초분자체를 이용한 인공 이온 채널의 형성 및 특성에 대한 연구

Abstract

This thesis describes the synthesis and characterization of artificial ion channels using metal-organic polyhedra (MOP) and amphiphilic alkylated guanidinium complexes. Construction of artificial ion channels from alkylated metal-organic polyhedra (MOP-18), demonstration of anion selective channels using positively charged metal-organic cages or barrels, and synthesis of an amphiphilic guanidinium complex as a nitrate selective transporter are presented. In Chapter 2, the first synthetic ion chann=el based on metal-organic polyhedra is described. The MOP used in this study, MOP-18, has a rigid framework with a large hydrophilic cavity accessible through two different types of windows, and lipophilic tails. The ion transport activity of MOP-18 in lipid bilayers was investigated by both fluorometry and voltage-clamp method. Homogeneous, long-lived single channel currents were observed in planar lipid bilayer experiments. The MOP-18 channel preferred cations over anions, and the cation selectivity in the order of Li+ >> Na+ > K+ > Rb+ > Cs+. The observed cation selectivity suggests that the cation-？？？ninteraction between cations and the aromatic rings lining the windows of MOP-18 plays a crucial role in the ion transport. Compared with traditional organic synthetic ion channels, the ion channels made of MOPs have several advantages including easy synthesis, rigid framework, and tunability of the size and chemical environment of pores. Thus this novel ion channel system is not only useful as an artificial ion channel, but also may find other applications such as in sensor and catalysis. Anion transporters play an important role in the control of immunological responses, pH, cell migration, cell proliferation, and maintenance of membrane potential. Despite the importance of mimicking the natural anion transporters, however, most synthetic channels are cation selective. In chapter 3, the use of cationic metal-organic cages and barrels as anion selective ion channels is described. In this study, cuboctahderon metal-organic cages from the Fujita group, a cuboctahderon metal-organic cage from the Stang group, and a metal-organic barrel made of porphyrin and Pt2+ from the Mukherjee group were used. They all have +24 charges and large pores, which prompted us to explore their anion selective ion transport behavior because these positively charged metal-organic cages may attract anions toward their pores by charge-charge interaction. In planar lipid bilayer experiments revealed that all the cationic cages have an anion/cation permeability ratio larger than 1, which indicates they prefer transporting anions rather than cations. The Fujita…s cuboctahedron cages have a similar structure to MOP-18, but unlike MOP-18, they showed a small anion preference. Most interestingly, the metal-organic barrel from the Mukherjee group showed the largest anion preference (Cl-/K+ = 5.2 ) among them. It has an anion selectivity in the order of Cl-> Br- > I- > F- and also transports large molecules such as carboxyfluorescein. This ion channel system may thus be used for the treatment of diseases caused by misregulation of chloride transporter. Futhermore, this study shows the possibility to design ion channels with desirable properties by judicious choice of metal ions and ligands.Chapter 4 describes a nitrate ion selective transporter from amphiphilic alkylated guanidinium compound. Our group has reported the synthesis of 3,4,5-tridecyloxy-1-phenylguanidine (1), which self-assemble into a columnar structure in the presence of anions (NO3-, BF4-, Cl-). The long alkyl chains located at the outer rim may be able to incorporate this compound into lipid bilayers to act as an artificial ion channel. Proton transport experiments and concentration dependent ion transport experiments demonstrated that this amphiphilic guanidinium can act as an ion channel. Interestingly, the guanidinium and nitrate compex (1+NO3-) transported nitrate ion selectively over chloride and sulfate. This selectivity suggests that ion transportation took place by ion hopping through the columnar center because only the nitrate complex can form a columnar structure. Since nitrate is an environmentally important anion for plants and animals, this system may find useful applications such as in therapy and sensor.