Ethers and Cyclodextrins

Crown ethers are heterocyclic chemical compounds that, in their simplest form, are cyclic oligomers of ethylene oxide. The essential repeating unit of any simple crown ether is ethyleneoxy, i.e., —CH2CH20—, which repeats twice in dioxane and six times in 18-crown-6. Crown ethers can activate enzymes for use in organic solvents through two methods (a) direct addition of 18-crown-6 to the reaction solvent [93], or (b) co-lyophilization of the enzyme with 18-crown-6, the latter being the most effective [94, 95]. 

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Enantioresolution in capillary electrophoresis (CE) is typically achieved with the help of chiral additives dissolved in the background electrolyte. A number of low as well as high molecular weight compounds such as proteins, antibiotics, crown ethers, and cyclodextrins have already been tested and optimized. Since the mechanism of retention and resolution remains ambiguous, the selection of an additive best suited for the specific separation relies on the one-at-a-time testing of each individual compound, a tedious process at best. Obviously, the use of a mixed library of chiral additives combined with an efficient deconvolution strategy has the potential to accelerate this selection. 

Calixarenes were developed later than crown ethers and cyclodextrins but have stillbeen extensively researched. Macrocycles of calix[n]arenes are constructed by linking a number of phenol residues via methylene moieties (Fig. 2.16). Like crown ethers, the name calixarene reflects the structures of these molecules, since a calix is a chalice. Calixarenes with various cavity sizes have been designed, each of which has conformation isomers, and their phenolic hydroxyl groups are often modified. These structural characteristics allow us to create calixarene derivatives with various structural modifications. 

Mine, Y., Fukunaga, K., Itoh, K., Yoshimoto, M., Nakao, K., and Sugjmura, Y., Enhanced enzyme activity and enantioselectivity of lipases in organic solvents by crown ethers and cyclodextrins, f. Biosci. Bioeng., 95(5) 441-447, 2003. 

Functional artificial ion channels have been reported which illustrate the general criteria. The most obvious course is to prepare oligopeptides with hi helical content (S). Other reported systems are bas on cyclo xtrin (6), polymeric crown ethers (7), and "bouquet" shaped crown ether and cyclodextrin motifs (8). One of the most active systems is a simple tris-crown ether derivative repented by Gokel for the transport of sodium ions(9). All of these systems envisage a uni- or bi-molecular transmembrane structure, similar to the gramicidin structurd paradigm. 

The condensation reactions described above are unique in yet another sense. The conversion of an amine, a basic residue, to a neutral imide occurs with the simultaneous creation of a carboxylic acid nearby. In one synthetic event, an amine acts as the template and is converted into a structure that is the complement of an amine in size, shape and functionality. In this manner the triacid 15 shows high selectivity toward the parent triamine in binding experiments. Complementarity in binding is self-evident. Cyclodextrins for example, provide a hydrophobic inner surface complementary to structures such as benzenes, adamantanes and ferrocenes having appropriate shapes and sizes 12) (cf. 1). Complementary functionality has been harder to arrange in macrocycles the lone pairs of the oxygens of crown ethers and the 7t-surfaces of the cyclo-phanes are relatively inert13). Catalytically useful functionality such as carboxylic acids and their derivatives are available for the first time within these new molecular clefts. 

Lockwood SF, O Malley S, and Mosher GL. 2003. Improved aqueous solubility of crystalline astaxanthin (3,3,-dihydroxy-P,P-carotene-4,4,-dione) by Captisol (sulfobutyl ether P-cyclodextrin). Journal of Pharmaceutical Sciences 92(4) 922-926. 

A molecule that contains one or more binding sites that can accommodate inorganic or organic ions referred to as guests. The binding site could even be a cavity within a crystal structure. Although enzymes clearly qualify as examples of host molecules, the term is usually restricted to structures such as crown ethers, macrocycles, and cyclodextrins. Nevertheless, these hosts do serve as models for molecular recognition. See also Crown Ethers Macrocycles Inclusion Complexes... 

The concept of photostimulated phase separation can be applied to construct chemical-induced phase transition systems, which change the conformation reversibly in response to special chemicals. For the systems, host molecules are used as the receptor groups instead of photoisomerizable chromophores. Host molecules, such as crown ethers or cyclodextrins, are known to change the property by capturing guest chemicals in their cavity [16]. We employed benzo[l 8]crown-6 as the receptor molecule and incorporated it into the pendant groups of PNIPAM. 

Photolyses of the solid cyclodextrin complexes 1 were carried out with a Hano-via 450-W medium-pressure Hg lamp for 3 h at room temperature in a quartz vessel under vacuum. The photolysis vessel was tumbled continuously during the irradiation to ensure homogeneous photolysis of the sample. Conversions were limited to less than 20%. After photolysis, the solid complexes were dissolved in excess water and extracted with diethyl ether and chromatographed with hexane-ethyl acetate (5 1) to isolate the products in pure form. Irradiation of solid / -cy-clodextrin complexes of benzaldehyde resulted in an intramolecular reaction to give benzoin (/ )-(-)-2 and 4-benzoylbenzaldehyde 3 (7 3, 80%). 

Alkaline hydrolysis rates of a series of thiophenyl 4-X-benzoates (47 X = H, Me, N02) was significantly enhanced in the presence of cyclodextrins (CDs), and this was attributed to strong binding of the benzoyl moiety within the CD cavity and covalent catalysis by secondary hydroxy groups of the CDs (48).63 The effect of MeCN and MeOH on the alkaline hydrolysis of acetylsalicylic acid in aqueous micellar solutions was reported.64 Butylaminolysis of p-nitrophenyl acetate in chlorobenzene in the presence of different kinds of phase-transfer catalysts (crown ethers and gly-mes) supported the existence of a novel reaction pathway exhibiting a first-order dependence on the concentration of the phase-transfer catalyst and a second-order... 

The importance of non - covalent interactions in biological systems has motivated much of the current interest in supramolecular assemblies [1]. A classical example of a supermolecule has been provided by the rotaxanes [2,3], in which a molecular rotor is threaded by a threaded by a linear axle . Another examples have been previously included as cyclic crown ethers threaded by polymers, paraquat -hydroquinone complexes [4] and cyclodextrin complexes [5,6],... 

The selectivity of the Complex Formation is a very interesting subject, y - Cyclodextrin, (y - CD) has been found to form inclusion complexes with poly (methyl vinyl ether) (PMVE), poly(ethyl vinyl ether) (PEVE), and poly(n- propyl vinyl ether) (PnPVE) of various molecular weights to give stoichiometric compounds in crystalline states. However, a- cyclodextrin (a - CD) and (3 - Cyclodextrin ((3- CD) did not form complexes with poly (alkyl vinyl ether)s of any molecular weight, y -CD did not form complexes with the low molecular weight analogs, such as diethyl ether and trimethylene glycol dimethyl ether. 

On-chip chiral separation of enantiomers of adrenaline, noradrenaline, and dopamine was achieved using a mixture of carboxymethyl-p-cyclodextrin (CMCD) and a polyamidoamine dendrimer (Starburst) [120], On-chip chiral separation of enantiomers of homovanillic acid, DOPA, cDOPA, methoxy-tyramine (MT), metanephrine, and normetanephrine was achieved using a mixture of 18-crown-6-ether and carboxymethyl-P-cyclodextrin [120],... 

Based on these characteristics, cage 2 shows unique properties not demonstrated in previously known organic hosts such as crown ethers [18], cyclodextrins [19], calixarenes [20,21], calixresorcarenes [21], cucurbituril [22], and so on. The details of these properties are discussed in the following sections. 

Irradiation of tropolone alkyl ether 22 (Scheme 14) led to a 4ir-disrotatory ring closure to yield bicyclo[3.2.0]heptadienone 23 with two chiral centers, while prolonged irradiations led to the formation of a secondary product 24 [76-78]. As the same photocyclization was performed in chirally modified zeolites, it is interesting to compare the asymmetric photochemical behavior of 22 in the distinctly different chiral confined media of zeolites and cyclodextrins. Even in the... 

Kamitori S, Hirotsu K, Higuchi T (1987) Crystal and molecular structures of double macrocyclic inclusion complexes composed of cyclodextrins, crown ethers, and cations. J Am Chem Soc 109 2409- 2414... 

CE is playing a major role in the separation of chiral compounds, a field that is gaining increasing attention in pharmaceutical sciences as well as in forensic toxicology (Lurie, 1994 Novotny et al., 1994 Ward, 1994). The chirally active selectors used in CE include optically active complexes such as Cu(II)-l-histidine, Cu(II)-aspartame, cyclodextrins, modified CDs, bile salts, crown ethers, and proteins (bovine serum albumin, aracid glycoprotein, etc.). 

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