Synthetic ionophores

A second source of inspiration for studying the open-chained equivalents of crown ethers was the observation that a number of naturally occurring antibiotics enhance cation transport and bear a structural similarity to open-chained crown ethers. A number of groups have examined neutral synthetic ionophores and a variety of novel cation carriers is now available. This is discussed in Sect. 7.4, below. 

Hilgenfeld, R., Saenger, W. Structural Chemistry of Natural and Synthetic Ionophores and their Complexes with Cations, in Topics in Current Chemistry (ed. Boschke, F. L.), p. 8, Berlin—Heidelberg—New York, Springer 1982... 

Active Transport of Ions Using Synthetic Ionophores... 

Table i. Active and selective transport of sodium, potassium and cesium ions with synthetic ionophores ... 

Table 4. Amounts of cation transported by the synthetic ionophores through chloroform liquid membrane after 2 days...

Anyway, it is clear that the fmdings obtained in these artificial transport systems do contribute to the understanding of biological phenomena and point the way to possible practical applications, such as the separation of ions. Accordingly, the development of synthetic ionophores which possess high selectivity for specific cations is expected to gain importance in the future. 

In this review, recent development of active transport of ions accross the liquid membranes using the synthetic ionophores such as crown ethers and other acyclic ligands, which selectively complex with cations based on the ion-dipole interaction, was surveyed,... 

Okahara, M., and Nakatsuji, Y. Active Transport of Ions Using Synthetic Ionophores Derived from Cyclic and Noncyclic Polyoxyethylene Compounds. 128, 37-59 (1985). 

Active Transport of Ions Using Synthetic Ionophores Derived from Macrocyclic Polyethers and the Related Compounds... 

Structural chemistry of natural and synthetic ionophores and their complexes with cations. R. Hil-genfeld and W. Saenger, Top. Curr. Chem., 1982,101,1-82 (346). 

Active transport of ions using synthetic ionophores derived from macrocyclic polyethers and related compounds. M. Okahara and Y. Nakatsuji, Top. Curr. Chem., 1985,128,37 (77). 

Some synthetic ionophores form complexes with metallic ions containing a varying number of ligands per metal ion, usually 1 or 2. It then holds for the overall concentration of ion J in the membrane that... 

The search for medicinal applications of crown ethers and cryptands has so far led to only a few pre-clinical studies. Many of the crown ethers and natural ionophores are toxic. Presumably the toxicity arises from the slow leakage of potassium out of cells and of sodium into cells. Antibacterial activity has been noted for several crown ethers and found to parallel potassium transport276). The established coccidiostatic activity of ionophores has led to the screening of crown ethers for coccidiostatic activity277). As yet the synthetic ionophores have shown no evidence of superiority over their natural product counterparts. 

Lariat ethers, which were designed to add dimensionality to the essentially flat crown ether, have been used as synthetic ionophores for decades. The binding properties of crown ethers are now well documented and generally well understood. Most such studies have been conducted with metal ions, although complexation of ammonium species and some neutral species (Gokel, 1973 Kyba, 1977) have also been reported. 

Crown ethers continue to be one of the most useful parts of supramolecular chemistry/91 From the beginning computations of metal ions complexes with synthetic ionophores/101 which have been aptly reviewed/111 emphasized the importance of including explicitly solvation in free energy calculations, also with ab initio calculations on calixarene complexes/121 Molecular dynamics simulations of 18-crown-6 ether complexes in aqueous solutions predict too low affinities, but at least correctly reproduce the sequence trend K+ > Rb+ > Cs+ > Na+. However, only the selection of K+ over Rb+ and Cs+ is ascribed to the cation size relative to that of the crown cavity, whereas K+ appears in these calculations to be selected over Na+ as consequence of the greater free energy penalty involved in displacing water molecules ftomNa/1131... 

Wipff, G., Troxler, L. (1994) MD Simulations on Synthetic Ionophores and on their Cation Complexes Comparison of Aqueous / non-Aqueous Solvents, in Wipff, G. (eds.), Computational Approaches in Supramolecular Chemistry, Kluwer, Dordrecht, pp 319-348. 

Vogtle has suggested that synthetic ionophores be classified as follows (21) cor-onands are macromonocyclic compounds with any heteroatoms cryptands are bi- and polymacrocyclic ligands with any heteroatoms and podands are acyclic coronand and cryptand analogs. The term crown ether is reserved for coronands with only oxygens as heteroatoms. Such a classification will be used hereafter. 

Bunzli, J.-C.G., 1987. Complexes with synthetic ionophores. In Gschneidner Jr., K.A., Eyring, L. (Eds.), Handbook on the Physics and Chemistry of Rare Earths, vol. 9. Elsevier Science Publ., Amsterdam, pp. 321-394 (chapter 60). 

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