Crown ethers hydrophobic cavity

Macrocyclic ligands such as crown ethers have been widely used for metal ion extraction, the basis for metal ion selectivity being the structure and cavity size of the crown ether. The hydrophobicity of the ligand can be adjusted by attachment of alkyl or aromatic ligands to the crown. Impressive results have been obtained with dicyclohexano-18-crown-6 as an extractant for Sr in [RMIM][(CF3S02)2N] IL/aque-... 

Nakagawa, T., Murata, H., Shibukawa, A., Murakami, K., and Tanaka, H. (1985) Liquid Chromatography with Crown Ether-containing Mobile Phases V. Effect of Hydrophobicity and Cavity Size of the Crown Ether on Retention of Amino Compounds in Reversed-phase High-performance Liquid Chromatography, J. Chromatogr. 330, 43-53. 

The earliest recognised examples of synthetic supramolecular structures were the complexes formed from crown ethers and metal cations [19]. Since then numerous macrocycles have been synthesised. Representative examples are the cryptands [20], These differ from crown ethers in that the former contains a tridimensional cavity while the latter are characterised by a hole. Similarly, calix[4]arenes are compounds with a cup -like structure that through lower rim functionalisation gives rise to a hydrophilic and a hydrophobic cavity, thus allowing the reception of ionic species in the former and neutral species in the latter. Most of the above mentioned macrocycles are known for their capability to serve as cation receptors. 

An interesting conversion of a bis(styrene) crown precursor was reported recently <2001MI35>. The [2+21-photodimerization of 16 was found to occur in solution to afford a cyclobutane-containing crown ether. The reaction product was formed only in 10% yield when irradiated at >280 nm in aqueous base solution. However, when 7-cyclodextrin was present, the hydrophobic styryl residues were apparently confined within its interior cavity and the yield rose to 39%. A similar reaction was performed to afford the diaza-18-crown-6 derived cryptand. In the latter case, cyclization failed in the absence of the cyclodextrin (Figure 18). 

Inclusion complexing partners are classified as hosts and guests [46]. There are two types of hosts that were successfully employed in the chromatographic separation of enantiomers hosts that have a hydrophobic interior and hosts with a hydrophilic interior. The hydrophilic interior means that the cavity contains heteroatoms such as oxygen, where lone-pair electrons are able to participate in bonding to electron acceptors such as an organic cation (e.g., chiral crown ethers). In contrast, a host with a hydrophobic interior cavity is able to include hydrocarbon-rich parts of a molecule [47]. This type of host is found in the cyclodextrins. 

In type 111 CSPs, the solute enters into chiral cavities within the CSP to form inclusion complexes and the relative stabilities of the resulting dia-stereomeric complexes are based on secondary attractive (e.g., hydrogenbonding) or steric interactions. The driving force for the insertion can be hydrophobic (cydodextrin and polymethacrylate CSPs) or electrostatic (crown ether CSP). The commerdally available CSPs based on these mechanisms are presented in Table 3. 

Microcrystalline cellulose triacetate, cyclodextrin- and crown ether-derived CSPs, as well as some chiral synthetic polymers, achieve enantiomer separation primarily by forming host-guest complexes with the analyte in these cases, donor-acceptor interactions are secondary. Solutes resolved on cyclodextrins and other hydrophobic cavity CSPs often have aromatic or polar substituents at a stereocenter, but these CSPs may also separate compounds that have chiral axes. Chiral crown ether CSPs resolve protonated primary amines. 

Pirkle or brush type bonded phases Helical chiral polymers (polysaccharides) Cyclodextrins and crown ethers Immobilised enzymes Amino acid metal complexes Three-point interaction Attractive hydrophobic bonding Host guest interaction within chiral cavity Chiral affinity Diastereomeric complexation... 

The ability of cyclodextrins to give inclusion or "host-guest" complexes by insertion of various organic and inorganic molecules into their hydrophobic cavity is well-known. But these cavities are remarkably rigid. We have produced a crown ether-like compound starting from beta-cyclodextrin, in which the inner cavity is enlarged and more flexible. 

Macrocycles are classic small molecules in supramolecular chemistry. Examples of macrocycles include crown ethers, CDs, and calixarenes, as shown in Figure 2, which are used in biosensors. For sensing properties, cavity size is the most important factor. However, other supramolecular interactions, such as the hydrophobic effect, electrostatic interaction, van der Waals force, and hydrogen bonding, are also involved. 

A number of factors influence the separation which can be achieved. The shape of the molecule and its polarity determine whether it will be able to enter the hydrophobic cavity of the cyclodextrin. Vt varying the concentration of cyclodextrin, one can influence the partition of the complex between the selective and bulk phase. One can also modify the cyclodextrin in a manner that changes its solubility or affects its electrophoretic mobility. Bile salts and crown ethers have also been used as enantioselective agents. 

Since 1991 we have developed the synthesis of macropolycycles containing in their molecular structure the monocyclic structure of calixarenes and crown ether elements. This combination gives a close coupling of the hydrophobic cavity of the calixarenes able to include organic substrates and the metal cation complexing sites of the crown ether, with potential interactions between them. We have already demonstrated evidence of such cation-substrate contact during a triple inclusion by a calixarene [10]. The crystal structure of the Eu(III) complex of his-(homooxa)-p-rerr-butylcalix[4]arene showed the Eu(in) to be coordinated to a DMSO molecule included in the hydrophobic cavity of the calixarene [10]. 

Chiral crown ether selectors are derivatized forms of polyoxyethylene crown-6 [27]. This crown ether has a cavity that exactly match the size of an ionized primary amine group, -NHs". The host-guest ammonium-crown ether interaction, one point of attachment, is the driving force of the enantiomer with this class of chiral selector. The two other necessary interactions are a steric and a hydrophobic one. They will occur between the crown ether substituents and the host substituent. Chiral crown ether can only discriminate chiral molecules with a primary amine group at low pH (where the amine is protonated). 

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