Design,Synthesis And Application Of Intelligent Aromatic Helical Structure Modulated By Metal Ion

Helical structure is one of the most basic structural units in living system,which bears various unique functions in the life activities.For instance,the double helix of DNA can skillfully realize the storage and transfer of genetic information,while the alpha helices of proteins are closely related to the selective transmission of material between inside and outside the cell membrane,enzyme catalysis and the special recognition for antibodies.In order to mimic the structure and function of natural helix,scientists have designed artificial helical structures by using synthetic system and developed few new applications of them.Owing to the stable structures and predictable folded conformations,aromatic helices have been rapidly developed in the last two decades.At the same time,the potential dynamic characteristics of aromatic helices,such as the conformational conversions involving extension-compression,folding-unfolding,as well as single and double helices,provide the broad application prospect in the field of intelligent materials.In addition,the inherent handedness and special cavities of aromatic helical structures allow scientists to develop their potential applications such as ion channels,specific recognition,controllable encapsulation and release of guest molecules,and chiral separation by properly designing the sizes and microenvironments of their inner cavities.Recently,many types of aromatic helices have been designed and synthesized based on increasingly mature design concepts and diverse structural fragments and weak interactions.However,due to the limitation of low reactivity and poor solubility caused by the overly rigid structure of aromatic helix,the functional design and synthesis of aromatic helix are still facing great challenges.It is particularly noteworthy that the inner cavities in the most of the aromatic helical structures reported so far are too small and unadjustable as a result of their compact conformations.Few exceptions only focused on the design and optimization of structures,which greatly restrict the development of their intelligent functions.Herein,two types of aromatic helices including hollow helix with open cavity and helical capsule with closed cavity were designed and synthesized in this paper,and their conformations were reversibly regulated by complexation and decomplexation of metal ions,so as to explore their potential applications in gated ion channels and controllable encapsulation and release for guest molecules.1.Design and synthesis of intelligent aromatic helical structure which can undergo the interconversion between single-and double-stranded helices regulated by metal ionBy using 1,10-phenanthroline derivative as the building block as well as a simple and efficient Click reaction in which the synthesis strategy of first complexation and then decomplexation overcome the restriction of reactivity from the steric hindrance of the reaction site,a new type of hollow aromatic helical trimers with different side chains was successfully obtained.Then,the stable hollow helical conformation of the target molecule in solid phase and solution phase was proved by 1H NMR and 2D NMR,CD spectra and X-ray single crystal diffraction.Based on the multi-nitrogen atoms in the cavity of the target helical molecule,the intertwined double helical structure formed via the coordination of helical trimmers and Cu ions was also confirmed by X-ray single crystal diffraction.Subsequently,the reversible interconversion between hollow single helix and double helix was further confirmed by the 1H NMR,UV-Vis,fluorescence and CD titration experiments.2.Construction of gated ion channel by means of self-assembled one-dimensional（1D）hollow helical tubeAlthough the synthesis of aromatic helices with large molecular weight is very difficult,the aromatic helical oligomers can produce a hollow helical tubular structure in 1D direction through the full overlap head and tail of them based on the π-π interactions.By using AFM,SEM and TEM,the hollow helical tube formed by single helix of the target trimer was proved,and this structure can be reversibly assembled and reassembled via the complexation-decomplexation of Cu ions.At the same time,the transmembrane ability of 1D hollow helical tube was confirmed by fluorescence microscope.Subsequently,large unilamellar vesicles（LUVs）encapsulated with 8-hydroxypyrene-1,3,6-trisulfonate（HPTS）were used to evaluate the ion transport activity of 1D hollow helical tube.The results showed it possesses stable and effective ion transport activity.Finally,with the addition of Cu ions into 1? LUVs and aqua ammonia into1₂-[Cu（CH₃CN）₄PF₆]₄,the activity of ion channels in situ inside lipid bilayers were gradually turned off and turned on,respectively.Therefore,by using the 1D hollow helical tube formed by the target trimer helix which can generate reversible assembly and disassembly based on the interconversion between single and double helices triggered by Cu⁺ and NH₃·H₂O,the first reversible ligand-gated ion channel in situ inside lipid bilayers was successfully constructed.3.Design and synthesis of intelligent aromatic helical capsules which can undergo the partial unfolding regulated by metal ionBased on the approximate angle of 60° between the position of 2 and 9 in 1,10-phenanthroline and its special coordination geometry with Cu⁺/Cu²⁺,a type of helical capsule molecules with closed and fully heteroatomized cavity was designed and synthesized by using 1,10-phenanthroline as the centrally located structural unit,1,3,4-oxadiazole as the bonding mode,and quinoline dimer as the structural fragment of sealing end.The stable helical conformation of the target molecule in the solid and solution phases was proved by means of 2D NMR,CD spectra and X-ray single crystal diffraction.Subsequently,the selective coordination between the helical capsule and Cu²⁺ was initially identified by 1H NMR,UV-Vis,fluorescence and CD titration experiments,and the local conformation of the aromatic helical capsule was reversibly regulated by the addition of Cu²⁺ and NH₃·H₂O in sequence.