.However,most of the research is focused on the property and function of single helix molecule,it still remains a challenge to construct supramolecular assemblies through the initial building block of artificial foldamers,and further to explore their special properties and functions.In this thesis,we have prepared three kind of helix-based functional supramolecular assemblies(i.e.supramolecular ion channels,pH-stimuli responsive“breathing”vesicles,and supramolecular nanocapsules with enantio-selective release abilities)on the basis of man-made aromatic oligoamide foldamers,whose helical conformation is driven by intramolecular hydrogen bond andπ-πinteraction.1.Supramolecular ion channels based on pyridine–pyridazine oligoamide foldamersAs the basic motif of living systems,there are always energy and materials exchange inside and outside of cell membranes.In this process,various channel proteins on the cell membrane undoubtedly play a crucial role.However,the natural channel proteins are difficult to extract and modify,which makes them more expensive than others.Therefore,how to construct artificial ion channels by synthetic methods has become one of the hottest research areas in recent years.In this chapter,a novel kind of pyridine–pyridazine based oligoamide foldamer was prepared,which can be used as a supramolecular ion channel,wherein alkali metal ions could be easily recognized and transported.This kind of artificial foldamer was directly acquired by the copolymerization of 4-isopropoxy-2,6-dicarboxylic pyridine and 3,6-diamine pyridazine in anhydrous DMF at room temperature,whose inner diameter and average length are 0.6 nm and 1.5 nm,respectively.The average length of pyridine-pyridazine based foldamer is shorter than the bilayer membrane thickness,while the artificial helix showed strongπ-πinteraction between individual aromatic foldamer,which made them easily to form a supramolecular nanotube in solution state,and further insert to the bilayer membrane due to its hydrophobic isopropyl side chains.In addition,owing to the nitrogen-rich cavities,this tubular assembly was enabled to serve as a supramolecular nanochannel,wherein alkali ions(i.e.Li~+,Na~+,K~+and Rb~+)could be easily recognized and transported.Circular dichroism spectroscopy,two-dimensional nuclear magnetic resonance,high resolution transmission electron microscopy and atomic force microscopy were utilized to verify the helical structure and supramolecular tubular assemblies of this pyridine-pyridazine based foldamer.The alkali metal ion recognition and transport performance were characterized by fluorescence spectroscopy and channel current of planar lipid bilayers.2.pH-stimuli responsive“breathing”vesicles prepared by foldable quinoline based artificial helixOne of the most interesting phenomena of natural elastin proteins(e.g.titin)is that they can fulfill some special functions by regulating the unfolding–refolding transformation of their microstructures.For example,muscle’s contraction and relaxation are closely related to the reversible unfolding–refolding structural transformation of elastin proteins.In recent years,the dramatic development of artificial foldamer makes it possible to mimic the unique unfolding–refolding transformation of titin at molecular level and further to fabricate high-level intelligent materials.Therefore,we prepared a novel quinoline-based aromatic oligoamide foldamer,which equipped with acid-stimuli responsive unfolding–refolding behaviors.When the nitrogen atom on quinoline units were protonated by acid,the helical structure of this foldamer was destroyed,resulting in an unfolding process.On the contrary,when the alkaline solution was added to neutralize the excess acid,the protonated nitrogen atoms on quinoline units underwent a deprotonation process,which promoted the structural transformation from the unfolded state to the initial folded state.We have prepared one kind of helix-based supramolecular vesicle which was self-assembled by the host–guest complex of azobenzene-linked foldamer andα-CD in aqueous solution.Interestingly,this vesicle performed periodic expansion and contraction movements in response to external pH stimuli,as we named breathing behavior.In this process,the wall thickness and membrane permeability of the supramolecular vesicles simultaneously changed.The membrane thickness variation of vesicles was clearly visualized from cryo-TEM instrument at frozen state.The pH-responsive permeability variation was characterized by fluorescence experiments,and MTT assay was also utilized to assess anticancer abilities of the drug-loaded vesicles.3.Supramolecular vesicles with enantio-selective release behaviors constructed by chiral aromatic foldamerBesides the ion-transportation and unfolding–refolding transformation behaviors,another widely investigated object of artificial foldamers is their chirality.Single handed foldamers could be easily acquired by appending a small chiral molecule(chiral inducer)to the C or N terminus of the artificial helices.Chiral induced helical oligomers have exhibited enantio-selective recognition and separation abilities according to previously reported literatures.In this work,we have prepared an M-helical oligoamide foldamer by attaching(1S)-camphanyl group to N terminus of the quinoline-based tetramer.Then an azobenzene group was linked to the artificial foldamer to recognizeα-CD,which further self-assembled into supramolecular vesicles in aqueous solution.We found this M-helix based supramolecular vesicle exhibited enantio-selective release behaviors toward racemic drugs.We employed propranolol(a frequently-usedβ-blocker)as a model drug to assess the enantio-selective release capabilities of this M-helix based vesicle.As a result,R-propranolol is preferentially permeated out from this supramolecular vesicle,and the M-helical oligomers on vesicular walls play a crucial role in this enantio-selective release process.