Ionophores structures

Siderophore-ionophore supramolecular assembly formation via host-guest complexation of the pendant protonated amine arm of ferrioxamine B has been confirmed by X-ray crystallography (Fig. 28) (203). The stability and selectivity of this interaction as a function of ionophore structure, metal ion identity, and counter anion identity were determined by liquid-liquid extraction, isothermal calorimetry, and MS (204 -211). Second-sphere host-guest complexation constants fall in the range 103— 106M-1 in CHC13 and methanol depending on ionophore structure. 

A series of compounds, aimed to be used as fluorescent probes for biological ions, have been synthesized and the fluorescent properties of their free and ion-bound forms were studied. The fluorescent properties of these probes are due to the extended conjugation of chromophores such as substituted coumarins and benzothiazols, whereas their ion chelating properties are due to the presence of ionophores such as [1,10]phenanthrolin-5-amine, N,N-bis(2-pyridinylmethyl)amine, mono- and polyaza macrocyclics, and polycarboxylate moieties. Based on their structural features and their spectral profile, these probes are classified as Photoinduced Electron Transfer (PET) or Photoinduced Charge Transfer (PCT) indicators. Their ion selectivity is discussed in terms of the ionophore structure and the extent of conjugation in their framework. 

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. 

Other mobile carrier ionophores include monensin and nonaetin (Figure 10.39). The unifying feature in all these structures is an inward orientation of polar groups (to coordinate the central ion) and outward orientation of non-... 

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... 

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)... 

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-... 

The carrier used in this transport system is only required to possess the nitrogen atom as a structural unit, which participates in the complexation. From the viewpoint of the simplicity in the structure, the development of new ionophores are expected. 

To achieve the transport of ions against their concentration gradients, the reversible change in the nature of ionophores at the both interfaces of a membrane is necessary, and for this object, many ingenious devices in the structure of ionophores and the transport systems have recently been developed. 

Ionophores constitute a large collection of structurally diverse substances that share the ability to complex cations and to assist in the translocation of cations through a lipophilic interface.1 Using numerous Lewis-basic heteroatoms, an ionophore organizes itself around a cationic species such as an inorganic metal ion. This arrangement maximizes favorable ion-dipole interactions, while simultaneously exposing a relatively hydrophobic (lipophilic) exterior. 

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). 

Calcium-binding proteins, 6, 564, 572, 596 intestinal, 6, 576 structure, 6, 573 Calcium carbonate calcium deposition as, 6, 597 Calcium complexes acetylacetone, 2, 372 amides, 2,164 amino acids, 3, 33 arsine oxides, 3, 9 biology, 6, 549 bipyridyl, 3, 13 crown ethers, 3, 39 dimethylphthalate, 3, 16 enzyme stabilization, 6, 549 hydrates, 3, 7 ionophores, 3, 66 malonic acid, 2, 444 peptides, 3, 33 phosphines, 3, 9 phthalocyanines, 2,863 porphyrins, 2, 820 proteins, 2, 770 pyridine oxide, 3,9 Schiff bases, 3, 29 urea, 3, 9... 

Discuss clearly the structural requirements for designing selective ionophores for ISE work. Give examples of such structures. 

Brooks, G.T. (1992). Progress in structure-activity smdies on cage convnlsants and related GABA receptor chloride ionophore antagonists. In D. Otto and B. Weber (Eds.) Insecticides Mechanism of Action and Resistance. Newcastle npon Tyne, UK Intercept Press, 237-242. 

A. V., Yao, X., Doucet, J. P., Fan, B., Hoonakker, F., Fourches, D., Jost, P., Lachiche, N., Vamek, A. Benchmarking of linear and nonlinear approaches for quanfitafive structure-property relafionship studies of metal complexafion with ionophores. J. Chem. Inf. Model. 2006, 46, 808-819. 

Liquid membrane type ion-seleetive electrodes (ISEs) provide one of the most versatile sensing methods because it is possible to customize the sensory elements to suit the structure of the analyte. A wealth of different synthetic and natural ionophores has been developed, in the past 30 years, for use in liquid membrane type ISEs for various inorganic and organic ions [1], In extensive studies [2-4], the response mechanism of these ISEs has been interpreted in terms of thermodynamics and kinetics. However, there have been few achievements in the characterization of the processes occurring at the surface of ISEs at molecular level. 

FIG. 2 Structures of the ionophores 1-4. 1 =dibenzyl-14-crown4 2 = bis(benzo-15-crown-5) 3 =dibenzo-18-crown-6 4 = dibenzo-24-crown-8 these ionophores are selective for Li+, K+, and Na, respectively. (From Ref 15.)... 

If the photoequilibrium concentrations of the cis and trans isomers of the photoswitchable ionophore in the membrane bulk and their complexation stability constants for primary cations are known, the photoinduced change in the concentration of the complex cation in the membrane bulk can be estimated. If the same amount of change is assumed to occur for the concentration of the complex cation at the very surface of the membrane, the photoinduced change in the phase boundary potential may be correlated quantitatively to the amount of the primary cation permeated to or released from the membrane side of the interface under otherwise identical conditions. In such a manner, this type of photoswitchable ionophore may serve as a molecular probe to quantitatively correlate between the photoinduced changes in the phase boundary potential and the number of the primary cations permselectively extracted into the membrane side of the interface. Highly lipophilic derivatives of azobis(benzo-15-crown-5), 1 and 2, as well as reference compound 3 were used for this purpose (see Fig. 9 for the structures) [43]. Compared to azobenzene-modified crown ethers reported earlier [39 2], more distinct structural difference between the cis... 

Dobler, M., Ionophores and Their Structures. Wiley, New York, 1981. 

Especially sensitive and selective potassium and some other ion-selective electrodes employ special complexing agents in their membranes, termed ionophores (discussed in detail on page 445). These substances, which often have cyclic structures, bind alkali metal ions and some other cations in complexes with widely varying stability constants. The membrane of an ion-selective electrode contains the salt of the determined cation with a hydrophobic anion (usually tetraphenylborate) and excess ionophore, so that the cation is mostly bound in the complex in the membrane. It can readily be demonstrated that the membrane potential obeys Eq. (6.3.3). In the presence of interferents, the selectivity coefficient is given approximately by the ratio of the stability constants of the complexes of the two ions with the ionophore. For the determination of potassium ions in the presence of interfering sodium ions, where the ionophore is the cyclic depsipeptide, valinomycin, the selectivity coefficient is Na+ 10"4, so that this electrode can be used to determine potassium ions in the presence of a 104-fold excess of sodium ions. 

A number of substances have been discovered in the last thirty years with a macrocyclic structure (i.e. with ten or more ring members), polar ring interior and non-polar exterior. These substances form complexes with univalent (sometimes divalent) cations, especially with alkali metal ions, with a stability that is very dependent on the individual ionic sort. They mediate transport of ions through the lipid membranes of cells and cell organelles, whence the origin of the term ion-carrier (ionophore). They ion-specifically uncouple oxidative phosphorylation in mitochondria, which led to their discovery in the 1950s. This property is also connected with their antibiotic action. Furthermore, they produce a membrane potential on both thin lipid and thick membranes. 

It is now recognised that a wide range of organic molecules, collectively termed ionophores 185,186) or complexones 187), are able to facilitate ion (usually cation) transport. Two major mechanisms have been revealed for this process, namely the involvement of transmembrane ion carriers and transmembrane pores or channels (see Fig. 19). The majority of ionophores studied to date are natural antibiotics and their synthetic analogues which are, on a biological scale, comparatively small molecules lending themselves to study outside the biological system. In contrast far less is known about the molecular structures involved in normal transport processes. Such molecules are likely to be more complex or present in small amounts and may require... 

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