Calcium -selective ionophore

Calcium-selective ionophore ETH 1001 Lipophilic anionic additive potassium... 

Calcium-selective electrodes have long been in use for the estimation of calcium concentrations - early applications included their use in complexometric titrations, especially of calcium in the presence of magnesium (42). Subsequently they have found use in a variety of systems, particularly for determining stability constants. Examples include determinations for ligands such as chloride, nitrate, acetate, and malonate (mal) (43), several diazacrown ethers (44,45), and methyl aldofuranosides (46). Other applications have included the estimation of Ca2+ levels in blood plasma (47) and in human hair (where the results compared satisfactorily with those from neutron activation analysis) (48). Ion-selective electrodes based on carboxylic polyether ionophores are mentioned in Section IV.B below. Though calcium-selective electrodes are convenient they are not particularly sensitive, and have slow response times. 

W.E. Morf, K. Seiler, B. Rusterholz and W. Simon, Design of a calcium-selective optode membrane based on neutral ionophores, Anal. Chem., 62 (1990) 738-742. 

By definition, the uncoupling effect of certain flavonoids should be independent of their inhibitory effects on mitochondrial respiration or FoFi-ATPase, suggesting an additional mode of action of flavonoids against mitochondrial function. A collapse of the transmembrane potential is likely under conditions in which the permeability barrier created by the mitochondrial inner membrane is compromised (as occurs in the presence of ionophores). Calcium, phosphate, oxidative stress, adenine nucleotide depletion, and membrane depolarization can induce such a nonspecific increase in the permeability of the inner membrane, in an event called the mitochondrial permeability transition (MPT) [30,34]. The MPT can be selectively inhibited by cyclosporin A and is believed to involve the assembly of a multiprotein complex to form a nonspecific pore that spans the inner and outer mitochondrial membranes. The latter assembly is referred to as the permeability transition pore complex (PTPC) (Fig. 1). Its exact composition is unknown, but appears to comprise cyclophilin D, ANT, the voltage-dependent anion channel (porin), and a benzodiazepinebinding site [10,30,34]. 

Anthraquinone, 1-hydroxy-calcium aluminum chelate compound, 1,2 metal complexes dyes, 6,86 Antiarthritis drugs labelled gold compounds, 6, 969 metal complexes, 6,758 Antibiotic M139163,2, 974 Antibiotics ionophoric, 6, 553 metal complexes selective binding, 6, 552... 

Many other cyclic and noncyclic organic carriers with remarkable ion selectivities have been used successfiilly as active hosts of various liquid membrane electrodes. These include the 14-crown-4-ether for lithium (30) 16-crown-5 derivatives for sodium bis-benzo-18-crown-6 ether for cesium the ionophore ETH 1001 [(R,R)-AA -bisd l-ethoxycarbonyl)undecyl-A,yVl-4,5-tctramcthyl-3,6-dioxaoctancdiamide] for calcium the natural macrocyclics nonactin and monensin for ammonia and sodium (31), respectively the ionophore ETH 1117 for magnesium calixarene derivatives for sodium (32) and macrocyclic thioethers for mercury and silver (33). 

Potentiometry is the measurement of the potential at an electrode or membrane electrode, so the detector response is in units of volts. The potentio-metric response tends to be slow, so potentiometry is used infrequently in analysis.47 One example is the use of a polymeric membrane impregnated with ionophores for the selective detection of potassium, sodium, ammonium, and calcium 48 In process chromatography, potentiometry may be used to monitor selected ions or pH as these values change over the course of the gradient. 

Two new chromogenic crown ether derivatives based on an identical design principle have been synthesized. The lipophilic KBC-002 shown in Figure 23 is a useful new chromo- ionophor for the highly selective calcium determination with cation exchange type optode53. 

Ionophore-based solvent polymeric membranes were used as sensing layers for the development of LAPS selective for lithium [70], potassium and calcium ions [71]. Anion-selective LAPS for the determination of nitrate and sulfate ions were described [72],... 

An ionophore is a compound that is capable of selectively carrying ions across a membrane. The ion fits into a specific binding site in a molecule that is hydrophobic enough to cross the membrane. There are calcium-specific ionophores, proton ionophores, sodium ionophores, etc. 

Bychkova and Shvarev [16] recently prepared nanosensors (0.2-20 pm) for sodium, potassium and calcium using the precipitation method. Similarly to the previous works, the plasticized poly(vinyl chloride) included a phenoxazine chro-moionophore, a lipophilic ion exchanger and a cation-selective ionophore. The dynamic range of the very selective sensors was 5 x 10 4-0.5 M for sodium, 1 x 10 5-0.1 M for potassium and 2 x 10 4 - 0.05 M for calcium. As was demonstrated by Bakker and co-workers [45] a particle caster can be used can be used for preparation of much larger beads (011 pm). 

In biomedical applications, the ranges of ion concentration are higher by several orders of magnitude. For instance, the abovementioned calcium probes for living cells cannot be used because the dissociation constant is so low that they would be saturated. Special attention is thus to be paid to the ionophore moiety to achieve proper selectivity and efficiency of binding. For instance, at present there is a need for a selective fluorescent probe for the determination of calcium in blood which could work in the millimolar range in aqueous solutions so that optodes with immobilized probes on the tip could be made for continuous monitoring calcium in blood vessels. 

The Ba ISE containing the acyclic membrane carrier nonylphenoxy-poly(ethylenoxy)ethanol described by Levins [123] opened new fields in ion-selective electrodes based on synthetic acyclic ionophores. Simon and coworkers synthesized several hundred substances [3] that can be used for ISEs to determine alkaline earth ions, primarily Ca [4], and also [190], etc. (for a review, see [133, 154]). A natural ionophore for calcium is the antibiotic,... 

The ion selectivities displayed by these antibiotics are lower than those of the neutral ionophores, and are given in Table 11. Many studies have been made on the properties of these ionophores, particularly with reference to the calcium-transporting abilities of A 23187 (146) and lasolocid (145). The search for new antibiotics is ongoing and there is constant addition to a list of about 50 distinct polyether antibiotics which have been isolated from various streptomycetes. Representative structures will be discussed here to illustrate the nature of complexation with alkali and alkaline earth metal cations. 

There are two kinds of ionophores charged ones, which are called liquid ion exchangers, and neutral carriers. Because they are mobile in both the free and in the complexed form, mobilities of all species are again part of the selectivity coefficient together with the ion-exchange equilibrium constant. The best-known neutral ionophore is valinomycin (Fig. 6.15a) which shows a 1,000 1 selectivity for K+ in preference to Na+ and no pH dependence. In its uncomplexed form, it is electrically neutral. A better-known representative is di(n-octyl phenyl) phosphonate (Fig. 6.15c), which shows good selectivity for calcium ion and is relatively pH insensitive. 

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... 

Does the signal in an opt(r)ode for calcium ion depend on the thickness of the membrane containing the calcium chromophore How does it compare with the thickness dependence of the signal in a calcium ion-selective electrode containing calcium ionophore ... 

The development of a sensor for ionized magnesium turned out to be one of the most difficult challenges of recent years. Several carriers have been designed for this purpose but none have been satisfactory. The first report of a successful measurement of ionized magnesium in an automated clinical analyzer (Thermo, prev. KONE) was published only in 1990 [30]. The ionophore ETH 5520 was used as the active compound. Two other carriers have been used since then ETH 7025 (Roche, former AVL), and a derivative of 1,10-phenenthroline (Nova). All of the magnesium sensors are based on a plastic membrane. Numerical compensations of the influence of calcium ion and the ionic strength are used due to insufficient selectivity of the magnesium sensors. 

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