NA Selectivity

Recently, Deligoz and Yilmaz [24,25] described the preparation of two polymeric calix[4]arene tetra esters (Scheme 4) and their Na -complexation. Based on phase-transfer experiments with these compounds using alkali picrates in water-dichloromethane, they confirmed that polymers are as Na selective as monomers. 

Ator NA Selectivity in generalization to GABAergic drugs in midazolam-trained baboons. Pharmacol Biochem Behav 75 435 43, 2003... 

It has been long believed that a lithium ion-selective electrode would render obsolete the flame photometer in the clinical laboratory. Lithium is administered to manic depressive psychiatric patients. Since the therapeutic range (0.5-1.5 mM) is quite close to the toxic range (>2 mM), it must be closely monitored. Most of the iono-phores propo d to date have not met the Li" /Na selectivity required for an interference-free assay. However, it has been reported that calibration in the presence of 140 mMNa permitted the analysis of Li in serum The errors observed are due to fluctuations in the Na concentrations in the sample. More selective ionophores would certainly improve the accuracy of this method. 

FIG. 5 Potential response of silicone-rubber-membrane Na -selective electrodes based on neutral carriers (5) (O), (2) ( ), and bis(12-crown-4) (A)- (From Ref. 22.)... 

FIG. 11 Potential response of Na+-selective electrodes based on silicone-rubber membranes modified chemically by triethoxysilylated calix[4]arene (8) (O) without anion excluder ( ) with TFPB ( ) modified chemically by triethoxysilylated tetraphenylborate (9) as well. (From Ref. 44.)... 

The Na -selective electrodes based on silicone-rubber membranes modified chemically by (8) and (9), were also investigated for Na assay in control serum and urine [22]. The found values for the Na concentrations in both of the serum and urine samples are in good agreement with their corresponding actual values with a relative standard deviation of about 1%. These results suggest that the Na -selective electrodes based on silicone-rubber membranes modified chemically by calix[4]arene neutral carrier (8) are reliable on assay in human body fluid. 

Fig. 16. The antibiotic ligands (a) monensin, which binds Na+ selectively, and (b) valinomycin and (c) enniatin-B, which bind K+ selectively.

The sequence of the selectivities towards cations is also solvent dependent for dibenzo-18-crown-6 [11] the sequence is K+ > Na+ > Rb+ > Cs+ in water, methanol, dimethylformamide and dimethyl sulfoxide (Dechter and Zink, 1976 Srivanavit et al., 1977), whereas it is Na+ > K+ > Rb+ > Cs+ in acetonitrile (Hofmanova et al., 1978). A reversal of the K+/Na+ selectivity on going to apolar aprotic solvents was also observed for fluorenyl salts (Wong et al., 1970). Whereas for alkali cations the sequence of binding constants and enthalpies are the same in water (Izatt et al., 1976a), they differ considerably in methanol/water mixtures (Izatt et al., 1976b), dimethyl sulfoxide and acetone (Arnett and Moriarity, 1971). 

A tribenzocrown has been covalently linked to coumarine to give PCT-20. This complexing moiety is expected to be selective for K+. The K+/Na+ selectivity is only 2 in acetonitrile, but 20 in ethanol. 

Kca+Na+ Selectivity between calcium ions and sodium ions in a cationic resin ... 

If the notion that 15-crown-5 is selective for Na" " is correct, then Ks for the interaction 15-crown-5 Na+ should be greater than the interaction 15-crown-5 K+. We see from Table I that log Ks for the sodium interaction is 3.24 (1,740) compared to 3.43 (2,690) for potassium. An alternate definition of Na+-selectivity might be that 15-crown-5 binds Na" " more strongly than 18-crown-6 binds Na" ". The log Ks values for this pair of interactions is, respectively, 3.24 (1,740) vs. 4.35 (22,400). Clearly, 15-crown-5 is not selective for Na" " and the simple "hole-size rule does not correctly account for the results. 

Best overall selectivity for all M /Mf couples is shown by compound 30, [2.2.2], However a given selectivity may be increased by structural modifications. For instance the K+/Rb+ selectivity increases markedly from 30 to 36. Indeed the introduction of the benzo ring is expected to decrease the cavity size (shorter O. .. O distance) and to increase ligand rigidity (rotation about the central C—C bond in the benzo bridge is frozen). Both effects hinder the cavity dilatation required for Rb+ inclusion on the other hand, they also favour the smaller Na+ cation with respect to K+, thus diminishing the K+/Na+ selectivity of 36 as compared with 30. 

A comparison of the selectivities displayed by 15 and 19 is also instructive. Despite its higher number of O. . . K+ interactions the [19, K+] complex is less stable than the [15, K+] complex the K+/Na+ selectivity of 19 is, however, much higher than that of 15. This is clearly linked to the ability of 19 to change conformation and wrap around the K+ cation. 

The flexible macrobicyclie ligands 31—33 display high K+/Na+ selectivity (300—600), but weak K+/Rb+, Cs+ selectivities. On the other hand, the more rigid ligand 30 shows a K+/Na+ selectivity similar to those of the flexible ligands 19 and 31—33, but it also has appreciable K+/Rb+, Cs+ selectivity. 

Quite opposite is the case of ligand 19 whose conformation is very different in the free and complexed states (Figures 6). A study of the carrier properties of this ligand would be interesting since it may be an efficient carrier while retaining appreciable K+/Na+ selectivity.7)... 

The capacity of inositol orthoformate derivatives 124 and 125 for binding to alkali metal ions was studied by electrospray ionization mass spectrometry (ESI-MS) gas-phase measurements <2001JOC8629>. The [5.5.5]-iono-phore 125 n = 3) possessed the highest Li /Na selectivity and the best affinity for Li. The results obtained proved to be in agreement with the size-fit concept. Other factors which influence the complexation are the orientation of the oxygen atoms, which are able to bind to metal, the basicity, and the polarizability of the heteroatoms around the perimeter of the binding cavity. 

Both Table II and (8) show clearly that membrane selectivities may depend highly on the concentration cs of the carrier within the membrane phase. Although the ligands 1023 and 1149 induce Ca2+- and Na+-selectivities, respectively, in bilayer membranes,50,51 the correlation of these selectivities with those of bulk membranes is not as pronounced as indicated in Fig. 2.50 In bulk membrane experiments Ca2+ and Na+ are found to be preferred by 10 and 11, respectively.23,49 52 For a more careful comparison of the selectivities, the concentration cs of the ligand in the membrane phase should be adjusted. 

Fig. 4. Transport selectivity Kjj and potentiometric selectivity Kj j of a Na+-selective neutral carrier membrane using ligand 11. Experimental coefficients fCNaM obtained with (2) and (11) respectively given for different cations M. Membrane composition 32wt.% polyvinyl chloride, 65 wt.% dibutyl sebacate, 3wt.% carrier //. Thickness of membrane = 100 p.m. Current density approx. 0.1 p.Amm 2.

I would like to extend Prof. Simon s characterizations of these beautiful new molecules to include a description of the effects on lipid bilayers of his Na+ selective compound number 11, which my post-doctoral student, Kun-Hung Kuo, and I have found to induce an Na+ selective permeation across lipid bilayer membranes [K.-H. Kuo and G. Eisenman, Naf Selective Permeation of Lipid Bilayers, mediated by a Neutral Ionophore, Abstracts 21st Nat. Biophysical Society meeting (Biophys. J., 17, 212a (1977))]. This is the first example, to my knowledge, of the successful reconstitution of an Na+ selective permeation in an artificial bilayer system. (Presumably the previous failure of such well known lipophilic, Na+ complexing molecules as antamanide, perhydroan-tamanide, or Lehn s cryptates to render bilayers selectively permeable to Na+ is due to kinetic limitations on their rate of complexation and decomplexation). 

I would also like to reemphasize the noncyclic character of these molecules, which I believe provides the way to circumvent the kinetic limitations on the rates of complexing and decomplexing such strongly hydrated ions as Na+, Li+, Ca2+, which I suspect has stood in the way previously of translating the complexing selectivity of macrocyclic com-plexones into effective mediators for the selective permeation of these ions across the bilayer membrane. This may already offer a clue to the architecture of the Na+ selective sites of the cell membrane. 

A series of synthetic 32-membered ring macrotetrolides related to the actins have been prepared and show cation transfer ability. The K+/Na+ selectivity is however inferior to that of the actins and cyclic polyethers.563... 

The equilibrium constant is called the selectivity coefficient, because it describes the relative selectivity of the resin for Li+ and Na+. Selectivities of polystyrene resins in Table 26-3 tend to increase with the extent of cross-linking, because the pore size of the resin shrinks as cross-linking increases. Ions such as Li+, with a large hydrated radius (Chapter 8 opener), do not have as much access to the resin as smaller ions, such as Cs+, do. 

Extraction of Cesium and Sodium Cs/Na Selectivity and Competitive Extraction of Cesium in the Presence of an Excess of Sodium... 

Several classes of synthesized calixarenes bearing several moieties (ether, ester, and amide derivatives), were tested for the extraction of strontium picrates (from aqueous solutions into dichloromethane).128 Only a few of them show appreciable extraction levels. The p-i-butyl calix[6]arene hexa(di-/V-ethyl)amide (CA4) shows a very high extraction level of alkaline earth cations with respect to alkali metal cations. Moreover, dealkylation of the calix[6]arene hcxa(di-/V-cthyl)amidc (CA5) decreases the extraction of both sodium and strontium. As this decrease is much more important for sodium than for strontium, the Sr/Na selectivity, which increases from 3.12 to 9.4, is better than that achieved for DC18 derivative under the same conditions (8.7). These results were confirmed by extraction of strontium (5 x 10 4 M) from 1 M HN03 solutions, where it was found that p-t-butyl calix[4]arene tetra(di-N-ethyl) amide (CA2) (10 2 M in NPOE) extracts only sodium (DNa = 12.3, DSl < 0.001). 

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