Valinomycin interaction with

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... 

Although some scattered examples of binding of alkali cations (AC) were known (see [2.13,2.14]) and earlier observations had suggested that polyethers interact with them [2.15], the coordination chemistry of alkali cations developed only in the last 30 years with the discovery of several types of more or less powerful and selective cyclic or acyclic ligands. Three main classes may be distinguished 1) natural macrocycles displaying antibiotic properties such as valinomycin or the enniatins [1.21-1.23] 2) synthetic macrocyclic polyethers, the crown ethers, and their numerous derivatives [1.24,1.25, 2.16, A.l, A.13, A.21], followed by the spherands [2.9, 2.10] 3) synthetic macropolycyclic ligands, the cryptands [1.26, 1.27, 2.17, A.l, A.13], followed by other types such as the cryptospherands [2.9, 2.10]. 

Some peptide antibiotics act as trans-membrane ion channels. Vibrational spectroscopy shows that ionophores, such as gramicidin A, valinomycin, nystatin, and amphotericins, interact with phospholipid bilayers (Susi et al., 1979). 

A relevant example of a suitable ionophore is the antibiotic valinomycin, which specifically binds K. Other ionophores have been developed for measurement of, for example, NHj, Ca, Cl . In addition, electrodes have been developed for organic species by using specific ion-pairing reagents in the membrane that interact with ionic forms of the organic compound, e.g. with drugs such as 5,5-diphenylhydantoin. 

K+, located on the inside, interacts with the hydrophilie groups. The matrix side of the inner membrane has a negative potential, so the positively charged valinomycin-K+ complex is drawn inward. The complex uncouples oxidative phosphorylation by decreasing the membrane potential. Unlike valinomycin, it exchanges H" " for K+ across the membrane. Its... 

According to Ovchinnikov and coworkers, the antibiotic activity of valinomycin is due to impairment of alkali ion transport in bacterial membranes217 The main arguments for this theory are (i) None of the synthetic non-complexing analogs has antibiotic activity (ii) enantio-valinomycin has the same antibiotic activity as valinomycin, thus excluding interaction with a stereospecific receptor (iii) valinomycin increases the cation permeability of bacterial membranes (iv) the antimicrobial action of valinomycin depends on the cation composition of the medium. 

Carrier-facilitated transport - Valinomycin, an antibiotic, is an example of a carrier-facilitated transport system. It contains a hydrophobic exterior for interacting with the hydrophobic portion of the membrane s lipid bilayer and an interior designed specifically to accommodate a potassium ion. It transports by the mechanism depicted in Figure 10.20b. 

There are four i C=0 resonances in valinomycin. In the K+ complex the shifts of the ester C=0 are considerable (3.1 to 5.5 ppm downfield) indicating a strong interaction with the metal. The amide shifts are smaller (0.5 to 1.9) (downfield) but also indicate some ion-dipole interaction. Valinomycin and its K complex have also been studied by Fedarko et al. (186) who obtained similar results. 

These 5- l bonds are largely responsible for the oval shape of uncomplexed valinomycin. Moreover, they direct two of the ester carbonyl oxygens toward the surface of the molecule (see Fig. 4). These might serve as initiators of complex formation by interaction with the metal ion prior to the placement of the latter in the ligand cavity. Based on this assumption. Smith and Duax developed a simplified model for the complexation process They proposed that the formation of the initial loose complex with the potassium ion is followed by cleavage of both the 5->l type hydrogen bonds in order to enable all the other ester carbonyl oxygens to interact with the cation and to replace the molecules of its solvation shell one after another. 

Valinomycin dissolved in heptane interacts with aqueous solutions of potassium and sodium picrates. This does not change the interfacial tension as compared to the systems without salt [115]. On the other hand, the study of valinomycin monolayers at the water-air interface proved KCl and NaCl to similarly interact with monolayers only up to a concentration of 0.5 M. At a KCl concentration of 0.7 M the surface potential amounts to 1050 mV, while it is only 550 mV at the same concentration of... 

Several antibiotics show distinct selectivity in their interactions with alkali metal cations (Pioda and Simon, 1969). Two antibiotics in particular, nonactin and valinomycin, associate with potassium ions in preference to sodium ions. It is difficult, by conventional methods, to fabricate an electrode which is selective to potassium in the presence of sodium ions. Using the preferential behavior of these two antibiotics, Simon (1969) was able to produce -selective antibiotic membrane electrodes. 

Molotkovskii, Yu. G. Yakovleva, G. A. Oxonol dye diBa-C4-(5) as a fluorescent probe for membrane potential in chloroplasts and its interaction with valinomycin. Photosynthetica 1985, 19, 493-499. 

The transmembrane potential derived from a concentration gradient is calculable by means of the Nemst equation. If K+ were the only permeable ion then the membrane potential would be given by Eq. 1. With an ion activity (concentration) gradient for K+ of 10 1 from one side to the other of the membrane at 20 °C, the membrane potential that develops on addition of Valinomycin approaches a limiting value of 58 mV87). This is what is calculated from Eq. 1 and indicates that cation over anion selectivity is essentially total. As the conformation of Valinomycin in nonpolar solvents in the absence of cation is similar to that of the cation complex 105), it is quite understandable that anions have no location for interaction. One could with the Valinomycin structure construct a conformation in which a polar core were formed with six peptide N—H moieties directed inward in place of the C—O moieties but... 

Of the neutral ligands described in Section 2, the macrotetrolides and the macroheterobicyclic ligands form nearly spherical complexes and the depsipeptides valinomycin and enniatin B approximately cylindrical ones (Table l)6). Calculations of AGk-values for both kinds of complex show that the discrimination between mono- and divalent cations is dependent not only on the coordination number but also on the overall size and shape of the complexed ligand, because the electrostatic interaction of the complex with the surrounding medium (term AGs in Eq. 

A precise calculation of AGd as a function of the cationic radius would be very difficult because it would involve a complete conformational analysis of a large and complicated ligand system (82). Nevertheless, the dependency of the cation selectivity on steric interactions is capable of illustration. The term AGd can be estimated very crudely by using Hooke s law. As is shown in Fig. 16, ligands that are differentiated only by the radius of their equilibrium cavities can easily discriminate between cations of different size. This may explain why valinomycin and antamanide, two antibiotics with similar coordination spheres (54, 66), do not prefer the same cation (82). As it is no easy task to predict the exact dimensions of the cavity for a proposed ligand, the tailored synthesis of such ligands is conceivable yet problematic. 

This additive procedure was applied for the study of a number of cases including the interaction of cations with the carrier antibiotics valinomycin 184> and nonac-tin 185), the interaction of CH3NH3+ and (CH3)4N+ with amino acids mimicking the active site of a phosphorylcholine antibody186), the interaction of guanine and cytosine with amino acids 181), the interaction of Ca2+ and Mg2-1- with two serine phosphates 188), and the interaction of the channel-forming antibiotic gramicidin A with different cations 189 191>. 

Valinomycin acts as an ion carrier and in some ways could be looked upon as an inverted detergent. Since it is cyclic, it forms a doughnut-type structure where the polar carbonyl oxygens of the ester and amide groups face inside, while the hydro-phobic side-chains of the valine and hydroxyisovalerate units point outwards. This is clearly favoured since the hydrophobic side-chains can interact via van der Waals forces with the fatty Upid interior of the cell membrane, while the polar hydrophilic... 

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