Design And Synthesis Of Novel Biomimetic Transmembrane Channels Based On Helical Topology

In view of the excellent properties of natural ion channels and their significance for vital activities,it is important for us to study the structures and mechanism of ion transmission.As an alternate to natural ion channels,artificial ion channels are not only a simplified model of natural channel proteins,but also can overcome the structural defects of proteins.Artificial ion channels are promising for the potential application in the fields of energy,medicin and water purification.The chemical diversity of channel structures also brings some difficults for the design of artificial ion channels.It is extremely difficult for synthetic compounds to form stable ion pathways across the long hydrophobic lipid bilayers,but the helical topology may cross this barrier.A spring-like helix is cinstructed via the folding of a liner chain,which is much less difficult to prepare than the direct synthesis of nanotubes.Therefore,the development of ion transport system based on helical topology is important for the development of artificial ion channels.We sought to develop a new type of helical artificial ion channel based on the reliable molecular design and the application of various synthetic methods.Herein,we respectively prepared three different artificial helical ion channels by using supramolecular chemistry,covalent chemistry and dynamic covalent chemistry methods.We hope to utilize different synthetic approaches to develope the method of constructing helical topology of ion channels,and discuss the structure-property relationship under one channel framework.1.Helical supramolecular polymer channelsThe "magic" function of natural ion channels is derived from their sophisticated protein structures.The imitation of natural ion channel is an important research topic for artificial ion channels.Supramolecular polymers may offer a promising solution to the nearly impossible task of synthesizing the intricate structure of proteins.However,the development of supramolecular polymers in topological structure is still slow.Herein,we present a simple strategy to control the topology of supramolecular polymers by using a shape persistent building block.According to this method,we successfully prepared helically folded supramolecular polymers,which can spontaneously fold into a helical nanotube containing a cavity.This is the first predictable molecular self-assembly system in which the resulting supramolecular polymers can fold into helical conformation by design.We found that such big channel can span the membrane to facilitate the transport of glucose.2.Positive charged helical polymer channelsIn natural ion channels,the mutation of amino acids seuqence at particular sites will seriously affect the channel properties.The study of structure-properties relationship is very important for understanding the transport process of ions in channels.As a simplified model,artificial pore structures provide great opportunity to uncover the structure-function relationships of ion channels.Although several examples have recently been reported to functionalize the channel,the modification positions of channels,mainly concentrating on the edges or inner macrocycle skeleton,look like typically planar barrier.Actually,the diversity of pore structures is seriously limited,due to the fact that it is difficult to make arbitrary chemical modifications inside the nanochannel.To realize this idea,a suitable molecular scaffold is necessary.Recently,we have reported a new series of molecular channels based on conjugated helical polymers.Herein,we demonstrated the helical polymer scaffolds potential to carry out predictable chemical modification inside the channel structures,and consequently reported a novel type of positively charged channels based on helical polymer scaffold in which the quaternary ammonium charged groups were regularly installed on the inner surface of channel structure.We found that the modified helical channels exhibited the expected ion transport properties.Due to electrostatic repulsion between positive charges,the original cation channel was converted into anion channel,and acted as a size-selective anion channel.3.Dynamic covalent helical oligomer channlesWe have developed two types of artificial channels that were prepared via either covalent helical structures or noncovalent helical ones,but the tedious synthesis procedure seriously limit the development of this field.Inspired by nature,we present a highly efficient method for the preparation of helical ion channels,that is,utilizing the dynamic covalent chemical strategy to directly prepare helical polymer ion channels.Such dynamic covalent oligomer channels can spontaneously fold into helical nanotubes under the steric hindrance effect.The dynamic covalent helix channels can accelerate the movement of ions across the lipid membrane and exhibt structure-arisen transport features.