Cation binding

Shortly after the original crown ether work, Jean-Marie Lehn realised that donor atoms can be situated within a three-dimensional array to completely encapsulate the ion from the outside medium. Lehn and co-workers prepared a range of bicyclic systems named cryptands, one of the first of which was [2.2.2]cryptand (2.13). Each cryptand is denoted by the number of heteroatoms that are incorporated in the bridges linking between the bridgehead atoms (normally nitrogen atoms). Therefore, [2.1.1]cryptand, [2.2.1]cryptand and [2.2.2]cryptand contain four, five and six oxygen atoms, respectively (2.11-2.13). 

In 1987, Pedersen and Lehn shared the Nobel Prize for the development of Supramolecular Chemistry with a third recipient, Donald Cram, also very well-known for his work in carbanion chemistry. Cram realised that the chemical reactivity of a carbanion could be increased by the separation of a counter-cation from its anion. This separation was achieved by fully encapsulating the cation with cyclic polyethers and represents an example of the naked anion effect. This is where the anion has been stripped away from its counter-ion, such that there is little or no association between the anion and cation. Cram and his team went about synthesising cyclic polyethers in which the oxygen atoms comprise a small cavity that is rigidly preorganised in an octahedral array. These macrocycles are termed spherands, of which the Li -selective spherand-6 (2.15) is one of the best-known examples. 

Since the work of Pedersen, Lehn and Cram, an enormous amount of research has been conducted using macrocycles for binding cation, anion and neutral species, sensing and catalysis, as well as the synthesis of self-assembled rotaxanes, catenanes and knots (see Chapter 3). Subsequent sections give a brief overview of some of the most important classes of compound. 

It was initially proposed that there is an optimal spatial fit between crown ethers and particular cations. It is true that [18]crown-6 is selective for K, whereas the larger [21]crown-7 has a higher affinity for Rb and Cs than K. However, modem understanding of these systems has somewhat modified this simple size-fit idea, particularly because of the flexibility of the crown ethers - their size is not a constant. Table 2.1 shows the binding constants obtained for a selection of cations with various crown ethers. 

If the cation is exchanged for an ammonium ion instead of an alkali-metal, the complex stability drastically increases in favour of the lariat ether over the 

FIGURE 9.15 Schematic representation of structural models of Pb(ll) adsorption onto goe-thite surfaces, (a) Inner-sphere surface complex (b) surface polymerization anchored by some inner-sphere bound Pb(II) ions. (Reprinted with permission from Roe et al. 1991, 367—373. Copyright 1991 American Chemical Society.) 

Zn adsorption onto silica and gibbsite was also studied by XAS methods here EXAFS spectroscopy was employed to observe both the sorbed Zn environment and the kinetics of the process (Roberts, Ford, and Sparks 2003). In the case of silica, EXAFS revealed that Zn was in octahedral coordination with first-shell 

Other X-ray spectroscopic studies include cadmium adsorption on aluminum oxides (Papelis et al. 1995), where it was found that Cd-O distances and coordination numbers (6 oxygens) on two aluminas agree with Cd-O distances and coordination in aqueous solutions. In low sorption density samples, absence of cadmium 

FIGURE 9.17 Calculated Zn(II)-Ti02 surface complexes from density functional theory (a) dissolved Zn(II) with six outer-sphere water molecules (b) monodentate mononuclear (c) bidentate binuclear (BB) (d) bidentate mononuclear (BM). Gray, black, large white, and small white circles denote Zn, O, Ti, and H atoms, respectively. (Reprinted with permission from He et al. 2011, 1873-1879. Copyright 2011 American Chemical Society.) 

Of special importance is the adsorption of radionuclides onto soil components. The adsorption of Np(V) onto goethite has been studied by Combes et al. (Combes et al. 1992), finding that sorbed Np(V) is present as a mononuclear species similar to that of dissolved NpO J in water. The results do not rule out the possibility that the surface 

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Y. Inoue and G. W. Gokel, eds.. Cation Binding by Macroycles, Marcel Dekker, New York, 1990. 

Almost as soon as Pedersen announced his discovery of the crown ethers (see Chaps. 2 and 3) it was recognized by many that these species were similar to those prepared by Busch and coworkers for binding coinage and transition metals (see Sect. 2.1). The latter compounds contained all or a predominance of nitrogen and sulfur (see also Chap. 6) in accordance with their intended use. The crown ethers and the polyazamacrocycles represented two extremes in cation binding ability and preparation of the intermediate compounds quickly ensued. In the conceptual sense, monoazacrowns are the simplest variants of the macrocyclic polyethers and these will be discussed first. 

A detailed spectral analysis was undertaken and mechanical properties are described, but no information is reported on the cation binding abilities of the various species thus produced . 

Such a structure might well exhibit significant cation binding but this possibility does not appear to have been investigated. 

Although the first all-sulfur macrocycles were prepared many years ago " the first systematic study of such compounds was initiated by Busch and his coworkers , who were interested in the cation binding properties of such ligands. A sequential synthesis was utilized to produce 1,4,8,11-tetrathiacyclotetradecane [tetrathia-14-crown-4 (70)] . In the first step, 1,3-propanedithiol is metallated using sodium and alkylated with 2-chloroethanol. The diol was then treated with thiourea to form the dimercapto-dithioether compound 9. The latter was once again metallated with sodium and allowed to react with 1,3-dibromopropane. The yield of 70 in the ring closure step, conducted at high dilution in absolute ethanol, was 7.5% after recrystallization. The entire sequence is illustrated in Eq. (6.8) . ... 

A good deal of work has been done on polymeric crown ethers during the last decade. Hogen Esch and Smid have been major contributors from the point of view of cation binding properties, and Blasius and coworkers have been especially interested in the cation selectivity of such species. Montanari and coworkers have developed a number of polymer-anchored crowns for use as phase transfer catalysts. Manecke and Storck have recently published a review titled Polymeric Catalysts , which may be useful to the reader in gaining additional perspective. 

In the early work, benzene formed the basis of a variety of multi-armed structures. Analogs bearing from 2—6 arms were prepared and compared for cation binding ability. The only indication of mode of synthesis for the hexa-substituted benzene derivative is that it was obtained on reaction of benzene-hexakis(methanethiol) and l-bromo-3,6,9-trioxatridecane . The reaction is illustrated in Eq. (7.6), below, devoid of reaction conditions and yields which were not specified. 

The bulk of the work which has been performed on open-chained crown ether and cryptand equivalents, especially for application to general cation binding studies has been accomplished by Vogtle and his coworkers. Vogtle has reviewed both his own and other work in this field . 

In other sections in this chapter, we have referred to a variety of macropolycyclic structures which are more elaborate than the simple three-stranded bicyclic cryptands. This includes bridged double-macrocycles " , in-out bicyclic amines and the macrotricyclic quaternary ammonium salts of Schmidtchen. In addition to these, there are two other types of compounds which deserve special note. The first of these is a stacked twin-ring cryptand, but it is a hybrid molecule rather than a double-cryptand . The species shown below as 20 is a crowned porphyrin, and was designed to provide a pair of metal cation binding sites similar to those which might be available in natural biological systems . 

K-K Complexation Hydrogen bonding Inclusion Dipole stacking Steric interactions Anionic or cationic binding... 

In addition to [18]aneN6, a newly synthesized [18]aneN6-hexaacetic acid (X) has also been tested 34,35). (X) was originally designed to combine the anion-binding function of [18]aneN6 with the cation-binding function of EDTA for more efficient dissolution of calculi. 

Spatial variation in pectin structure and cation binding... 

To understand the Na,K-pump mechanism it is obviously important to identify the cation pathway and the sites for binding and occlusion of Na and K relative to the intramembrane portion of the protein. The groups coordinating the cations should be identified and it should be known if the pump has independent sites for Na" and K" " or if the cations bind alternately to the same set of sites. With a stoichiometry of 3Na /2K per ATP split this would mean that two sites bind Na and alternately, while one site only binds Na". ... 

It has been established by substitution of for Mg that, prior to phosphorylation, the divalent cation binds at a cytosolic site with a stoichiometry of about 1 mol per phosphorylation site [124,125]. These experiments also demonstrated that the phosphorylation rate is sensitive to the nature of the divalent cation bound. With Mg bound, the phosphorylation rate is about 20 times faster than with Ca bound. The divalent cation dissociates after dephosphorylation, suggesting that it is tightly bound to the phosphoenzyme during the reaction cycle. It was also demonstrated that the type of divalent cation that occupies the divalent cation site required for phosphorylation is important for the step 2K E2-P to 2K E2 P to 2K E2 [124,125]. With Mg bound, the 2K E2-P conformer is -sensitive, whereas with Ca bound, the intermediate is -insensitive. 

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