Silica chiral resolution using

The dramatically higher surface area of mesoporous silica in comparison to commercially available chromatographic grade silica enhances resolution of molecules by increasing capacity factors to allow effective separations of analytes. In this report, we illustrate the use of these types of silica in normal phase HPLC, reverse phase HPLC, and chiral HPLC. 

Stalcup et al. [44] reported an interesting effect of spacers on the chiral resolution of some drugs, namely, there was no chiral resolution without a spacer between the CD and the silica gel. Chankvetadze et al. [49] studied the effects of such spacers on the chiral resolution of certain drugs. Two types of spacer, 4,4 -diphenylmethane diisocyanate and hexamethylene diisocyanate, were used to... 

The use of antibiotic-based CSPs has been reported in capillary electrochromatography (CEC) for chiral resolution [60]. Teicoplanin CSP covalently bonded to silica gel was used to resolve the enantiomers of tryptophan and dinitrobenzoyl leucine by CEC [61]. Good levels of enantioselectivity were obtained with optimized separations. Vancomycin covalently bonded to silica gel was also evaluated in CEC for the chiral resolution of thalidomide and jS-adrenergic blocking agents under all the three mobile phase modes. The... 

Bhushan and Parsad [65] resolved dansyl amino acids on erythromycin impregnated thin-layer chromatographic (TLC) silica plates. The mobile phase used was different ratios of 0.5 M aqueous NaCl-acetonitrile-methanol. Further, Bhushan and Thiong o [66] achieved the chiral resolution of dansyl amino acids on silica TLC plates impregnated with vancomycin chiral selector. The mobile phase used for this study was acetonitrile-0.5 M aqueous NaCl (10 4 and 14 3, v/v). The chiral recognition mechanisms of antibiotic CSPs in sub-SFC, SFC, CEC, and TLC modes of chromatography were found to be similar to HPLC. 

Wainer et al. [77] presented a CSP based on a-chymotrypsin protein, and, initially, the chiral resolution of certain amino acids and amino ester was achieved on this protein CSP [14,77]. Later, this CSP was used for the chiral resolution of dipeptides and profens [78,79]. Recently, Felix and Descorps [80,81] used immobilized a-chymotrypsin for the chiral resolution of a variety of racemic compounds. Cellobiohydrolase-I (CBH-I) immobilized to silica gel was found to... 

In addition to the above-discussed parameters, other factors such as dimension of the column, particle size of the silica gel, and mobile phase additives may be considered for the optimization of chiral resolution on these CSPs. Metal ions often are important structural components in some proteins to organize conformation [112]. Therefore, the effect of metal ions as mobile phase additives may be useful. Oda et al. [74] used zinc ions as the mobile phase additive on avidin CSP to improve the chiral resolution of ibuprofen, chlormezanone, and other drugs. The results are summarized in Table 5, which indicates that the addition of zinc ions in the mobile phase has resulted into an improved resolution of some... 

It is well known that the chiral resolution of these CSPs occurred as a result of the exchange of ligands and enantiomers on the same metal ion. Therefore, these CSPs are suitable only for those racemates which can coordinate with the metal ion. Therefore, racemates like amino acids, amines, and hydroxy acids have been resolved successliilly by the ligand-exchange process. As mentioned earlier, either the individual chiral ligand or one complexed with a metal ion is bonded onto silica gel support. Therefore, in the case of the first type of CSP, the metal ion is used in the mobile phase no metal ion is required in the mobile phase in the latter case. 

The authors reported the chiral separation of proline and thereonine amino acid up to 20 and 6g, respectively, in a single run. Micropreparative resolution of lecucine was presented. The resolution was discussed with respect to the degree of sorbent saturation with copper(II), elution rate, eluent concentration, temperature, and column loading condition [16]. Weinstein [74] reported the micropreparative separation of alkylated amino acids on a Chiral ProCu column. In another article, a preparative chiral resolution of 3-methylene-7-benzylidene-bicyclo[3.3.1]nonane was achieved on 7.5% silver(I)-d-camphor- 10-sulfonate CSP [75]. Later, Shieh et al. [71] used L-proline-loaded silica gel for the chiral resolution of (ft,5 )-phcnylcthanolaminc as the Schiff base of 2-hydroxy-4-methoxyacetophenone. Gris et al. [76] presented the preparative separations of amino acids on Chirosolve L-proline and Chirosolve L-pipecolic acid CSPs. 

The CSPs based on chiral crown ethers were prepared by immobilizing them on some suitable solid supports. Blasius et al. [33-35] synthesized a variety of achiral crown ethers based on ion exchangers by condensation, substitution, and polymerization reactions and were used in achiral liquid chromatography. Later, crown ethers were adsorbed on silica gel and were used to separate cations and anions [36-39]. Shinbo et al. [40] adsorbed hydrophobic CCE on silica gel and the developed CSP was used for the chiral resolution of amino acids. Kimura et al. [41-43] immobilized poly- and bis-CCEs on silica gel. Later, Iwachido et al. [44] allowed benzo-15-crown-5, benzo-18-crown-6 and benzo-21-crown-7 CCEs to react on silica gel. Of course, these types of CCE-based phases were used in liquid chromatography, but the column efficiency was very poor due to the limited choice of mobile phases. Therefore, an improvement in immobilization was realized and new methods of immobilization were developed. In this direction, CCEs were immobilized to silica gel by covalent bonds. 

Machida et al. presented a method for the immobilization of CCE on silica gel in 1998 [45]. They reported the covalent binding of (+)-(18-crown-6)-tetracarboxylic acid to 3-aminopropylsilanized silica gel and the prepared CSP was tested to separate enantiomers of amino acids, amino alcohols and other drugs (containing primary amino group). In 1998, the same CSP was prepared by Hyun et al. [46]. The developed CSP was used extensively for the chiral resolution of a variety of racemic compounds having a primary amino group... 

In 1998, Machida et al. [45] and Hyun et al. [46] developed a new CCE-based CSP (covalently bonded to silica gel see Sect. 8.2). This CSP was used successfully for the chiral resolution of certain racemic compounds using a variety of mobile phases. The most important applications of this CSP are for the resolution of amino acids, amino esters, amino alcohols, amines, amides, quinolone antibacterials, and other drugs having primary amino groups [46-51,64,65]. The typical chromatograms of the chiral resolution of amino acids on (+)-(18-crown-6)-2,3,ll,12-tetracarboxylic acid CSP are shown in Figure 4. The enantiomeric resolution of the racemic compound on CCE-based CSPs are listed in Table 2. There is no report available on the chiral separations at the preparative scale using these CSPs. 

Cholic acid and 3-phenylcarbamoyl cholic acid allyl esters were grafted to hydride-activated silica gel and the developed CSPs were used for the chiral resolution of derivatized amino acids, amines, alcohols, hydantoins, and 2,2 -... 

The synthesis of optically active polymers is an important area in macromolecular science, as they have a wide variety of potential applications, including the preparation of CSPs [31-37]. Many of the optically active polymers with or without binding to silica gel were used as CSPs and commercialized [38]. These synthetic polymers are classified into three groups according to the methods of polymerization (1) addition polymers, including vinyl, aldehyde, isocyanide, and acetylene polymers, (2) condensation polymers consisting of polyamides and polyurethanes, and (3) cross-linked gels (template polymerization). The art of the chiral resolution on these polymer-based CSPs is described herein. 

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