Channel-Forming Systems

Successful synthetic transmembrane channels must have three characteristics if they are to replicate the behaviour of natural systems. They must span the cell membrane, implying a single molecule or stable self-assembled complex over 4 nm in length. Ideally they should also be able to discriminate in favour of one chemical species, if they are to mimic the highly selective channels, and transport that species at rates in the region of 104 to 108 ions per second to match the efficacy of natural channels. 

Several channel architectures have been considered when designing artificial mimics. The most obvious biologically inspired method is to prepare extended helical molecules in an attempt to reproduce the channels either within the helix or where the molecules meet. A small number of systems have been designed using this 

The first attempts to prepare artificial ion channels came as a result of work on [18]crown-6 derivatives, examples of which are shown in Fig. 5.15. The Lehn group s crystal structure of the potassium salt of their tetracarboamido[18]crown-6 showed that the macrocycles formed an extended one-dimensional stack with 

Crown ethers are attractive platforms from which membrane-spanning substituents can be appended but suffer from a lack of rigidity. It can be argued that cyclic compounds with well-defined central cavities should be more robust and selective. The cyclodextrins and calixarenes have both been employed in ion channel mimetic compounds. These compounds can have different functional groups at their 

Calixarenes, in particular calix[4]arene, have been seen as potential ion selective filters around which ionophore or channel frameworks can be constructed. Calix[4]arenes exist in different conformers, two of which are of interest as platforms for transmembrane ion transport the cone conformer, in which all four 

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Channel electron multipliers, 24 105-106 Channel-forming systems, crown ethers in, 24 59... 

Channel-forming toxins and antibiotics. Some of the bacterial toxins known as colicins (Box 8-D) kill susceptible bacteria by creating pores that allow K+ to leak out of the cells. One part of the complement system of blood (Chapter 31) uses specific proteins to literally punch holes in foreign cell membranes. Mel-litin, a 26-residue peptide of bee venom,372 373 as well as other hemolytic toxins and antibiotic peptides of insects, amphibians, and mammals (Chapter 31) form amphip-athic helices which associate to form voltage-dependent anion-selective channels in membranes.374-377... 

The simulation of ion channels and other pore-forming peptides and proteins at atomic detail is nowadays also possible. With the increase in computational power, these complex systems have attracted much more interest, and several simulations have been reported. Very often, only the transmembrane segments of the channel-forming proteins are included in the simulation to reduce the size and complexity of the system. The simulated systems range from synthetic model ion channels to a bacterial porine protein. 

Fig. 2.8 Components of a karstic system sinkholes and fissures acting as inlets for rapid intake of runoff water dissolution channels water discharging in springs at local bases of drainage, for example, river beds caves exposed at former dissolution channels formed at former (higher) drainage bases.

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