Ionophores metal cation transport

Applications.—Amino-acid anions have been shown to be transported across organic solvent membranes against their concentration gradient as counterions to metal-cation transport by macrocylic crown-type carriers. Optically active chiral crown ionophores have been used in liquid membrane electrodes for direct potentiometric determination of the enantiomeric excess in chiral ammonium... 

In mimicking this type of function, noncyclic artificial carboxylic ionophores having two terminal groups of hydroxyl and carboxylic acid moieties were synthesized and the selective transport of alkali metal cations were examined by Yamazaki et al. 9 10). Noncyclic polyethers take on a pseudo-cyclic structure when coordinating cations and so it is possible to achieve the desired selectivity for specific cations by adjusting the length of the polyether chain 2). However, they were not able to observe any relationship between the selectivity and the structure of the host molecules in an active transport system using ionophores 1-3 10). (Table 1)... 

By considering the stability constant and the lipophilicity of host molecules, Fyles et al. synthesized a series of carboxylic ionophores having a crown ether moiety and energetically developed the active transport of alkali metal cations 27-32). Ionophores 19-21 possess appropriate stability constants for K+ and show effective K+-selective transports (Fig. 5). Although all of the corresponding [15]crown-5 derivatives (22-24) selectively transport Na+, their transport rates are rather slow compared with... 

On the other hand, Bartsch et al. have studied cation transports using crown ether carboxylic acids, which are ascertained to be effective and selective extractants for alkali metal and alkaline earth metal cations 33-42>. In a proton-driven passive transport system (HC1) using a chloroform liquid membrane, ionophore 31 selectively transports Li+, whereas 32-36 and 37 are effective for selective transport of Na+ and K+, respectively, corresponding to the compatible sizes of the ring cavity and the cation. By increasing the lipophilicity from 33 to 36, the transport rate is gradually... 

A certain crown ether having additional coordination sites for a trasition metal cation (71) changes the transport property for alkali metal cations when it complexes with the transition metal cation 76) (Fig. 13). The fact that a carrier can be developed which has a reversible complexation property for a transition metal cation strongly suggests that this type of ionophore can be applied to the active transport system. 

Monensin belongs to the family of polyether ionophores. These compounds consist of a series of tetrahydrofuran and tetrahydro-pyran rings and have a carboxyl group that forms neutral salts with alkali metal cations. Their three-dimensional structure presents a lipophilic hydrocarbon exterior with the cation encircled in the oxygen-rich interior. They probably act by transporting cations through the lipid bi-layer of cell membranes, thereby preventing the concentration of potassium by the cells. Evidence for this is... 

Certain common features may be found in the complexation of alkali and alkaline earth metal cations by ionophorous agents and which aid in cation transport.8... 

The ion selectivities displayed by these antibiotics are lower than those of the neutral ionophores, and are given in Table 11. Many studies have been made on the properties of these ionophores, particularly with reference to the calcium-transporting abilities of A 23187 (146) and lasolocid (145). The search for new antibiotics is ongoing and there is constant addition to a list of about 50 distinct polyether antibiotics which have been isolated from various streptomycetes. Representative structures will be discussed here to illustrate the nature of complexation with alkali and alkaline earth metal cations. 

Examples such as this show the importance of alkali metal cation binding and transport in biochemistry, and a great deal of effort has been expended in supramolecular chemistry in attempts to understand natural cation binding and transport of the ionophore and channel type and to develop artificial systems capable of similar selectivities and reactivities. We will take a close look at many of these compounds in Chapter 3. 

Alkali metal transport in biochemistry is a vital process in maintenance of cell membrane potentials of use, for example, in nerve signal transduction and is at the core of some of the early work on artificial ionophores that mimic natural ion carriers such as valinomycin. Ionophore mediated ion transport is much slower than transport through cation and anion ion channel proteins, however. 

At physiological pH, the ionophores are ionized with the fat-soluble part of the molecule residing in the lipid bilayer of the membrane and the ionized moiety in the aqueous milieu (4). Binding of the metal ion takes place at the membrane surface As successive ether oxygen atoms from the ionophore bind to the metal, it loses its solvated water molecules, thereby forming a neutral zwitterionic metal-ionophore complex. Transport across the membrane can now take place, and at the opposite surface, the process is reversed to leave the metal cation and the anionic ionophore on the other side of the membrane. The... 

The anionic ionophores are highly selective for particular metal cations, and both kinetic and thermodynamic terms determine which cation is selected. Note that the thermodynamic stability of the metal-ionophore complex does not always determine the transport rate. For example, nigericin forms a much more stable complex with potassium but transports sodium much more quickly. In the presence of both sodium and potassium, however, the extra stability of the nigericin-potassium complex results in the preferential transport of potassium over sodium (4). 

The transport of alkali and alkaline earth metal cations by many crown ethers and their derivatives has been extensively studied. Much effort has been paid to increase their selectivity as well as their efficiency. Making highly Li selective ionophores is a primary concern in this field, because large quantities of lithium could be extracted from sea water for use to nuclear fusion generators... 

Electronic signals in nerve cells travel by means of metal-ion transport laterally in and out of the axon. Such transmembrane transport of ions is fundamental to cell biology, and attempts to mimic it artificially laid the foundation of supramolecular chemistry. Early studies in molecular recognition by Lehn in the 1970s explored the use of crown ethers as mimics of cyclic peptide ionophores like valinomycin, which bind cations selectively in their internal cavities. Natural ionophores act as antibiotics by upsetting the ionic balance across bacterial cell walls. 

Extensive studies including both inner-sphere and outer-sphere complexation of cations were performed with lasa-locid A, which is a small natural ionophore containing a salicylic acid fragment (Figure 1). The ability of lasalocid to form neutral outer-sphere complexes with species like Co(NH3)(5 +, Cr(bpy)3 ", Pt(bpy)(NH3)2 " " allows one to use it as an ionophore for the membrane transport (including chiroselective transport) of such species. The lasalocid ionophore also was shown to be an efficient carrier for toxic water-soluble metal cations such as Pb + and Cd + across artificial flat-sheet-supported liquid membranes, which represent a potential system for separation of these cations. 

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