Calixarenes, stationary phases

Recently the separation of enantiomers by RIfS and SPR using calixarenes with chiral amide residues was demonstrated [19]. Chirasil-Calix (Fig. 7) is well known from capillary GC as a stationary-phase material because of its good thermal and long-term stability. The separation of amino acid derivatives and lactic esters was widely studied [23]. 

Among more complex macrocycles, Li et al. [47-52] reported the preparation and characterization of stationary phases incorporating calixarenes or calix-crowns bonded to silica. With individual columns, high selectivity was observed in the separation of alkylated aromatics, aromatic carboxylic acids, sulfonamides, nucleosides, and water-soluble vitamins. In other work, Sokoliess et al. [53] have characterized calixarene- and resorcinarene-bonded stationary phases similar to those described in the previous section of this chapter. And Huai et al. [54] used an end-capped p-tert-butyl-calix[4]arene-bonded silica phase for HPLC separation of a number of organic compounds. Resorcinarenes have also found application in GC. [55-57] Recently, exotic macrocycles have been used in capillary electrochromatography, as reported by Gong et al. [58]... 

Sokoliess, T., Menyes, U., Roth, U., and Jira, T. (2002) Separation of Cis- and Trans-isomers of Thioxanthene and Dibenz[b,e]oxepin Derivatives on Calixarene- and Resorcinarene-bonded High-performance Liquid Chromatography Stationary Phases, J. Chromatogr. A 948, 309-319. 

Milbradt, R. and Bohmer, V. (2001) Calixarenes as stationary phases, in Asfari, Z. (ed.), Calixarenes, Kluwer Academic Publishers, Dordrecht, pp. 663-676. 

The efficient separation of the geometrical isomers of clopenthixol 252, X = C1, flupentixol 252, X = CF3, and chloroprothixene 253 has been accomplished using calixarene- and resorcinarene-bonded stationary phases in high-performance liquid chromatography <2002JCH(948)309> and innonaqueous capillary electrophoresis <2003ELP1648>. 

A fulleropyrrolidine derivative has been synthesized and covalently linked to HPLC silica gel and the resultant material was used to separate calixarenes, cy-clodextrins, and protected peptides [271]. Another type of organofullerene material containing polysiloxane was recently synthesized. It was found to be suitable for separating high-boiling-point compounds, and can be found applications as the stationary phase in capillary gas chromatography [272]. 

The area covered is very widespread and the role of the calixarene molecules reach from a simple platform or skeleton on which to assemble chiral centers to an inherent part of the chiral structure. Biologically active molecules or derivatives are involved as well as artificial ligands and their metal complexes. Chiral calixarenes have been used as stationary phases in analytical separations or as host molecules in sensors. Basic properties of calixarenes, such as their conformational stabilities, have been studied with chiral derivatives as well as more... 

The synergistic effect was only found in mixed stationary phases that have a special selectivity. Those stationary phases were CD, crown ether, liquid crystal-hne, resorcarene, calixarene, AgNOs, and others. Crown ether, CD, cahxarene, and resorcarene possess cyclic moieties with cavity-like structures that are able to form inclusion complexes with metal ions and organic molecules. Liquid crystalhne stationary phases have temperature-dependent ordered structures and the retention is governed by the solute s length-to-breadth ratio. AgNOs retards olefins by the formation of loose adducts. Together with the above special selectivity stationary phases, they have already been the focal point of sup-ramolecular chemistry. 

Polycarboxylate crown ethers such as (205) are suitable ligands for potentiometric studies of mixed-metal complexes of Al3+ and alkali or alkaline-earth cations.303 A similar (+)-18-crown-6-tetracarboxylic acid, chemically immobilized on a chiral stationary phase (CSP), can selectively recognize both enantiomers of some analytes.304 Calixarene polycarboxylates such as (206) and (207) are useful ligands toward alkali-305,306 and also transition-metal ions,307 308 with applications in... 

R. Milbradt and V. Bohmer, Calixarenes as Stationary Phases, in Reference lb, p. 663. 

The effect of the presence of crown ethers in the eluents [7,33], or in the stationary phases [34-37] on the effectiveness of separation of alkali metals on cation exchangers has been investigated. Higher selectivity of Na separation was observed on silica resins impregnated with calixarene [38]. 

Relatively few molecular separations have been studied from the utilitarian standpoint. One of these, the purification of fullerenes via 8 , is discussed on p. 170. In a reciprocal experiment the separation of 4 " , 6 , and 8 with a column using a chemically-bonded C o silica stationary phase has been re-ported. Chromatographic selectivity has been achieved for amino acid esters and alkali metal cations on silica-bonded calix[4]arene tetraesters, the structure of which has been explored by and Si-CP-MAS NMR. Silica-bonded calixarenes have also been used as packing materials for HPLC columns that are capable of separating disubstituted aromatics, peptides, and nucleosides. The HPLC separation of phenols using 6 ° as a constituent of the eluent has been described. ... 

Calixarenes have been extensively studied as solvent extractants for inorganic ions, stationary phases for capillary gas chromatography (GC), selectivity modifiers in CE, and as components of HPLC. The calixarene structure is quite versatile in that the lower rim can be modified to adjust solubility and the phenol groups on the upper rim are suitable for many chemical modihcations that may introduce specific selectivity. Here, we describe the application of modified calixarenes to ion chromatographic separations. 

Arena and colleagues modified calixarenes with crown ethers and covalently bonded them to siUca gel to serve as an IC stationary phase. These caUx-crown phases showed satisfactory separations among Na+, K+, and Cs+. However, the columns were operated at a rather low flow rate, so the separation time was long (about 20 min) when using mixed methanol/water eluents. 

Since calixarenes can be functionalized almost at will at their upper or lower rim, they represent good candidates for new stationary phases. Similar to cyclodextrins, guests can in principle be inserted into the hydrophobic interior of the cone-shaped macrocycles. To this end, calixarenes of different ring sizes have been immobilized on silica gel and were studied with respect to their discrimination between nucleosides and nucleobases in HPLC separations. 

Early attempts to use calixarenes as new stationary phases in the HPLC of biomolecules focussed on silica gel materials with a short hydrophilic linker between the silanol groups and the phenolic OH groups at the lower rim (Fig. 24.30). However, the new materials behaved more or less like reversed phases, and separated nucleobases according to their polarity increase [93]. 

When ferf-butyl calix[8]arenes were immobilized on silica gel from a 3-glycidoxypropyl-bonded stationary phase (GBS) precursor, nucleosides and bases were strongly retained inside the mobile calixarene cavity and led to much better separation on the advanced stationary phases, especially in mobile phases with a large water content [95]. 

From 9d the tetrapropyl ether could be prepeired in the cone conformation and resolved by chromatography on chiral stationary phases [12]. Thus, the first single enantiomer of an inherently chiral calixarene was obtained. 

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