Synthesized ionophores

Ion-selective electrode research for biomedical analysis is no longer the relatively narrow, focused field of identifying and synthesizing ionophores for improved selectivity and the integration of ion-selective electrodes into clinical analyzers and portable instruments. These efforts have matured now to such an extent that they can teach valuable lessons to other chemical sensing fields that are just emerging technologies. 

Is it possible to synthesize ionophores specific for anions These molecules would be of great importance in practical applications, especially in medicine. If they could be made stereospecific they could, in addition, offer new insights into enzyme and carrier mechanisms since they can be regarded as primitive models of such molecules. 

The need for better ionophores will make sure that the work of those who practice host-guest chemistry will continue to be much valued in ion-selective potentiometry. Care must, however, be taken to ensure that reported selectivities are reproducible and accurately reflect the thermodynamics of complex stoichiometries and complex stabilities. There is an ever increasing number of reports on ISEs based on new ionophores, but not all reported work reflects on the full complexity and potential of the often hard to synthesize ionophores. It is the hope of the authors that this chapter has contributed to span the gap between on one hand (too) simple introductions to ISEs and, on the other hand, the intimidating plethora of recent publications written for the specialist. 

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... 

Certain microbes synthesize small organic molecules, ionophores, that function as shuttles for the movement of ions across membranes. These ionophores contain hy-drophihc centers that bind specific ions and are surrounded by peripheral hydrophobic regions this arrangement allows the molecules to dissolve effectively in the membrane and diffuse transversely therein. Others, Hke the well-smdied polypeptide gramicidin, form channels. 

We recently synthesized several reasonably surface-active crown-ether-based ionophores. This type of ionophore in fact gave Nernstian slopes for corresponding primary ions with its ionophore of one order or less concentrations than the lowest allowable concentrations for Nernstian slopes with conventional counterpart ionophores. Furthermore, the detection limit was relatively improved with increased offset potentials due to the efficient and increased primary ion uptake into the vicinity of the membrane interface by surfactant ionophores selectively located there. These results were again well explained by the derived model essentially based on the Gouy-Chapman theory. Just like other interfacial phenomena, the surface and bulk phase of the ionophore incorporated liquid membrane may naturally be speculated to be more or less different. The SHG results presented here is one of strong evidence indicating that this is in fact true rather than speculation. 

Various types of research are carried out on ITIESs nowadays. These studies are modeled on electrochemical techniques, theories, and systems. Studies of ion transfer across ITIESs are especially interesting and important because these are the only studies on ITIESs. Many complex ion transfers assisted by some chemical reactions have been studied, to say nothing of single ion transfers. In the world of nature, many types of ion transfer play important roles such as selective ion transfer through biological membranes. Therefore, there are quite a few studies that get ideas from those systems, while many interests from analytical applications motivate those too. Since the ion transfer at an ITIES is closely related with the fields of solvent extraction and ion-selective electrodes, these studies mainly deal with facilitated ion transfer by various kinds of ionophores. Since crown ethers as ionophores show interesting selectivity, a lot of derivatives are synthesized and their selectivities are evaluated in solvent extraction, ion-selective systems, etc. Of course electrochemical studies on ITIESs are also suitable for the systems of ion transfer facilitated by crown ethers and have thrown new light on the mechanisms of selectivity exhibited by crown ethers. 

Two new chromogenic crown ether derivatives based on an identical design principle have been synthesized. The lipophilic KBC-002 shown in Figure 23 is a useful new chromo- ionophor for the highly selective calcium determination with cation exchange type optode53. 

The Ba ISE containing the acyclic membrane carrier nonylphenoxy-poly(ethylenoxy)ethanol described by Levins [123] opened new fields in ion-selective electrodes based on synthetic acyclic ionophores. Simon and coworkers synthesized several hundred substances [3] that can be used for ISEs to determine alkaline earth ions, primarily Ca [4], and also [190], etc. (for a review, see [133, 154]). A natural ionophore for calcium is the antibiotic,... 

The advent of the polyether antibiotics with the challenging aspect of stereocontrolled construction of the substituted tetrahydrofuran units has greatly extended the chemistry of this oxygen heterocycle. The nonactins (194), lasalocid A (195) and monensin (196) are among the ionophores for which syntheses have been achieved. Detailed reviews on synthesis of reduced furans are available (65HOU(6/3)l, 80H(14)1825). 

A polymeric stack of macrocycles has been synthesized [6.72] and a cyclodextrin-based model of a half-channel has been reported [6.73]. Channel-type conduction of Na+ ions has been reported for a tris-macrocyclic ligand [6.74]. A derivative of the acyclic polyether ionophore monensin forms lithium channels in vesicles [6.75a], which may be sealed by diammonium salts [6.75b]. 

Particular attention should be paid to ionophore A23187, a polyether antibiotic produced by Streptomyces organisms, which also synthesize a range of other polyether antibiotics. This ionophore has been used extensively in the mediation of calcium transport in a diverse range of processes. The structure of A23187 is included in Figure 5. Its absolute configuration is known.1 3... 

Claisen rearrangements of silyl ketene acetals have been used in numerous syntheses, including the synthesis of the ionophore antibiotic Calcimycin outlined in Figure Si3.12. 

All acrylate- and methacrylate-based membranes were synthesized by photopolymerization on top of the polyHEMA interlayer. The resulting FETs showed in the absence of an ionophore a cation response of 36-54 mV/decade and therefore we concluded that residual anionic groups must be present. Titration of the ACE monomer with KOH solution indicated the presence of 7.5 x Id5 eq. acid.g"1 ACE monomer. As shown in Table 2 the ACE was chemically modified by reaction of the hydroxyl group. In this way acetyl, pentanoyl, and hydroxy... 

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