Carrier ionophore

Carrier ionophores most move from one side of the membrane to the other, acquiring the transported species on one side and releasing it on the other side. Channel ionophores span the entire membrane. 

Other mobile carrier ionophores include monensin and nonaetin (Figure 10.39). The unifying feature in all these structures is an inward orientation of polar groups (to coordinate the central ion) and outward orientation of non-... 

A number of substances have been discovered in the last thirty years with a macrocyclic structure (i.e. with ten or more ring members), polar ring interior and non-polar exterior. These substances form complexes with univalent (sometimes divalent) cations, especially with alkali metal ions, with a stability that is very dependent on the individual ionic sort. They mediate transport of ions through the lipid membranes of cells and cell organelles, whence the origin of the term ion-carrier (ionophore). They ion-specifically uncouple oxidative phosphorylation in mitochondria, which led to their discovery in the 1950s. This property is also connected with their antibiotic action. Furthermore, they produce a membrane potential on both thin lipid and thick membranes. 

Monesin binds with sodium ions and carries them across the cell membrane and is called a carrier ionophore. 

The optical sensors are composed of ion-selective carriers (ionophores), pH indicator dyes (chromoionophores), and lipophilic ionic additives dissolved in thin layers of plasticized PVC. Ionophores extract the analyte from the sample solution into the polymer membrane. The extraction process is combined with co-extraction or exchange of a proton in order to maintain electroneutrality within the unpolar polymer membrane. This is optically transduced by a pH indicator dye (chromoionophore)10. 

In the case of co-extraction, a selective anion-carrier (ionophore) extracts the analyte anion into the lipophilic sensor membrane. In order to maintain electroneutrality, a proton is co-extracted into the membrane where it protonates a pH indicator dye contained in the polymer membrane. Due to protonation, the dye undergoes a change in either absorption or fluorescence. (Figure 6 and Tables 13 and 14). 

A different direction in ion-selective electrode research is based on experiments with antibiotics that uncouple oxidative phosphorylation in mitochondria [59]. These substances act as ion carriers (ionophores) and produce ion-specific potentials at bilayer lipid membranes [72]. This function led Stefanac and Simon to obtain a new type of ion-selective electrode for alkali metal ions [92] and is also important in supporting the chemi-osmotic theory of oxidative phosphorylation [69]. The range of ionophores, in view of their selectivity for other ions, was broadened by new synthetic substances [1,61]. 

The question of carrier design was first addressed for the transport of inorganic cations. In fact, selective alkali cation transport was one of the initial objectives of our work on cryptates [1.26a, 6.4]. Natural acyclic and macrocyclic ligands (such as monensin, valinomycin, enniatin, nonactin, etc.) were found early on to act as selective ion carriers, ionophores and have been extensively studied, in particular in view of their antibiotic properties [1.21, 6.5]. The discovery of the cation binding properties of crown ethers and of cryptates led to active investigations of the ionophoretic properties of these synthetic compounds [2.3c, 6.1,6.2,6.4-6.13], The first step resides in the ability of these substances to lipophilize cations by complexation and to extract them into an organic or membrane phase [6.14, 6.15]. 

Table 4 lists some antibiotics that function as ionophores, including some that bind Group IIA cations. Ionophores may be classed as channel formers or carriers by several approaches. A carrier ionophore is dependent on membrane fluidity and so cannot function below the transition temperature of the phospholipids in the membrane, as these are now frozen . The channel formers are much less dependent on membrane fluidity. A channel-forming ionophore cannot function if it fails to span the membrane, and so if an ionophore ceases to function in thicker membranes then it is probably a channel former. The kinetics of ion transport may provide a good indication of the type of ionophore. If an ionophore functions at a rate of more than 104 ions s 1 then it must be a channel former, as this level of ion flux cannot be provided by the diffusion of a carrier complex across the membrane. 

Ionophores are classified as either channel or carrier ionophores. Channel ionophores form channels across the membrane through which ions can diffuse down a concentration gradient. The nature of the channel depends on the ionophore, for example, gramicidin A channels are formed by two gramicidin molecules, N-terminus to N-terminus, each molecule forming a left-handed helix (Figure 7.1(a)). Carrier ionophores pick up an ion on one side of the membrane, transport it across, and release it into the fluid on the other side of the membrane. They usually transport specific ions. For example, valinomycin transports K+ but not Na+ Li+ ions (Figure 7.1(b)). 

Figure 7.1 The general mode of action of ionophores in ion transport, (a) A channel formed by two gramicidin A molecules, N-terminus to N-terminus. (b) The sequence of events in the operation of a carrier ionophore such as valinomycin. Valinomycin is a cyclic peptide consisting of three repeating units with the structure shown...

Several of the polymer membrane anion-selective electrodes described in the literature use quaternary ammonium salts as ion carriers (ionophores) (7). These electrodes respond according to the Hofmeister series (CIO4 > SCN > I > NO3 > Br - N3 > NC>2 > Cl > HCO3 acetate) (2, 5), which is the order of relative lipophilicity of the anions. Therefore, in strict terms, electrodes that respond according to this series could be considered "nonselective". 

A+ = analyte C = neutral carrier ionophore Em = surface potential membrane potential = Em(internal) - m(external). 

Figure 8.29. Ion transport mechanisms through lipid membranes in living cells. There are principally two kinds of transport protein (a) channel proteins, that is, a channelforming ionophore, and (b) carrier proteins, that is, a mobile ion carrier ionophore. The phenomena observed in living cells have much in common with those in artificial polymer membrane ion-selective electrodes. (From Widmer, 1993.)...

Instruments for the measurement of free magnesium in whole blood, plasma, or serum are available commercially. These instruments use ISEs with neutral carrier ionophores, including ETH 5220, ETH 7025, or a proprietary ionophore. Current ionophores or electrodes have insufficient selectivity for magnesium over calcium. Free calcium is simultaneously determined and used chemometrically with the signal from the magnesium electrode to calculate free magnesium concentrations. 

A membrane can be either a liquid or a solid. Its electrical properties arise when it allows transport of an ion of one charge but not that of another. Membranes are usually sufficiently thick that one can distinguish an inside region and two outer boundary regions which are in contact with electrolyte solutions. Two types of membranes are considered here (1) membranes of solid and glassy materials (2) liquid membranes with dissolved ion-exchanging ions or neutral ion carriers (ionophores). In fact all of these membranes are involved in ion exchange. It is important to understand how this process affects the potentials which develop in the system at both sides of the membrane. 

Fig. 2, Structures of some neutral carrier ionophores used in the preparation of liquid and polymer membrane ISEs [From ref. (S5) with permission. Copyright (1982), Pergamon Press.]...

Liquid membrane electrodes (1) classical ion-exchangers (with mobile positively and negatively charged sites as hydrophobic cations or hydrophobic anions), for example K+, Cl selective electrodes, (2) liquid ion-exchanger based electrodes (with positively or negatively charged carriers, ionophores), for example Ca2+, NOJ selective electrodes, (3) neutral ionophore based liquid membrane electrodes (with electrically neutral carriers, ionophores), for example Na+, K+, NI I), Ca2+, Cl selective electrodes. 

The versatility of ISEs was enhanced considerably by the introduction of membranes containing neutral ion carriers (ionophores). The first ISE of this type, with a membrane containing valinomycin and selective for potassium ions, was described by Stefanac and Simon in 1966. There are many liquid chemical systems that interact highly selectively with ions through, e.g., ion exchange, ion association, or solvent extraction. Practically useful ISEs based on these systems and on neutral ionophores have been obtained due to the gradual perfection of the technology of plasticized poly(vinyl chloride) (PVC) matrix membranes. 

Clinical interest in Mg + has increased recently, with the commercialization of Mg " " ISEs based on neutral carrier ionophores for benchtop clinical electrolyte instruments such as AVL and Nova [84]. Magnesium is important for neuronal activity, cardiac excitability, muscular contraction, and blood pressure, among other physiological roles it exists bound to proteins or to small anions and as free Mg +, but has traditionally been measured as total Mg. The recent availability of ISEs combined with the known decrease in dietary magnesium intake in the western world has stimulated clinical research that may have important implications in cardiac care [85] and diabetes [86], as it is now known that ionized Mg (free Mg +) levels can vary, whereas total Mg remains constant. 

Ion-selective electrodes (ISEs) constitute an example of potentiometric sensors that offer several advantages over other analytical techniques for the analysis of environmentally important ions. Specifically, the sensing platform of a membrane-based ISE consists of an ion carrier (ionophore) entrapped within a liquid polymeric membrane. The membrane does offer some interaction with numerous species, but the main interaction governing the selectivity of the sensor is between the analyte/interferences and the ionophore. Once an ionophore that offers the preferred selectivity has been developed and the polymer components that are ionophore-compatible have been optimized, the production of a functional ISE is rather facile and rapid. Presently, ISEs have been reported for several species including metal ions, anions, surfactants, and gases (5). 

SLMs containing selective carriers (ionophores) give higher fluxes and selec-tivities than conventional semipermeable porous polymeric membranes, because diffusion is faster in liquids than in solids. The carrier dissolved in the liquid membrane favours the distribution of one species out of a mixture by specific complexation and extraction, if properly chosen [9]. 

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