Constructions Of Artificial Transmembrane Ion Transporting Systems And Their Properties

Biological membranes and ion transport systems exist in almost every living organism. Life requires particularly sealed environment, but also need to communicate and exchange matters constantly with outside world. The transport is of high efficiency and selectivity, the process is tunable by the organism and will in turn influence the state of the organism. Thus, the activity and molecular basis of transmembrane transport of ions, water and carbohydrate is critical to lives. With the presence of a system like this, organisms are able to perform regular metabolism and other physiology activities, like heartbeat, taste, touch and nerve impulse.It has been 34 years since the first reported synthetic ion channels in 1982. Chemists have been constantly trying to construct ion transporting systems that can compete with the natural ones. From the modified cyclodextrine in the beginning to recently reported foldmers, from the polypeptides to inorganic carbon nanotube, from the single-carbon gaseous fluorinated simple molecules to complicated DNA nanomachines, various building motifs were used to construct artificial transmembrane transport system. The endeavor is not only attributed to the key importance of mass transmembrane transporting systems, but also because scientists want to learn from one of the most delicate and efficient system in nature and try to understand the theory and rules behind.Thanks to the fast development of science, different characterization methods are available now, enabling us to investigate both the artificial and natural ion transporting systems in details. More and more artificial systems have showed excellent performance in vitro and in vivo, building a good foundation for the future development of therapy for channelpathies, drug delivery system, and clinical tools. Besides, natural channels modified by genetic engineering and chemical methods have already been applied to area like DNA sequencing and water purification with some products marketed.But the development of artificial transmembrane system still faces big challenges together with many opportunities. First of all, most of the current artificial systems lack the high efficiency and selectivity found in natural channels. For application out of the lab, a high efficiency and a minimum dosage is an important factor. Secondly, the construction of “living” artificial ion channels, that is the intelligent transmembrane systems, is still in its infancy. The creation of intelligent systems by learning from the nature is an ultimate goal for chemical science.Therefore, based on the simple and accessible chemical synthetic method, we constructed three ion transporting systems through rational design. Within these systems, we tried to investigate on the issues of high efficiency in ion transport, the smart and generally applicable system, and good ion selectivity.1. Based on the well-studied tripodal ion transporters, we use simple molecules containing different chalcogen atoms as scaffolds and the thioureas as hydrogen bonding donors for binding anions to build highly efficient bipodal anion transporters. We characterized the chloride binding constants, lipophilic properties and ion transporting efficiencies of the 9 new transporters in detail, and tried to analyze the relationship between these elements. We found different chalcogen atoms and aromatic substituent groups have clear impact on the overall efficiency of the transporters. And among these new transporters, the one with highest activity can almost reach the behavior of the natural compounds.2. Later on, by using the selenium containing bipodal anion transporters, we have constructed smart nanoparticle systems. The system can respond to biology related thiol groups(like GSH and Cys). At the nanoparticle state, the transporting activity is totally closed because of aggregation effect. The nanoparticles can be dispersed in water at high concentration due to the small size, making the system available in aqueous environment. When activated by thiols, the system can be regulated quantitatively in different methods because of the high sensibility of the system. We can detect Cys molecules with the system at a nanomolar concentration.3. Finally, a transmembrane channel system was built with nanometer-sized artificial helices of well-defined structures. As a combined effect of the rigid scaffold, suitable size that matching the lipid bilayer and the multiple lipophilic side chains, the channel system possess particular stability and ion transporting efficiency. Through further comparing the ion selectivity, single-channel lifetime and conductance property, it was found the system can also be used as accessible models and tools for studying natural protein channels.These novel ion transporting systems have distinct characters. These new systems are very promising in applications and may perform desirable biological functions in suitable situations.