Selectivity with cyclodextrins

Immobilization. The abiUty of cyclodextrins to form inclusion complexes selectively with a wide variety of guest molecules or ions is well known (1,2) (see INCLUSION COMPOUNDS). Cyclodextrins immobilized on appropriate supports are used in high performance Hquid chromatography (hplc) to separate optical isomers. Immobilization of cyclodextrin on a soHd support offers several advantages over use as a mobile-phase modifier. For example, as a mobile-phase additive, P-cyclodextrin has a relatively low solubiUty. The cost of y- or a-cyclodextrin is high. Furthermore, when employed in thin-layer chromatography (tic) and hplc, cyclodextrin mobile phases usually produce relatively poor efficiencies. 

Figure 3.7 [continued) (b) Chromatograms of (iii) the dichloromethane extract of strawberry fruit yoghurt analysed with an apolar primary column, with the heart-cut regions indicated, and (iv) a non-racemic mixture of y-deca-(Cio) and 7-dodeca-Cj2 lactones isolated by heart-cut transfer, and separated by using a chiral selective modified cyclodextrin column. Reproduced from A. Mosandl, et al J. High Resol. Chromatogr. 1989, 12, 532 (39f. 

The well-known reaction between phenol and chloroform in the presence of concentrated sodium hydroxide is amenable to dramatic changes with cyclodextrins. -cyclodextrin, immobilized with epichlorohydrin, seems to give 100 % selectivity for para... 

In a similar fashion, steroids are molecules that have been investigated by disruption of FRET. The sensor is a double labeled peptide with cyclodextrin bound to one side chain. The latter keeps the fluorophores closely together by accommodating the coumarin into its cavity thereby ensuring efficient FRET. Steroids compete for the cavity of cyclodextrin and displace the coumarin reducing FRET efficiency. This model, although useful for in vitro applications, seems to be poorly selective for its application in biological samples [95],... 

Rawjee, Y.Y., Stark, D.U., Vigh, G. Capillary electrophoretic chiral separations with cyclodextrin additives I. acids Chiral selectivity as a function of pH and the concentration of P-cyclodextrin for fenoprofen and ibuprofen. J. Chromatogr. 1993, 635, 291-306. 

Extensive comparisons between GC and SFC have been reported in chiral separation [63-66]. Zoltan investigated the performance of SFC and GC using the same chiral capillary columns coated with cyclodextrin-based stationary phases. It was observed that chiral selectivity was higher in GC than in SFC using the same open tubular column at the identical temperature (e.g., >100°C). However, the selectivity in SFC was significantly increased at low temperatures, especially for polar compounds [67]. 

It was pointed ouF that while ionomer-modified electrodes have greater selectivity than naked electrodes, ionomers provide only a general form of selectivity (charge type and mass or hydrophobicity selectivity), and special methods were suggested to improve specific selectivity. For example, it was thought that applying an additional cellulose acetate layer over the Nafion film would make the electrode selective with respect to dopamine specifically (in contrast to other neurotransmitters). To make the electrode system specifically selective to o-nitrophenol (in contrast to /(-isomer), a complexation with cyclodextrin was performed, which increased the selectivity ratio one order of magnitude with respect to the o-isomer. ... 

F Lelievre, P Gareil, A Jardy. Selectivity in capillary electrophoresis application to chiral separations with cyclodextrins. Anal Chem 69 385—392, 1997. 

A real breakthrough in this field occurred when enantio-cGC became more and more available. In particular, since 1988 selectively modified cyclodextrins have been synthesised, serving as chiral stationary phases in enantio-cGC, reported by Schurig and Novotny [I], Konig et al. [2, 3], Armstrong et al. [4], Dietrich et al. [5,6 ], Saturin et al. [7], and Bicchi et al. [8]. 6-O-silylated modified /I-cyclo dextrin and y-cyclodextrin derivatives of well-defined structure and purity were synthesised and have proved to be chiral stationary phases of unique selectivity and versatility and, therefore, are successfully used in simultaneous enantio-cGC analysis [5,6]. Further derivatives were recently reported by Taka-hisa and Engel [9, 10], dealing with 2,3-di-0-methoxymethyl-6-0-tert-butyldi-methylsilyl modified cyclodextrins as chiral stationary phases in enantio-cGG. 

Permethylation of CD hydroxyl groups markedly changes the chromatographic selectivity in comparison to native CDs. Various CD derivatives are described. The various moieties used to functionalize the CDs greatly affect the enantioselectivity. Since the pioneering work of Armstrong, the topic of separations with cyclodextrins or cyclodextrin derivatives has been well documented (44). 

Crown ethers are attractive platforms from which membrane-spanning substituents can be appended but suffer from a lack of rigidity. It can be argued that cyclic compounds with well-defined central cavities should be more robust and selective. The cyclodextrins and calixarenes have both been employed in ion channel mimetic compounds. These compounds can have different functional groups at their... 

The situation is complex. In another study we examined the cyclization of compound 54 catalyzed by cyclodextrin bis-imidazoles [140]. This dialdehyde can perform the intramolecular aldol reaction using the enol of either aldehyde to add to the other aldehyde, forming either 55 or 56. In solution with simple buffer catalysis both compounds are formed almost randomly, but with the A,B isomer 46 of the bis-imidazole cyclodextrin there was a 97 % preference for product 56. This is consistent with the previous findings that the catalyst promotes enolization near the bound phenyl ring, but in this case the cyclization is most selective with the A,B isomer 46, not the A,D that we saw previously. Again the enolization is reversible, and the selectivity reflects the addition of an enol to an aldehyde group. The predominant product is a mixture of two stereoisomers, 56A and 56B. Both were formed, and were racemic despite the chirality of the cyclodextrin ring. 

Metalloporphyrins can catalyze the hydroxylations of solvent species such as cyclohexane. From our studies with cyclodextrin dimers, we concluded that by attaching cyclodextrin rings to metalloporphyrins we should be able to bind substrates in water and achieve selective hydroxylations directed by the geometries of the complexes. This was successful. 

Microsolvent effects in the cyclodextrin cavity have also been observed in hypochlorite chlorination of acetophenone1029. Higher para selectivity has been observed in the bromination of acetanilide and benzanilide in presence of cyclodextrins or amylose1030 and in the anodic chlorination of anisole with cyclodextrin-modified electrode1031. 

Cholesterol may be removed selectively by cyclodextrins. Melted milk fat is mixed with a cyclodextrin solutions and the complex is removed by washing. The ability of cyclodextrin to form an inclusion complex with cholesterol has been applied to reduce the cholesterol content of milk fat, cream or milk (Courregelongue and Maffrand, 1989 Oakenfull et al., 1991). However, the high cost of cyclodextrin prevents its use on an industrial scale. 

Figure 6 shows the complete separation of five amino acids (lysine, alanine, phenylalanine, tyrosine and tryptophan) on a column packed with cyclodextrin polymers (58). The best separation of these amino acids was obtained on the column packed with 0-cyclo-dextrin polymer. On the other hand, tryptophan could be separated on a-cyclodextrin polymer column with the best selectivity. Also, fifteen additional non-aromatic natural a-amino acids were chromatographed on p-cyclodextrin polymer, but their peaks appeared either between, or together with, those of alanine and lysine. 

On the other hand, capillary gas chromatography with liquid crystals yields very good analytical separations (even for critical pairs of isomers) as the GLC system is used and an inherent lower selectivity compared to cyclodextrins is compensated for by the higher efficiency of the capillary columns Therefore, future work should be directed toward reproducible preparation of capillary columns with cyclodextrins and to other liquid crystals with a higher selectivity ... 

Feng L, Chen Z, Wang D (2007) Selective sensing of Fe3 + based on fluorescence quenching by 2, 6-bis(benzoxazolyl)pyridine with ) -cyclodextrin in neutral aqueous solution. Spectrochimica Acta A 66 599-603... 

Although this work does not focus on the host properties of dendrimers, it is interesting to mention briefly some work that has been done on the covalent functionalization of cyclodextrins with dendritic structures, to yield what can be appropriately described as dendritic cyclodextrins. Early work on this area was reported by Ahern et al. [18], which prepared P-CD derivatives per-functionalized with hydroxyethylamino chains on the 6-deoxy position (primary face). These CDs, considered as dendrimer precursors, showed a modest degree of binding selectivity with fluorescent guests. 

Water can be removed from methanol by a membrane of polyvinyl alcohol cross-linked with polyacrylic acid, with a separation factor of 465.204 A polymeric hydrazone of 2,6-pyridinedialdehyde has been used to dehydrate azeotropes of water with n- and /-propyl alcohol, s- and tort butyl alcohol, and tetrahydrofuran.205 The Clostridium acetobutylicum which is used to produce 1-butanol, is inhibited by it. Pervaporation through a poly(dimethyl-siloxane) membrane filled with cyclodextrins, zeolites, or oleyl alcohol kept the concentration in the broth lower than 1% and removed the inhibition.206 Acetic acid can be dehydrated with separation factors of 807 for poly(4-methyl-l-pentene) grafted with 4-vinylpyridine,207 150 for polyvinyl alcohol cross-linked with glutaraldehyde,208 more than 1300 for a doped polyaniline film (4.1 g/m2h),209 125 for a nylon-polyacrylic acid membrane (5400 g/m2h), and 72 for a polysulfone.210 Pyridine can be dehydrated with a membrane of a copolymer of acrylonitrile and 4-styrenesulfonic acid to give more than 99% pyridine.211 A hydrophobic silicone rubber membrane removes acetone selectively from water. A hydrophilic cross-linked polyvinyl alcohol membrane removes water selectively from acetone. Both are more selective than distillation.212... 

This multicomponent catalytic system also made it possible to oxidize in high yields a wide range of straight-chain higher a-alkenes [24], However, the oxidation rate and the ketone selectivity were strikingly dependent on the nature of the cyclodextrin and on the chain length of the alkene (Figure 2). The alkene optimal size and shape was reached with 1-decene. Attempts to oxidize internal alkenes in biphasic medium with cyclodextrins modified in this way failed due to the lack of accessibility of the double bond in the inclusion complex. 

As already mentioned, isomerization (double bond shift) is also a side reaction, which reduces the selectivity of the oxidation of higher olefins. High selectivity with respect to the formation of methylketones is obtained with a system consisting of t-butyl hydroperoxide as the oxidant, acetonitrile as the solvent, and P-cyclodextrine as a phase transfer catalyst in the oxidation of 1-dodecene [80] and of higher olefins C22-C20 [81]. Also, modified P-cyclodextrines increase the selectivity and activity of a PdSO /CuSO /phosphomolybdovanadic acid catalyst in biphasic oxidation of 1-decene to 2-decanone [82,83]. 

The cyclodextrin ring does not have a well-defined depth, so we adopted a simple procedure to turn it from an open tube into a cup. We attached some flexible groups on the primary carbons of the cyclodextrin that could partially invade the cavity and produce a flexible floor.Later we studied acylation reactions with cyclodextrins that had been modified to include a floor on the bottom of the cavity - and also with improved substrates and a somewhat better solvent - that led to a relative rate of 750,000 compared with the uncatalysed hydrolysis rate at the same pH. When we looked at related compounds in which we had frozen out one of the degrees of freedom of the substrate the improvement came up to a 3,200,000-fold acceleration compared with the hydrolysis rate in water, and with some selectivity among the geometries of the complex. ... 

---