| In biological systems, the transport in and out of cells for the most of polar solutes is highly regulated by the channel proteins. The disorder of the channel proteins might lead to some channelopathies. Currently, the transport mechanism of the most solutes has not been uncovered yet. Chemist proposed to build artificial systems to mimic the structure and function of the channel proteins. In the last three decades, considerable effort has been devoted to the construction of artificial ion channels on the basis of the supramolecular strategy and thus the selective transmembrane transport of Na+, K+, Ca2+ and Cl- has been achieved. However, the selective transport of H+ and the controllable transport of ions are still to be challenge. In this dissertation, we established a new strategy to build artificial transmembrane channels. We proposed to build artificial channels by combining the covalent synthesis and non-covalent assembly method. The single-molecular channels that have the length similar to the thickness of the lipid bilayer have been designed and synthesized with pillar[5]arene backbone. The selective transmembrane transport of H+ and voltage-gated transmembrane transport of K+ have been achieved.In the first part, two kinds of new organic tubular assemblies have been constructed from pillar[5]arene and its derivatives. Pillar[5]arene gelates organic solvents through the formation of tubular fibers which are evidenced by TEM and XRD experiments. Pillar[5]arene with deca-ester has been further prepared. This deca-ester derivative assembles into two different channels under the template effect of water wires, which is supported by single-crystal analysis. In addition, IR experiments demonstrate that the water wires in the nanotubes can be under selective proton conductance.In the second part, artificial transmembrane proton channels have been constructed. Water wires docking inside the natural proton channels provide one of the important pathways for proton transport across cell membranes. In this part of work, we describe the first example of water-wire-based artificial transmembrane channels constructed from pillar[5]arene monomeric and dimeric derivatives. The single-channel conductance measurements and the isotope effect experiments in acidic conditions support that the new artificial channels possess high capability and selectivity for proton transport which is mediated by water wire formed in the tubes of the pillar[5]arene backbones. The dimeric structures with the hexamethylene linker exhibit the highest channel activities due to the maximized stacking of their pillar[5]arene units, and the channel activity can be modulated by sodium ion and alkane-α,ω-diols.In the third part, the single-molecular tubular artificial channels have been constructed. A series of pillar[5]arene derivatives have been synthesized by attaching the peptides with different amino acid residues and length. The derivatives self-assembled to form tubular structures driven by the intramolecular hydrogen bonding, which is supported by the 1H NMR and IR experiments. The fluorescence experiments further reveal that the tubular structure can mediate the Cl- transport and the Phenylalanine tripeptide attached tubular structure show the highest transport activity.In the forth part, the voltage-gated K+ channels have been constructed. Three new artificial transmembrane channel molecules have been designed and synthesized by attaching positively charged Arg-incorporated tripeptide chains to pillar[5]arene. Fluorescent and patch-clamp experiments revealed that voltage could drive the molecules to insert into and leave from lipid bilayer and thus switch on and off the transport of K+. One of the molecules was found to display antimicrobial activity toward Bacillus subtilis with half maximal inhibitory concentration (IC50) of 10μM which is comparable to that of natural channel-forming peptide alamethicin. |
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