Valinomycin, ionophore

Prepare the cocktail for the potassium sensor membrane mixing in a 3mL glass vial the following substances 0.0025 g of valinomycin (ionophore), 0.075 g of poly(vinyl chloride) (PVC), 0.165g of bis(2-ethylhexyl)sebacate (plasticizer), 0.0015 g of potassium tetrakis(4-chlorophenyl)borate (ionic additive) and 1.5 mL of tetrahydrofuran (THF). Cover the vial and shake it well, preferably in an orbital shaker for 30 min in order to dissolve and to homogenize the mixture. The resultant cocktail will suffice to prepare 10 sensors. 

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. 

Valinomycin-based membranes (Table 2.4) have been the predominant choice for potassium sensing in soil and other environmental samples. Considerable research effort has focused on improving the adhesion of the PVC membrane to extend the consistent sensitivity period, and thus, the lifetime of the electrode. Valinomycin ionophores have exhibited strong K selectivity and sensitivity sufficient to quantify variations in the typical range in soil K where additional fertilizer is recommended. ... 

Valinomycin and the Enniatins. Neutral ionophores such as the cycHc dodecadepsipeptide valinomycin [2001-95-8] C H QN O g, (Fig. 8) from StreptomjcesJulvissimus (179), and the cycHc hexadepsipeptides enniatin [11113-62-5] and beauvericin [26048-05-5] from fungi (180—182),... 

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... 

A composite polymer membrane has also been used as an effective amperometric detector for ion exchange chromatography [42] and showed detection limits similar to those obtained with a conductivity detector. An advantage of the amperometric detector based on micro-ITIES over the conductometric detector is that selectively can be tailored by proper choice of the ionophore. For instance, the selectivity of the membrane toward ammonium in the presence of an excess of sodium could be substantially increased by introducing an ammonium-selective ionophore (such as valinomycin) in the gel membrane [42]. 

However, there seems to be some drawback in the solubility or dispersibility of ion-sensing material in silicone rubber. This is mainly because silicone rubber does not contain a large quantity of plasticizer as the membrane solvent, in which neutral carriers can be dissolved easily, unlike in plasticized-PVC ion-sensing membranes. This issue is serious, especially with silicone-rubber membranes containing neutral carriers that show high crystallinity. Valinomycin, a typical ionophore, seems applicable to silicone-rubber-based K" -selec-tive electrodes [7,8,12-14]. Conventional crown-ether-based neutral carriers are also quite soluble in silicone rubber. 

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. 

Other ionophore antibiotics such as gramicidin and valinomycin are channel-forming ionophores because they open pores that extend through the membrane. 

There are several antibiotics called ionophores, most notably nonactin and valinomycin, that coordinate with metal cations in a manner similar to that of crown ether. 

The sensor layer consists of a selective ionophore (e.g. valinomycin for potassium), a lipophilic anionic site (borate) and the cationic PSD. Before interaction with potassium, a lipophilic ion pair between the cationic PSD and borate anion is formed in the polymer layer. When valinomycin (also contained in the layer) selectively extracts potassium into the layer, then the positively charged valinomycin-potassium complex forms an ion pair with... 

Attachment of carbonyl groups to crowns makes these products more akin structurally to the natural ionophore antibiotics such as valinomycin. The dioxo-derivative (179) of 18-crown-6 was prepared in 35% yield by condensation of tetraethylene glycol and diglycolic acid chloride in benzene at 50 °C for 48 hours (Izatt et al., 1977a and 1977b). This product gives binding constants for Na+, K+ and Ba2+ in methanol which are 102—104 times less stable than for the parent crown - the lower constants are a reflection of less favourable AH values for complexation in these... 

Complexation between the alkali metal cations and the flexible crowns in methanol approaches the rates expected for methanol exchange in the inner sphere of these cations. The rates are similar to those for the interaction of the natural ionophores such as valinomycin. 

There appear to be two major ways by which ionophores aid ions to cross membrane barriers. Ionophores such as valinomycin and nonactin enclose the cation such that the outside of the complex is quite hydro-phobic (and thus lipid-soluble). The transport behaviour thus involves binding of the cation at the membrane surface by the antibiotic, followed by diffusion of the complexed cation across the membrane to the opposite surface where it is released. Such carrier type ionophores can be very efficient, with one molecule facilitating the passage of thousands of ions per second. A prerequisite for efficient transport by this type of ionophore is that both the kinetics of complex formation and dissociation be fast. 

Stability constants, measured in methanol solution, for alkaline earth complexes of a number of ionophores are given in Table XVI (280,289,571-577).8 The values for the complexes of valinomycin and enniatin B lie between the values for the crown ethers 15C5 and 18C6 (cf. Section II.C.5 above), for the middle four entries the values are slightly higher. Stabilities of enniatin B complexes show a modest maximum for Ca2+, and of valinomycin complexes show stabilities increasing up to Ba2+ (281). LogAi values for the Ca2+ complexes of acetate, benzoate, and salicylate are between 4.5 and 4.7 in methanol (578) - the... 

A basic property of an ionophore is that it is capable of forming a structure with a lipophilic exterior and polar cavity, as depicted in the scheme of the structure of valinomycin in fig. 7.4. The ionophore cavity must contain less than 12 and preferably 5-8 polar groups. The final complex structure must be relatively stable, which can be attained by strengthening with hydrogen bonds. It should not, however, be too rigid if ion exchange is to be sufficiently rapid [153, 193]. 

Of the K ISEs, the best properties are those of the electrode based on the ionophore valinomycin XXII [51,196], marked by high selectivity for potassium with respect to sodium. Esters of phthalic acid (9,10) are used as membrane solvents and it is preferable for the reasons given in section 3.3 if the membrane contains the potassium salt of hydrophobic anion XV or XVI [119, 166]. The ISE containing cyclic polyether XXV is useful for only some applications [183] because its selectivity for potassium with respect to sodium is much smaller than with the valinomycin ISE. 

Another analytically useful phenomenon in electrolysis at ITIES is ion transfer faciUtated by ionophores present in the non-aqueous phase [8]. If the ionophore is present at a low concentration in the non-aqueous phase and the aqueous phase contains a large concentration of the cation that is bound in a complex with the ionophore (for example as a component of the base electrolyte), then a voltammetric wave controlled by diffusion of the ionophore toward the ITIES or by diffusion of the complex formed away from the ITIES into the bulk of the organic phase appears at a potential lower than the potential of simple cation transfer. The peak height of this wave is proportional to the ionophore concentration in the solution and can be used for the determination (fig. 9.8). This effect has been observed with valinomycin, nonactin, cycUc polyethers and other substances [2,3,23]. The half-wave potential of these waves is... 

A compound that binds to an ion in a manner which greatly facihtates the bound ion s permeabihty across a membrane. Naturally occurring ionophores include both mobile carriers (e.g., valinomycin and nigericin) and channel formers (e.g., gramicidin A). 

The behaviour of valinomycin is typical of a group known as ionophore antibiotics. The antibiotic forms a lipid-soluble complex with K+ which readily passes through the inner mitochondrial membrane, whereas K alone in the absence of valinomycin penetrates only very slowly. Valinomycin binds K+ more strongly than Na. Thus, valinomycin interferes with oxidative phosphorylation in mitochondria by making them... 

An example of an ionophore that is a cage carrier is valinomycin (9.56). This cyclic peptide lactone consists of three molecules each of L-valine, D-a-hydroxyisovaleric acid, and L-lactate. The six highly polarized lactone carbonyl oxygens line the inside of the ring, whereas the nonpolar alkyl groups point to the outside of the molecule. Thus... 

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