Hydraphiles

Figure 12.14 Schematic diagram of the hydraphile family of ion channel mimics.

Figure 12.15 Conformation adopted by the hydraphiles based on dizaz[18] crown-6 within a bilayer membrane such as phosphatidyl choline deduced from experimental evidence (circles represent alkali metal cations).

Another way to assess ion channel conductance is to use artificial phospholipid vesicles (liposomes) as cell models. These structures (described in more detail in the next chapter) are commonly used to transport vaccines, drugs, enzymes, or other substances to target cells or organs. The vesicles, which are several hundred nanometres in diameter, do not suffer from interference from residual natural ion channel peptides or ionophores, unlike purified natural cells. A liposome model was used to test the ion transport behaviour of the redox-active hydraphile 12.36. The compound transports Na+ and the process can also be monitored using 23Na NMR spectroscopy.26 The presence of the ferrocene-derived group in the central relay allows the ion transport to be redox-controlled - oxidation to ferrocinium completely prevents Na+ transport for electrostatic reasons. Some representative data from a planar bilayer measurement is shown for hydraphile 12.36 in Figure 12.16. 

There are two basic kinds of chemical models structural and functional. Functional models are harder to design and may not physically resemble the system they are designed to mimic (e.g. hydraphiles) but do make use of the same concepts. Was can also distinguish confirmatory and speculative models depending on whether the model is based on a known biological structure or not. 

Gokel, G. W., (2000) Hydraphiles design, synthesis, and analysis of a family of synthetic, cation-conducting channels Chem. Comm. 1-9. 

Fig. 5.15 Transmembrane channels formed by crown ethers a single filter chundle approach [45] (left) and multifilter hydraphile [46] (right)...

A fluorescent derivative was prepared and it was demonstrated by fluorescence microscopy that the hydraphiles insert in the phospholipid bilayers of the bacterium Escherichia coli <2002JA9022>. The channels are symmetrical and therefore nonrectifying. As such, they permit ions to pass readily in both directions through the organism s outer (plasma) membrane. This makes the hydraphiles toxic to bacteria because the channels permit internal and external ion asymmetry to be disrupted <20050BC1647, 2005OBC3544, 2005CC89>. 

An example of such a synthetic mimic is the hydraphile channel system developed by Gokel. The system is based on the 4,13-diaza-18-crown-6 macrocycle 3 (Fig. 2), with an inner crown ether believed to be embedded in the... 

Figure 21 Natural crown ethers and biomimetic crown ethers (a) nonactin (b) valinomycin (c) a barrel-stave model (d) a hydraphile. " ...

Figure 11 (a) Hydraphile model channel 21 and (b) cartoon representation of hydraphile mode of action. 

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