Cation carriers

A second source of inspiration for studying the open-chained equivalents of crown ethers was the observation that a number of naturally occurring antibiotics enhance cation transport and bear a structural similarity to open-chained crown ethers. A number of groups have examined neutral synthetic ionophores and a variety of novel cation carriers is now available. This is discussed in Sect. 7.4, below. 

It has been observed that the best neutral cation carriers have the synclinal arrangement of binding atoms in the backbone (see 7.2). Syntheses of both an aliphatic and aromatic ligand are shown below in Eqs. (7.12) and (7.13). 

Recently, several other groups have contributed synthetic cation carriers. In particular, Vogtle has reported a large number of structures in this effort (see also Sect. 

This system has characteristic in ingeneous combination of a redox pump and the selective complexation of cation by the macrocyclic ligand. It must be noted that this new system is very promising from the point of view of extending the scope of the selection of the cation carriers, since any carrier can be employed so long as it has selectivity for a special cation and has enough stability toward redox system. 

Fig. 10. Representation of the mechanism of redox driven K + transport using an electron and a cation carrier. (59-Ni°) and (59-Ni ) are the oxidized and reduced form of the electron carrier, the nickel bis-dithiolene complex 59 [] and [K+] are dicyclohexyl-18-crown-6 and its K+ complex. (Cited from Ref. 59>)...

Chrisstoffels, L. A. J. de Jong, F. Reinhoudt, D. N. Sivelli, S. Gazzola, L. Casnati, A. Ungaro, R. Facilitated transport of hydrophilic salts by mixtures of anion and cation carriers and by ditopic carriers. J. Am. Chem. Soc. 

Figure 19.3 The effectiveness of cBSA as an immunogen can be seen by the comparison of specific antibody response in mice to AV coupled to both nBSA cBSA. The quantity injected was standardized according to the amount of AV present. The cationized carrier results in higher concentrations of antibody produced against the peptide than the immunogen made with nBSA.

In this study, we report the release properties of two new polyelectrolyte materials poly(acrylamido-methyl-propanesulfonate) (PAMPS) and poly (diallydimethyl ammonium chloride) (PDADMAC), which were used as anionic and cationic carriers, respectively, for oppositely charged drugs. These polymers proved to be very promising and practical as erodible carriers for controlled drug delivery as they are available commerically. Binding ionic moieties to the linear polymer backbone can be done by a simple mixing process. 

IV. 10. Cation Transport. Design of Selective Cation Carriers... 

The design of a specific cation carrier thus presents two main additional requirements lipophilicity and a compromise between thermodynamics and kinetics of complexation. 

Table 1. X-ray crystal structures of complexes of alkali cation carrier antibiotics (53)... 

Nasrallah HA, Varney N, Coffman JA, et al Opiate antagonism fails to reverse post-ECT cognitive deficits. J Clin Psychiatry 47 555-556, 1986 Nasrallah HA, Coffman JA, Olson SC Structural brain-imaging findings in affective disorders an overview. J Neuropsychiatry Clin Neurosci 1 21-26, 1989 Naylor GJ, Smith AHW Defective genetic control of sodium-pump density in manic depressive psychosis. Psychol Med 11 257-263, 1981 Naylor GJ, McNamee HB, Moody JP Erythrocyte sodium and potassium in depressive illness. J Psychosom Res 14 173-177, 1970 Naylor GJ, McNamee HB, Moody JP Changes in erythrocyte sodium and potassium on recovery from depressive illness. Br J Psychiatry 118 219-223, 1971 Naylor GJ, Dick DAT, Dick EG, et al Lithium therapy and erythrocyte membrane cation carrier. Psychopharmacologia 37 81-86, 1974 Naylor GJ, Smith AHW, Dick EG, et al Erythrocyte membrane cation carrier in manic-depressive psychosis. Psychol Med 10 521-525, 1980... 

The mechanism by which cations are transported across a membrane is represented in Figure 18a. A cation-carrier complex is initially formed at the interface. This lipophilic species then diffuses across the membrane as an ion pair and dissociates at the other interface to water soluble ion pair and membrane-soluble carrier. The final step is back diffusion of the free carrier to the initial interface. The factors which influence transport rates and selectivity have been the subject of much research (79PAC979, B-81MI52102). 

Figure 18 (a) Mechanism of ion pair transport mediated by a cation carrier (b) plot of initial transport rates (V) of cation picrates as a function of the logarithm of the stability constants... 

Because of the complex equilibria involved (Figure 18a), transport rates depend on the delicate balance of many factors including complexation properties and lipophilicity of the carrier, the cation and anion being transported, and the nature of the membrane species itself. Importantly, transport rates are not directly proportional to the cation-carrier complex stability but present a maximum as a function of Ks. If the complex stability is too low, insufficient cation will be complexed at the initial interface and, similarly, if the complex stability is too high, insufficient cation will be released at the opposite interface. A compromise between thermodynamics (stability) and kinetics (exchange rates) of complexation is involved. 

To obtain theoretical expressions for E corresponding to (1), additional restrictions must be incorporated, besides those given in the preceding list. Assuming cations Iz+ and Jz + to be of the same charge z+ and the formation of any or all l n (n = 1, 2,..., N, respectively, M) cation-carrier complexes possible, the expressions given in Table 11 are obtained.33 These are based on the assumption that the concentration [cs(x)] of the uncomplexed carrier S in the liquid membrane remains constant and that... 

A final example of the use of dithiolenes comes from the work of Grimaldi and Lehn,222 and Ohki, Tagaki and Ueno.223 These groups used tetraphenylnickeldithiolene as a redox potential driven electron carrier and cation carrier through artificial membranes. Lipophilic cocarriers were employed to generate a multicomponent carrier system, in which charge equalization occurs. Applications to biomembranes, ion separation and related processes were suggested. 

The performance of calixarenes as cation carriers through H20-organic solvent H20 liquid membranes has also been studied.137 In basic metal hydroxide solutions, the monodeprotonated phenolate anions complex and transport the cations, while [18]crown-6 does not, under the same conditions. Low water solubility, neutral complex formation and potential coupling of cation transport to reverse proton flux have been cited as desirable transport features inherent in these molecules.137... 

Cryptands of type 7-9 and derivatives thereof carry alkali cations [6.4], even under conditions where natural or synthetic macrocycles are inefficient. The selec-tivities observed depend on the structure of the ligand, the nature of the cation and the type of cotransported counteranion. Designed structural changes allow the transformation of a cation receptor into a cation carrier [6.1, 6.4]. The results obtained with cryptands indicated that there was an optimal complex stability and phase-transfer equilibrium for highest transport rates. Combined with data for various other carriers and cations, they give a bell-shaped dependence of transport rates on extraction equilibrium (Fig. 11), with low rates for too small or too large... 

Electron-cation symport has been realized in a double carrier process where the coupled, parallel transport of electrons and metal cations was mediated simultaneously by an electron carrier and by a selective cation carrier [6.47]. The transport of electrons by a nickel complex in a redox gradient was the electron pump for driving the selective transport of K+ ions by a macrocyclic polyether (Fig. 12). The pro-... 

Fig. 12. Electron-cation coupled transport a redox-driven electron-cation symport consisting of an electron carrier (nickel complex) and a selective cation carrier (macrocyclic polyether). RED, potassium dithionite OX, Na3[Fe(CNft)].

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