Polyethers cyclic, complexed

The strength of this bonding depends on the kind of ether Simple ethers form relatively weak complexes with metal ions but Charles J Pedersen of Du Pont discovered that cer tain polyethers form much more stable complexes with metal ions than do simple ethers Pedersen prepared a series of macrocyclic polyethers cyclic compounds contain mg four or more oxygens m a ring of 12 or more atoms He called these compounds crown ethers, because their molecular models resemble crowns Systematic nomencla ture of crown ethers is somewhat cumbersome and so Pedersen devised a shorthand description whereby the word crown is preceded by the total number of atoms m the ring and is followed by the number of oxygen atoms... 

Table 15. Log values for formation of cyclic polyether —M+ complexes in methanol and acetonitrile. T — 250 (20)...

The 18-crown-6-cyclic polyether-KBr complex catalyses the homogeneous liquid phase molecular oxygen oxidation of ethylbenzene to the hydroperoxide. The macrobicyclic ligands (cryptands) are strong bases but the rates of proton transfer from ethyl nitroacetate to the free base cryptand and to the mono-protonated cryptand are ca, 10 and 100-fold smaller, respectively, than that of transfer to a normal base of similar basicity. This is attributed either to steric hindrance to proton transfer or to proton transfer occurring only to the thermodynamically unfavourable exo-nitrogen conformation. However, a large kinetic isotope effect = 3.9) is observed for the protonation of cryptand... 

The structures of cyclic polyether-cation complexes postulated by Pedersen,and later confirmed by X-ray studies do not require removal of the entire solvation shell, because coplanar complexing of the cation with a polyether still allows solvent contacts perpendicular to the plane of the ring. Perpendicular solvent contact was noted experimentally when X-ray studies of the sodium dibenzo-18-crown-6 complex revealed two molecules of water complex-ed above and below the plane of the polyether ring. These results were noteworthy, because the complex had been prepared in methanol, and no water had been deliberately added to the crystallizing solvent, indicating the preference of the cation to bind to water rather than to methanol. 

Since 1950 a number of polyether antibiotics have been discovered using fermentation technol ogy They are characterized by the presence of sev eral cyclic ether structural units as illustrated for the case of monensm in Figure 16 3a Monensin and other naturally occurring polyethers are similar to crown ethers in their ability to form stable complexes... 

Ethers form Lewis acid Lewis base complexes with metal ions Certain cyclic polyethers called crown ethers, are particularly effective m coor dinatmg with Na" and K" and salts of these cations can be dissolved m nonpolar solvents when crown ethers are present Under these conditions the rates of many reactions that involve anions are accelerated... 

Critical micelle concentration (Section 19 5) Concentration above which substances such as salts of fatty acids aggre gate to form micelles in aqueous solution Crown ether (Section 16 4) A cyclic polyether that via lon-dipole attractive forces forms stable complexes with metal 10ns Such complexes along with their accompany mg anion are soluble in nonpolar solvents C terminus (Section 27 7) The amino acid at the end of a pep tide or protein chain that has its carboxyl group intact—that IS in which the carboxyl group is not part of a peptide bond Cumulated diene (Section 10 5) Diene of the type C=C=C in which a single carbon atom participates in double bonds with two others... 

Cram has published several studies indicating that complexation of ammonium salts was greatly enhanced by using cyclic polyethers over the corresponding acyclic ones. These molecules were analogs of the binaphthyl systems under study and were generally prepared by phenoxide substitution on the appropriate tosylate. The approach is illustrated below in Eq. (7.9). ... 

Crown ether (Section 16.4) A cyclic polyether that, via ion-dipole attractive forces, forms stable complexes with metal ions. Such complexes, along with their accompanying anion, are soluble in nonpolar solvents. 

Cholanic acid also possesses the ability of transporting cations across a lipophilic membrane but the selectivity is not observed because it contains no recognition sites for specific cations. In the basic region, monensin forms a lipophilic complex with Na+, which is the counter ion of the carboxylate, by taking a pseudo-cyclic structure based on the effective coordination of the polyether moiety. The lipophilic complex taken up in the liquid membrane is transferred to the active region by diffusion. In the acidic region, the sodium cation is released by the neutralization reaction. The cycle is completed by the reverse transport of the free carboxylic ionophore. 

Markies et al. have studied the coordination of zinc to cyclic and acyclic polyether ligands. In some cases the zinc is not coordinated within the ligand cavity but only through two of the ether donors in the macrocyclic ring.360 The bis(methoxyethyl)ether complex of zinc diphenyl (41) is five-coordinate with three ether oxygens coordinating from the acyclic ligand.361... 

The second ligand type consists of a large group of cyclic compounds incorporating numbers of ether functions as donors. Structure (22) illustrates a typical example. Such crown polyethers usually show strong complexing ability towards alkali and alkaline earth ions but their tendency to coordinate to transition metal ions is less than for the above... 

The macrocycle types discussed so far tend to form very stable complexes with transition metal ions and, as mentioned previously, have properties which often resemble those of the naturally occurring porphyrins and corrins. The complexation behaviour of these macrocycles contrasts in a number of ways with that of the second major category of cyclic ligands - the crown polyethers. 

Crown polyethers. Macrocyclic effects involving complexes of crown polyethers have been well-recognized. As for the all-sulfur donor systems, the study of the macrocyclic effect tends to be more straightforward for complexes of cyclic polyethers especially when simple alkali and alkaline earth cations are involved (Haymore, Lamb, Izatt Christensen, 1982). The advantages include (i) the cyclic polyethers are weak, uncharged bases and metal complexation is not pH dependent (ii) these ligands readily form complexes with the alkali and alkaline earth cations... 

The crowns as model carriers. Many studies involving crown ethers and related ligands have been performed which mimic the ion-transport behaviour of the natural antibiotic carriers (Lamb, Izatt Christensen, 1981). This is not surprising, since clearly the alkali metal chemistry of the cyclic antibiotic molecules parallels in many respects that of the crown ethers towards these metals. As discussed in Chapter 4, complexation of an ion such as sodium or potassium with a crown polyether results in an increase in its lipophilicity (and a concomitant increase in its solubility in non-polar organic solvents). However, even though a ring such as 18-crown-6 binds potassium selectively, this crown is expected to be a less effective ionophore for potassium than the natural systems since the two sides of the crown complex are not as well-protected from the hydro-phobic environment existing in the membrane. 

Macrocyclic compounds with ion-chelating properties occur naturally and often function as ionophores, translocating ions across biological membranes many of these compounds are small cyclic polypeptides. Some natural carboxylic polyethers are selective for Li+ and are, therefore, ionophores for Li+. Monensin, shown in Figure Id, is a natural ionophore for Na+ but it will also complex with Li+ and it has been shown to mediate the transport of Li+ across phospholipid bilayers [21]. It has been proposed that synthetic Li+-specific ionophores have a potential role as adjuvants in lithium therapy, the aim being to reduce the amount of... 

Electrodes based on solutions of cyclic polyethers in hydrocarbons show a selective response to alkali metal cations. The cyclic structure and physical dimensions of these compounds enable them to surround and replace the hydration shell of the cations and carry them into the membrane phase. Conduction occurs by diffusion of these charged complexes, which constitute a space charge within the membrane. Electrodes with a high selectivity for potassium over sodium (> 1000 1) have been produced. 

Tandem carbonyl olefmation—olefm metathesis utilizing the Tebbe reagent or dimethyl-titanocene is employed for the direct conversion of olefmic esters to six- and seven-mem-bered cyclic enol ethers. Titanocene-methylidene initially reacts with the ester carbonyl of 11 to form the vinyl ether 12. The ensuing productive olefm metathesis between titano-cene methylidene and the cis-1,2 -disubstituted double bond in the same molecule produces the alkylidene-titanocene 13. Ring-closing olefin metathesis (RCM) of the latter affords the cyclic vinyl ether 14 (Scheme 14.8) [18]. This sequence of reactions is useful for the construction of the complex cyclic polyether frameworks of maitotoxin [19]. 

Crown ethers are cyclic polyethers designated [n]crown-m where n is the ring size and m the number of oxygen atoms, for instance [18] crown-6 1. They show a high affinity for cationic guest molecules, especially alkali metal cations, where the cation is commonly complexed within the cavity of macrocycle or sand-... 

The formation of complexes of 2 1 stoichiometry is not restricted to cyclic ligands it has also been observed with linear polyethers (Kodama and Kimura, 1976 Tiimmler et al., 1977). 

Similar complexes with non-cyclic polyethers that could not be obtained by Pedersen were recently described by Rasshofer and Vogtle (1978) and Suh and Saenger (1978). 

As cyclic polyethers (polyethylene oxides), some of this group of aprotic complexing solvents may be subject to peroxidation, though no reports have been so far noted. 

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