Ionophores, cation binding

Figure 5 also shows the effect of the ionophore concentration of the Langmuir type binding isotherm. The slope of the isotherm fora membrane with 10 mM of ionophore 1 was roughly three times larger than that with 30 mM of the same ionophore. The binding constant, K, which is inversely proportional to the slope [Eq. (3)], was estimated to be 4.2 and 11.5M for the membranes with 10 mM and 30 mM ionophore 1, respectively. This result supports the validity of the present Langmuir analysis because the binding constant, K, should reflect the availability of the surface sites, the number of which should be proportional to the ionophore concentration, if the ionophore is not surface active itself In addition, the intercept of the isotherm for a membrane with 10 mM of ionophore 1 was nearly equal to that of a membrane with 30 mM ionophore 1 (see Fig. 5). This suggests the formation of a closest-packed surface molecular layer of the SHG active Li -ionophore 1 cation complex, whose surface concentration is nearly equal at both ionophore concentrations. On the other hand, a totally different intercept and very small slope of the isotherm was obtained for a membrane containing only 3 mM of ionophore 1. This indicates an incomplete formation of the closest-packed surface layer of the cation complexes due to a lack of free ionophores at the membrane surface, leading to a kinetic limitation. In this case, the potentiometric response of the membrane toward Li+ was also found to be very weak vide infra).

We first discuss the thermodynamics of cation binding by ionophores where only a couple of weak interactions are mainly involved and the binding behavior seems relatively simple to analyze. 

In view of the compensatory enthalpy-entropy relationship observed for a wide variety of ionophore types, we may conclude that the cation-binding behavior, where the weak ion-dipole and dipole-dipole interaction is the major driving force for complexation, can be quantitatively analyzed and characterized by the slope and intercept of the AH-TAS plot without any exception. In this context, it is stimulating to extend the scope of this theory to the inclusion complexation of organic guests with molecular hosts. 

The question of carrier design was first addressed for the transport of inorganic cations. In fact, selective alkali cation transport was one of the initial objectives of our work on cryptates [1.26a, 6.4]. Natural acyclic and macrocyclic ligands (such as monensin, valinomycin, enniatin, nonactin, etc.) were found early on to act as selective ion carriers, ionophores and have been extensively studied, in particular in view of their antibiotic properties [1.21, 6.5]. The discovery of the cation binding properties of crown ethers and of cryptates led to active investigations of the ionophoretic properties of these synthetic compounds [2.3c, 6.1,6.2,6.4-6.13], The first step resides in the ability of these substances to lipophilize cations by complexation and to extract them into an organic or membrane phase [6.14, 6.15]. 

Examples such as this show the importance of alkali metal cation binding and transport in biochemistry, and a great deal of effort has been expended in supramolecular chemistry in attempts to understand natural cation binding and transport of the ionophore and channel type and to develop artificial systems capable of similar selectivities and reactivities. We will take a close look at many of these compounds in Chapter 3. 

We have already seen in Section 2.2 how the transport of both anions and cations is a vital part of biochemistry. We will examine supramolecular models of biological ion channels in detail in Chapter 12 but here we focus on some simple ion transport systems (ionophores) relevant to simultaneous anion and cation binding. Because of the need to maintain overall and local charge neutrality during any transport process the transport of individual ions across a biological or artificial membrane never occurs in isolation. There are two kinds of primary transport processes. Ion exchange or antiport, occurs when chemically different ions of like charge such as Na+ and K+ are simultaneously transported in... 

The structures of synthetic pyran-based ionophores have been investigated. m-2-Alkyl-3-oxytetrahydropyrans form useful subunits for the preparation of new types of ionophores with C2 symmetry <2005T8177>. X-Ray crystallography of some of these compounds provided useful information on solid-state conformational preferences that can be related to the cation-complexation properties in solution. In a related study, the synthesis of 18-32-membered cyclic pyran-based compounds of the type shown (50 and 51) was described <1996TL343, 1995JA12649>. Studies of these compounds focused on structural elements important for control of the shape and cation-binding ability and the structures of several of the compounds were determined by X-ray crystallography. 

Important cation binding systems in Nature are, for example, a class of macro-cyclic compounds termed ionophores and proteins that bind quaternary ammonium ions such as acetylcholine. The ionophores valinomycin 1, nonactin, the ennia-tines, and baeuvericin are cation binders that are structurally quite diverse, yet... 

Fig. 3 A self-assembling ionophore. Formation of a Ni(II)-salicylaldimine complex preorganizes a crown ether-like cation binding site...

Both in their general pattern of structure and mode of cation binding, 222 and 223, as well as many other naturally occurring ionophores, are similar to crown... 

Lu HJ, Pan YT, Wu YJ, and Yin MC. Tripodal lipophilic ionophores Synthesis, cation binding and transport through liquid... 

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