Ion-specific carriers

New Tactics in Design of Ion-Specific Carriers Approaches Based on Computer Chemistry and Rare Earth Complex Chemistry... 

New approaches for development of specific carriers for use in liquid membrane are described (i) computer-aided design of cation-specific carriers and (ii) functionalization of rare earth complexes as anion carriers. A new series of Li(I) and Ag(I) ion-specific carriers are successfully designed using MM2, MNDO and density functional calculations. Computer chemistry provides a rational basis for design and characterization of cation-specific carriers of armed crown ether-and podand-types. Lipophilic lanthanide tris(p-diketonates) are shown to be a new class of membrane carriers. They form 1 1 complexes with anionic guests and mediate transport of amino acid derivatives. Since these complexes exhibit different anion transport properties from those of crown ethers, further applications of rare earth complexes offer promising possibilities in the development of specific anion carriers for liquid membrane systems. 

Molecular mechanics calculation (MM) is the computational method most familiar to bench chemists (6, 7). Many kinds of software are on the market and are successfully used to address the conformational properties of various organic molecules. Since the programs have some limitations in dealing with weak interactions, crown ether-alkali metal complexes and related systems have hardly been examined. We applied the "extended MM2 program" (CAChe Scientific, version 3.0) to design Ag(I) ion-specific carriers (8). Because interaction between Ag(I) and donor atoms of the carrier is adequately strong, the MM2 calculation is applicable in such a case. 

Figure 5. Armed crown ethers as Li+ ion-specific carriers.

Figure 29-9. Reactions and intermediates of urea biosynthesis. The nitrogen-containing groups that contribute to the formation of urea are shaded. Reactions and occur in the matrix of iiver mitochondria and reactions , , and in iiver cytosoi. COj (as bicarbonate), ammonium ion, ornithine, and cit-ruiiine enter the mitochondriai matrix via specific carriers (see heavy dots) present in the inner membrane of iiver mitochondria.

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. 

FIGURE 31-7 Mitochondrial carriers. Ions and small molecules enter the intermembrane space, since the outer mitochondrial membrane is not a significant permeability barrier. However, the inner mitochondrial membrane is impermeable to ions except those for which there are specific carriers. Most of the carriers are reversible, as indicated by two-headed arrows. Compounds transported in one direction are indicated in red. The ATP/ADP translocase and the aspartate-glutamate carrier are both electrophoretic their transport is driven in the direction of the mitochondrial membrane potential, as indicated by red arrows. Glutamine is carried into the matrix by an electroneutral carrier. The unimpaired functioning of mitochondrial carriers is essential for normal metabolism. (Adapted with permission from reference [70].)... 

The major transport route of metal ions over a biological membrane is generally assumed to occur over specific carrier ligands or ion channels that are... 

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]. 

Specific carriers in the inner mitochondrial membrane transport ornithine, citrulline, ammonium ion, and HC03 (C02) into and out of the mitochondrial matrix. 

The specific carrier-wave amplitudes (field intensities) which have been found to be effective in producing Ca ion efflux are discussed in terms of tissue properties and relevant mechanisms. The brain tissue is hypothesized to be electrically nonlinear at specific field intensities this nonlinearity demodulates the carrier and releases a 16 Hz signal within ljie tissue. The 16 Hz signal is selectively coupled to the Ca ions by some mechanism, perhaps a dipolar-typ +(Maxwell-Wagner) relaxation, which enhances the efflux of Ca ions. The hypothesis that brain tissue exhibits a slight nonlinearity for certain values of applied RF electric field intensity is not testable by conventional measurements of e because changes... 

Figure 1. Schematic of the two iron transport systems of microorganisms. The high affinity system is comprised of specific carriers of ferric ion (siderophores) and their cognate membrane hound receptors. Both components of the system are regulated by iron repression through a mechanism which is still poorly understood. The high affinity system is invoked only when the available iron supply is limiting otherwise iron enters the cell via a nonspecific, low affinity uptake system. Ferri-chrome apparently delivers its iron by simple reduction. In contrasty the tricatechol siderophore enterobactin may require both reduction and ligand hydrolysis for release...

Hydrogen peroxide diffuses freely through biological membranes, while ferrous atoms are tightly bound to specific carriers. Therefore, the site of "OH formation usually corresponds to the present site of ferrous ions (site specificity of "OH formation ). Thus, concentration of available ferrous ions is considered a limiting factor for the hydroxyl radical formation in vivo. 

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