Ionophore transport

By binding an ion on one side of a lipid bilayer (where the concentration of the ion is high) and releasing it on the other side of the bilayer (where the concentration of the ion is low), an ionophore transports an ion across a cell membrane. 

Uncoupling Oxidative Phosphorylation. The importance of an acidic proton for activity has long been recognized. A mechanism proposed for classical uncouplers (11 ) is that such agents act as ionophores (possibly synergistically with natural ionophores) transporting protons into mitochondria and cations out. In such a case it is reasonable that ionic character is important. The quantitation of the contribution of pKa to activity vis-a-vis partition coefficients has been subjective and conflicting in many cases (1, 12). 

Since carboxylic ionophores transport ions by an electrically silent exchange diffusion mechanism, it is the anionic form of the ionophore which interacts with cations at membrane interfaces Therefore, the lasalocid species most germane for ion complexation within membranes is the free anion Deprotonation of the C25 carboxyl with base results in substantial changes in the absorption and CD spectra from that of the protonated form stabilized by 0.5 equivalents of HCl (cf Fig. 5). The 245 nm absorption band observed for protonated lasalocid intensifies and shifts to 240 nm upon deprotonation while the 317 nm absorption band shifts to 310 nm with little change in intensity. In the CD spectrum, peak I shifts hypso-chromically to 240 nm and intensifies upon deprotonation while peak II shifts bathochromically and diminishes in intensity. 

Faraday s law (p. 496) galvanostat (p. 464) glass electrode (p. 477) hanging mercury drop electrode (p. 509) hydrodynamic voltammetry (p. 513) indicator electrode (p. 462) ionophore (p. 482) ion-selective electrode (p. 475) liquid-based ion-selective electrode (p. 482) liquid junction potential (p. 470) mass transport (p. 511) mediator (p. 500) membrane potential (p. 475) migration (p. 512) nonfaradaic current (p. 512)... 

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. 

Carrier ionophores most move from one side of the membrane to the other, acquiring the transported species on one side and releasing it on the other side. Channel ionophores span the entire membrane. 

Other recent works in this field, studies on the transport of alkali and alkaline earth cations with p-zerr-butyl calix[n]arene esters and amides, were carried out by Arnaud-Neu et al. [20] and Casnati et al. [21]. They prepared 1,3-alternate calix[4]arene-crown-6 as a new class of cesium selective ionophore. 

Active Transport of Ions Using Synthetic Ionophores... 

Proton-driven Transport Systems 2.1 Carboxylic Ionophores... 

Cholanic acid also possesses the ability of transporting cations across a lipophilic membrane but the selectivity is not observed because it contains no recognition sites for specific cations. In the basic region, monensin forms a lipophilic complex with Na+, which is the counter ion of the carboxylate, by taking a pseudo-cyclic structure based on the effective coordination of the polyether moiety. The lipophilic complex taken up in the liquid membrane is transferred to the active region by diffusion. In the acidic region, the sodium cation is released by the neutralization reaction. The cycle is completed by the reverse transport of the free carboxylic ionophore. 

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)... 

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...

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... 

Recently, Shinkai and Manabe achieved the active transport of K+ using a new type of carrier 39 derived from diaza crown ether43, 44). The ionophore forms the zwitter-ionic species 39b, which is most lipophilic among other species (39a, 39c), at about neutral pH region, and it acts as effective ion carrier in the active transport... 

Carboxylic ionophores selectively transport cations by using intramolecular complexation in the uptake process of cations (basic region). A new ion transport system has been developed which incorporates a structural device which assists in the release process by using intramolecular complexation of an [18]crown-6 ring and a primary ammonium ion 48>. The experimental conditions are shown in Fig. 7. All these com-... 

Table 8. Stability constants and competitive transport ability of ionophores (50-57) for potassium and sodium cations...

Fig. 9. Competitive transport of K+ and Na+ using ionophore 58 (Active transport system). (Cited from Ref.58>)...

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