Ionophore Reactions

If all the species, that is, the cation, the ligand, and the complex can partition, the Nernst equation can be written either for the ion or the complex  

FIGURE 1.16 Thermodynamic constants for assisted-ion-transfer reactions. 

An early example of TIC transfer was that of K+ facilitated by valinomycin [153] or di-benzo-18-crown-6 [154], 

It would be too long and too tedious to list all the facilitated ion-transfer reactions that have been reported over the years. From aUcali-metal ions to transition metal ions, most cations have been studied with different classes of ionophores ranging from the crown family with N, O, or S electron-donating atoms to caUx-arenes, not to mention all the commercial ionophores developed for ion-selective electrode applications or for solvent extraction. In the case of anions, the number of voltammetric studies reported has been much smaller [155-163], although the field of supramolecular chemistry for anion recognition is developing fast as recently reviewed [164]. 

The concept of assisted ion transfer is, of course, applicable to proton-transfer reactions assisted by the presence of an acid or base, hydrophilic or lipophilic. As pioneered by Kontturi and Murtomaki [165], voltammetry at ITIES has proved to be an excellent method to measure the log values of protonated or deprotonated molecules. Indeed, for therapeutic molecules, the logF values, which are related the Gibbs energy of transfer as shown by Equations 1.11 and 1.12, provide an important physical parameter to assay the toxicity of a molecule. If a molecule is lipophilic, that is, logF 2, it is potentially toxic. In fact, with the concept of ionic distribution diagrams (vide infra) it is even possible to measure the logF values of the neutral associated bases. The application of voltammetry at ITIES to the study of therapeutic molecules has been one of the success stories of electrochemistry at liquid-liquid interfaces. The field has been reviewed over the years [166,167] and very recently by Gulaboski et al. [168]. 

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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. 

An electrode in which an antibody or an antigen/hapten is incorporated in the sensing element is termed an immunoelectrode . The potential response of the immuno-electrode is based on an immunochemical reaction between the sensing element of the electrode and antibody or antigen/hapten in the sample solution. One example of such an electrode is the polymer membrane electrode shown in Fig. 7. The selective response of this electrode to specific immunoglobulins is based on the interaction between antibody in solution and an antigen-ionophore complex in the membrane ... 

Although rum ammonia levels are not routinely measured, it is a useful indicator of Reye s syndrome and should be monitored in newborns at risk of developing hyperammonemia Ammonia is produced in many analytically useful enzyme reactions and the ammonium ISE has been used as the base sensor in several enzyme electrodes (see next section). In addition to valinomycin, other antibiotics such as the nonactin homalogs and gramicidins also behave as ionophores. The nonactin homolo were originally studied for their ability to selectively bind potassiiun ions It was then discovered that ammonium ions were preferred over potassium ions, and the selectivity coefficient Knh+ = 0.12 was reported. Since ammonia is present at fairly low levels in serum, this selectivity is not sufficient to to accurately measure NH4 in the presence of K. An extra measure of selectivity can be gained by using a gas permeable membrane to separate the ammonia gas from the sample matrix... 

The above model can be extended to assisted ion transfer, in which the ion forms a complex with a suitable ionophore. The various mechanisms for such reactions have been classified by Shao et al. [21] and reviewed by Girault [22]. Schmickler [23] has examined the case of transfer by interfacial complexation, which is marked by the following reaction sequence (see Fig. 14) The transferring ion moves from the bulk of solution 1 towards the interface with solution 2, in which it is poorly soluble. At the interface it reacts with an ionophore from solution 2, and then the complexed ion is transferred towards the bulk of solution 2. 

The rate of the ion transfer is governed by the complexation reaction, whose rate constant should not depend on potential since it is a purely chemical reaction. However, the concentrations of the reactant change with potential. Typically, the ionophore is uncharged, so that a change in the potential drop affects only the concentration of the ions at the interface. If the thickness X of the interface is neglected, the concentration of the ion at the interface is given by ... 

Next, the complexation equilibrium at the interface must be taken into account. Under the distribution equilibrium of the primary ion between the aqueous and membrane sides of the interface, the complexation reaction between the primary ion and the ionophore occurs at the membrane side of the interface, i.e.. 

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. 

Besides, potentiometric sensors with ion-selective ionophores in modified poly(vinyl chloride) (PVC) have been used to detect analytes from human serum [128], Cellular respiration and acidification due to the activity of the cells has been measured with CMOS ISFETS [129], Some potentiometric methods employ gas-sensing electrodes for NH3 (for deaminase reactions) and C02 (for decarboxylase reactions). Ion-selective electrodes have also been used to quantitate penicillin, since the penicillinase reaction may be mediated with I or GST. 

Ionophores such as A-23187 and X-14885A are flexible, so despite the need for conformational change, established for A-23187 by a 1H and 13C NMR solution study (556), their complex formation reactions can take place quite quickly as they can change their conformations rapidly as required for sequential bonding to the cation, and thus proceed in a series of energetically not-too-demanding steps. Formation rate constants for the Ca2+ complexes of A-23187 and X-14885A are 6 x 105 and... 

MF effects on FA relatives and healthy donors. (Fanconi anemia is an autosomal recessive disease associated with the overproduction of free radicals, Chapter 31.) It has been shown earlier [215] that FA leukocytes produce the enhanced amount of hydroxyl or hydroxyl-like free radicals, which are probably formed by the Fenton reaction. It was suggested that MF would be able to accelerate hydroxyl radical production by FA leukocytes. Indeed, we found that MF significantly enhanced luminol-amplified CL produced by non-stimulated and PMA-stimulated FA leukocytes but did not affect at all oxygen radical production by leukocytes from FA relatives and healthy donors (Table 21.3). It is interesting that MF did not also affect the calcium ionophore A23187-stimulated CL by FA leukocytes, indicating the absence of the calcium-mediated mechanism of MF activity, at least for FA leukocytes. 

The frequent occurrence of /Thydroxy carbonyl moiety in a variety of natural products (such as macrolide or ionophore antibiotics or other acetogenics) has stimulated the development of stereocontrolled synthetic methods for these compounds. Indeed, the most successful methods have involved aldol reactions.13... 

The equilibrium constant for this reaction depends on the stability constants of the ionophore-M+ complexes and on the distribution of ions in aqueous test solution and organic membrane phases. For a membrane of fixed composition exposed to a test solution of a given pH, the optical absorption of the membrane depends on the ratio of the protonated and deprotonated indicator which is controlled by the activity of M+ in the test solution (H,tq, is fixed by buffer). By using a to represent the fraction of total indicator (Ct) in the deprotonated form ([C]), a can be related to the absorbance values at a given wavelength as... 

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