Dissociation ionophores

It was found in later work that it is precisely the idea of ionic hydration that is able to explain the physical nature of electrolytic dissociation. The energy of interaction between the solvent molecules and the ions that are formed is high enough to break up the lattices of ionophors or the chemical bonds in ionogens (for more details, see Section 7.2). The significance of ionic hydration for the dissociation of electrolytes had first been pointed out by Ivan A. Kablukov in 1891. 

At the beginning of the twentieth century the idea was put forward that in solutions of strong electrolytes the degree of dissociation is not simply high but dissociation of the solute is complete (i.e., equilibrium between ions and undissociated molecules does not exist). This point is particularly evident for ionophors, which in the solid state do not possess individual molecules and for which it is unlikely that undissociated molecules should appear in a solution. 

There appear to be two major ways by which ionophores aid ions to cross membrane barriers. Ionophores such as valinomycin and nonactin enclose the cation such that the outside of the complex is quite hydro-phobic (and thus lipid-soluble). The transport behaviour thus involves binding of the cation at the membrane surface by the antibiotic, followed by diffusion of the complexed cation across the membrane to the opposite surface where it is released. Such carrier type ionophores can be very efficient, with one molecule facilitating the passage of thousands of ions per second. A prerequisite for efficient transport by this type of ionophore is that both the kinetics of complex formation and dissociation be fast. 

Li+ required for efficacy by increasing its bioavailability and possibly to reduce some of the unpleasant side effects sometimes experienced with this drug. The toxicity of such ionophores and kinetics of ion complexa-tion, both association and dissociation, are obviously important factors under consideration in this field of research. 

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. 

In the above sections, we considered electrolytes that are ionophores.10 Iono-phores, like sodium chloride, are ionic in the crystalline state and are expected to dissociate into free ions in dilute solutions. In fact, in high-permittivity solvents (er>40), ionophores dissociate almost completely into ions unless the solutions are of high concentration. When an ionophore is completely dissociated in the solution, its molar conductivity A decreases linearly with the square root of the concentration c (<10 2 M) ... 

Valinomycin is one of a group of compounds termed ionophores, which facilitate movement of ions across phospholipid membranes. Valinomycin has the cyclic structure f-t>valine-lactate-L-valine-hydroxy valerate-] 3. This figure shows the structure of the complex formed between valinomycin and K+. The complex is soluble in organic solvents and can pass through the phospholipid bilayer of the mitochondrial inner membrane. K+ dissociates reversibly from the complex in the aqueous solution on either side of the membrane. 

Nocobactin NA is the generic name given to a series of compounds obtained after dissociation of a ferric complex isolated from the bacterium Nocardia as-teroides grown under iron-deficient conditions (97). Spectroscopic, degradative, and partial synthetic studies led to the formulation 187 for the compounds. The nocobactins are lipid-soluble ionophores whose function appears to be the transport of iron across the lipid-rich cell boundary of the producing organism. 

The difficulty in explaining the effects of inorganic solutes on the physical properties of solutions led in 1884 to Arrhenius theory of incomplete and complete dissociation of ionic solutes (electrolytes, ionophores) into cations and anions in solution, which was only very reluctantly accepted by his contemporaries. Arrhenius derived his dissociation theory from comparison of the results obtained by measurements of electroconductivity and osmotic pressure of dilute electrolyte solutions [6]. 

Solutions of non-electrolytes contain neutral molecules or atoms and are nonconductors. Solutions of electrolytes are good conductors due to the presence of anions and cations. The study of electrolytic solutions has shown that electrolytes may be divided into two classes ionophores and ionogens [134]. lonophores (like alkali halides) are ionic in the crystalline state and they exist only as ions in the fused state as well as in dilute solutions. Ionogens (like hydrogen halides) are substances with molecular crystal lattices which form ions in solution only if a suitable reaction occurs with the solvent. Therefore, according to Eq. (2-13), a clear distinction must be made between the ionization step, which produces ion pairs by heterolysis of a covalent bond in ionogens, and the dissociation process, which produces free ions from associated ions [137, 397, 398]. 

The nucleophilic reactivity of an anion depends not only on the extent of its specific solvation, but also on the degree of association with the corresponding cation. An ion-pair associated anion (or cation) is much less reactive than a free, non-associated ion. As early as 1912, Acree postulated that the reactivity of an anionic nucleophile should be depressed when its salt is incompletely dissociated [332]. Due to incomplete dissociation of the ionophore, the reaction rate constant will fall as its concentration increases. The simple model given in Eq. (5-124) is consistent with the observation that in aU cases ion association deactivates the nucleophile [289],... 

Rosatzin et al. copolymerised V,W-dimethyl-V,V -bis(4-vinylphenyl)-3-oxapen-tanediamide (a metal ionophore), divinylbenzene and styrene in a chloroform solution in the presence of Ca(ll) or Mg(II) [10]. The Ca(II) ionophore resin is illustrated in Scheme 9.4. The metal ion added to the matrix mixture, was expected to act as a template for the ionophore during the polymerisation. The resulting polymers were analysed for their ability to extract ions from aqueous methanol. The polymers prepared against Ca(II) and Mg(II) were found to bind Ca(II) with 6- and 1.7-times lower dissociation constants, respectively, when... 

It is important to note that ionophores are not always completely dissociated. For example, when NaCl is dissolved in a solvent of lower relative permittivity, such as methanol, it is ion paired to some extent. The thermodynamics of systems with ion pairing is considered separately in section 3.10. Under these circumstances the ionophore behaves in the same way as a weak electrolyte. On the other hand, all ionogenes are not weak electrolytes. For example, HCl, which is a molecule in the gas phase, is completely dissociated in water and therefore is a strong electrolyte. Acetic acid is completely dissociated in liquid ammonia, which is a much stronger base than water. Thus, the solvent plays an important role in determining the extent of electrolyte dissociation in solution. In the following discussion the traditional terms, strong and weak electrolytes, are used. 

Many problems still remain to be solved for pH FOCS. Areas still not completely under control are the techniques of immobilization and grafting on the support, permanent monitoring of the concentration of the indicators, ionophore lifetime [60], stability of maintenance of the dye on the support over a wide pH range, determination of the dissociation constant of the immobilization dye [61], optode reversibility, reproducibility of their manufacture (disposal optodes), monitoring of the influence of the medium, and the simplification of calibration procedures. Some progress has been achieved in the understanding of the influence of the ionic strength of the medium. 

According to Katano and Senda [15,16], the transfer of Pb ions in the presence of citrate in W facilitated by 1,4,7,10,13,16-hexathiacyclo-octadecane is limited by the dissociation reaction of Pb + ions from their complexes with citrate in W, while the transfer of Pb ions across the interface and the complex formation of Pb ions with the ionophore in O are fast. The quantitative analyses of linear-sweep voltammograms and normal-pulse polarograms consistently show that the entire process is described by a CE mechanism and that the dissociation and association rate constants of the Pb -citrate complex are... 

Volmer DA, Lock CM, Electrospray ionization and collision-induced dissociation of antibiotic polyether ionophores. Rapid Commun. Mass Spectrom. 1998 12(4) 157-164. 

The rapid calcium efflux efficiently decreases luminal calcium concentration, which induced acceleration of Ca -pump activity due to facilitation of calcium dissociation from a low affinity calcium-binding site (luminal site). To investigate the possible involvement of luminal calcium in the Ca pump stimulation, the luminal Ca concentration was indirectly manipulated by a Ca -ionophore and a calcium chelator (Figure 5). A23187 induced a five-fold increase in Ca pump activity [3] due to an increase of calcium permeability. Under this condition, Ca pump stimulation by flubendiamide was mostly eliminated [3], suggesting the involvement of luminal Ca in the Ca pump stimulation by flubendiamide. 

Generally, two different modes of transmembraneous transport have been established the carrier and the channel mechanism. The ionophores considered here act by the carrier mechanism. They form discrete antibiotic cation complexes at one interface of the membrane which then migrate across the membrane to the other interface where the metal ion is released. This kind of transport is displayed by the depsipeptide-type antibiotics which form positively charged complexes with metal ions. This is also true for the macrotetrolide nactins whereas the open-chain polyether antibiotics of the nigericin family mainly lead to electrically neutral metal ion complexes by dissociation of their carboxyl group. For the latter type of carriers, the ion transport of metal ions is coupled with a transfer of protons in the opposite direction. 

Ionophores are substances that already exist as ionic crystals in their pure state, such as alkali metal halides. When dissolved in a solvent, ionophores are initially completely dissociated in the solution and their ions are solvated. However, association to ion pairs and higher ion aggregates with and without inclusion of solvent molecules may occur in many solvents depending on electrolyte concentration and solvent permittivity. Equation (1) shows the ionic species in an aqueous CdS04 solution—solvated ions and ion pairs—which can be detected by appropriate methods and which determine the physical properties of this solution ... 

Functional ISEs based on charged carriers can be fabricated with membranes that contain just the salt of a charged ionophore, since the ionophore has both ionophoric and ion-exchanger properties. However, it has been shown that the corresponding sensing selectivities are then often less than ideal [40]. Consider, for example, a membrane with a charged ionophore selective for a monovalent anion. The concentration of uncomplexed ionophore in the membrane is ordinarily small and dictated by the dissociation constant of the complex ... 

---