Valinomycin potassium ion

With respect to the carrier mechanism, the phenomenology of the carrier transport of ions is discussed in terms of the criteria and kinetic scheme for the carrier mechanism the molecular structure of the Valinomycin-potassium ion complex is considered in terms of the polar core wherein the ion resides and comparison is made to the Enniatin B complexation of ions it is seen again that anion vs cation selectivity is the result of chemical structure and conformation lipid proximity and polar component of the polar core are discussed relative to monovalent vs multivalent cation selectivity and the dramatic monovalent cation selectivity of Valinomycin is demonstrated to be the result of the conformational energetics of forming polar cores of sizes suitable for different sized monovalent cations. 

Fig. 19. Space filling models of the molecular structure of the Valinomycin-potassium ion complex as originally determined.

Ohnishi, M., and Urry, D. W. Solution conformation of valinomycin-potassium ion complex. Science 168, 1091-1092 (1970). 

Fig. 2. The CPK molecular model of the valinomycin-potassium ion complex. The bare potassium ion is in an octahedral field made up of the polar acyl oxygens of the ester moieties. The side chains give a nonpolar exterior.

In an alternative procedure designed to deal with minute volumes of liquid, Walter38 set up a layer cell based upon the technique employed in instant colour photographic films, Such a cell designed to determine potassium ions made use of two layer assemblies terminating in valinomycin electrodes, so that with a standard potassium chloride solution added to one assembly, and the... 

Neutral carriers are organic complexing agents which are capable of sequestering and transporting ionic species in a hydrophobic organic phase. The antibiotics, valino-mycin and nonactin were the first neutral carriers to be incorporated in an ISE These macrocyclic neutral carriers contain a polar internal cavity and an outer hydro-phobic shell. The excellent selectivity exhibited by valinomycin for potassium ions is... 

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... 

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. 

These substances include primarily depsipeptides (compounds whose structural units consist of alternating amino acid and ar-hydroxy acid units). Their best-known representative is the cyclic antibiotic, valinomycin, with a 36-membered ring [L-Lac-L-Val-D-Hy-i-Valac-D-Val]3, which was isolated from a culture of the microorganism, Streptomyces fulvissimus. Figure 6.13 depicts the structure of free valinomycin and its complex with a potassium ion, the most important of the coordination compounds of valinomycin. 

It appears that Charlton et al.94,95 have discovered the first methods for reversible and continuous optical measurement of the clinically highly important alkali and earth alkali ions. In one approach94 they use plasticized poly(vinyl chloride) along with valinomycin as the ion carrier, and a detection scheme that was later refered to as co-extraction. In their system, potassium ion is extracted into plasticized PVC, and the same quantity of the anionic red dye erythrosine is co-extracted into it. The extracted erythrosine is quantified via absorbance or reflectance. 

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... 

Potentiometric titration has been applied to the determination of potassium in seawater [532-534], Torbjoern and Jaguer [533-544] used a potassium selective valinomycin electrode and a computerised semiautomatic titrator. Samples were titrated with standard additions of aqueous potassium so that the potassium to sodium ion ratio increased on addition of the titrant, and the contribution from sodium ions to the membrane potential could be neglected. The initial concentration of potassium ions was then derived by the extrapolation procedure of Gran. 

Fig. 7.4. Conformations of (a) free valinomycin and (b) of its potassium complex. The carbonyl oxygen atoms, P, P, M and M are in especially exposed positions, so that they can initiate complexation of potassium ion. During complexation, hydrogen bonds 1 and 2 are broken, so that oxygen atoms R and R can take part in the co-ordination of the cation. Further smaller conformation changes allow oxygen atoms Q and Q to partake in formation of new hydrogen bonds, the molecule thus attaining the final round shape (see [44a ]). (By permission of the American Association for Advancement of Science.)...

Uncomplexed valinomycin has a more extended conformation than it does in the potassium complex.385,386 The conformational change results in the breaking of a pair of hydrogen bonds and formation of new hydrogen bonds as the molecule folds around the potassium ion. Valinomycin facilitates potassium transport in a passive manner. However, there are cyclic changes between two conformations as the carrier complexes with ions, diffuses across the membrane, and releases ions on the other side. Tire rate of transport is rapid, with each valinomycin molecule being able to carry 104 potassium ions per second across a membrane. Tlius, a very small amount of this ionophore is sufficient to alter the permeability and the conductance of a membrane. 

Materials with selective binding or transport properties will have a major impact on sensor design and fabrication. Selectivity in either binding or transport can be exploited for a variety of measurement needs. This selectivity can be either intrinsic, that is, built into the chemical properties of the material, or coupled with selective carriers that allow a non-selective material to be converted into a selective one (see the section on recognition chemistry). An example of the latter is the use of valinomycin as a selective carrier in a polyvinyl chloride membrane to form a potentiometric potassium ion sensor. Advances in the fields of gas separation materials for air purification and membrane development for desalinization are contemporary examples illustrating the importance of selective materials. As these materials are identified, they can be exploited for the design of selective measurement schemes. 

Fig. 6.15 (a, b) Neutral ionophore valinomycin with the cavity for binding potassium ion. (c) Charged ionophore di n-octyl phenyl phosphonate used in calcium ion-selective electrodes... 

A host of carriers, with a wide variety of ion selectivities, have been proposed for this task. Most of them have been used for the recognition of alkali and alkaline metal cations (e.g., clinically relevant electrolytes). A classical example is the cyclic depsipeptide valinomycin (Fig. 5.13), used as the basis for the widely used ISE for potassium ion (38). This doughnut-shaped molecule has an electron-rich pocket in the center into which potassium ions are selectively extracted. For example, the electrode exhibits a selectivity for K+ over Na+ of approximately 30,000. The basis for the selectivity seems to be the fit between the size of the potassium ion (radius 1.33 A) and the volume of the internal cavity of the macrocyclic molecule. The hydrophobic sidechains of valinomycin stretch into the lipophilic part of the membrane. In addition to its excellent selectivity, such an electrode is well behaved and has a wide working pH range. Strongly acidic media can be employed because the electrode is 18,000 times more responsive to K+ than to H+. A Nernstian response to potassium ion activities, with a slope of 59mV/pK+, is commonly observed... 

In 1969, Wipf and Simon reported an outstanding potassium ionophore, valinomycin. Valinomycin is an example of a mobile ion carrier. It is a ring-shaped polypeptide that increases the permeability of a membrane to K . The ring has a hydrophobic exterior, made up of valine side chains, and a polar interior, where a single K can fit precisely (see Figure 8.30). In the electrode process, valinomycin transports potassium ions across the membrane by picking up on the solution side of the membrane and releasing it at the transducer surface. 

Figure 8.30. Potassium-valinomycin complex. The potassium ion is embedded in the oxygen-rich inner part of the valinomycin moiety, whereas the hydrophobic side chains stretch out into the lipophilic part of the membrane. Valinomycin is composed of three units of the sequence L-lactate, L-valine, o-hydroxyisovalerate, and D-valine.

Valinomycin can therefore collect a potassium ion from the inner surface of the membrane, carry it across the membrane and deposit it outside the cell, thus disrupting the ionic equilibrium of the cell (Fig. 10.66). Normally, cells have a high con-... 

Valinomycin is specific for potassium ions over sodium ions. One might be tempted to think that sodium ions would be too small to be properly complexed. However, the real reason is that sodium ions do not lose their surrounding water coat very easily and would have to be transported as the hydrated ion. As such, they are too big for the central cavity of valinomycin. 

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