Chiral stationary phases metal complexes

Gc chiral stationary phases can be broadly classified into three categories diamide, cyclodextrin, and metal complex. 

Although the chiral recognition mechanism of these cyclodexttin-based phases is not entirely understood, thermodynamic and column capacity studies indicate that the analytes may interact with the functionalized cyclodextrins by either associating with the outside or mouth of the cyclodextrin, or by forming a more traditional inclusion complex with the cyclodextrin (122). As in the case of the metal-complex chiral stationary phase, configuration assignment is generally not possible in the absence of pure chiral standards. 

Chiral Chromatography. Chiral chromatography is used for the analysis of enantiomers, most useful for separations of pharmaceuticals and biochemical compounds (see Biopolymers, analytical techniques). There are several types of chiral stationary phases those that use attractive interactions, metal ligands, inclusion complexes, and protein complexes. The separation of optical isomers has important ramifications, especially in biochemistry and pharmaceutical chemistry, where one form of a compound may be bioactive and the other inactive, inhibitory, or toxic. 

Complexation with Chiral Metal Complexes. This idea was first suggested by Feibush et al.44 The separation is realized by the dynamic formation of diastereomeric complexes between gaseous chiral molecules and the chiral stationary phase in the coordination sphere of metal complexes. A few typical examples of metal complexes used in chiral stationary phase chromatography are presented in Figure 1-13.45... 

Analysis using a CMPA is usually resolved on a nonchiral column. A transient diastereomeric complex is formed between the enantiomer and the chiral component in the mobile phase, similar to the complexes formed with chiral stationary phases. A review by Liu and Liu (2002) cites several papers where addition of CPMAs has been used in analyzing amphetamine-related compounds. Some CPMAs include amino acid enantiomers, metal ions, proteins, and cyclodextrins. Advantages of this method of analysis include the use of less expensive columns and more flexibility in the optimization of chiral separation (Misl anova and Hutta, 2003). 

Ligand exchange chromatography is a very powerful method for separating enantiomers. However, it is limited to enantiomeric compounds that are able to undergo metal complexes with the chiral stationary phase such as amino acids, amino acid derivatives, and amino alcohols. 

The use of chiral stationary phases (CSP) in liquid chromatography continues to grow at an impressive rate. These CSPs contain natural materials such as cellulose and starch as well as totally synthetic materials, utilizing enantioselective and retentive mechanisms ranging from inclusion complexation to Ti-electron interactions. The major structural features found in chiral stationary phases include cellulose, starch, cyclodextrins, synthetic polymers, proteins, crown ethers, metal complexes, and aromatic w-electron systems. 

Compared to CMP, the mechanism of separation on a chiral stationary phase is easier to predict, due to a much simpler system. Because the ligand is immobilized to a matrix and is not constantly pumped through the system, the detection limits for the enantiomers are much lower. Depending on the ligand immobilized to the matrix, one can have different types of interactions between the selectand and selector metal complexes, hydrogen-bonding, inclusion, tt-tt interactions, and dipole interactions, as well as a combination thereof. 

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... 

A chiral stationary phase is used comprising a silica substrate on which is fixed an amino acid. The mechanisms developed are of the "ligand exchange" type. The distinction between two enantiomers is possible due to the formation of mixed diastereoisomerical complexes (chiral solute - transition metal - amino acid fixed on the silica substrate). The transition metal is added to the mobile phase. (Fig. 4)... 

Although packed columns have been used in earlier studies, capillary columns containing wall-coated or immobilized chiral selectors are more widely used at present. The chiral selector may be of different nature, such as amino acid derivatives, chiral metal complexes, etc. [90], At present, cyclodextrins (CD) and their derivatives dominate as chiral stationary phases (CSP) in GC enantioseparations [90, 91], CD-based CSPs for GC are thermally stable, widely applicable, and easy to use. 

Figure 10.4. Structures of immobilized poly(siloxane) chiral stationary phases containing (A) a cyclodextrin derivative (Chirasil-Dex) and (B) a metal complex (Chirasil-Nickel).

The direct resolution of underivatised enantiomers has been effected with the aid of some metal-containing chiral stationary phases. Particular attention has been paid to the resolution of chiral alkenes and epoxides using stationary phases derived from chiral metal chelate complexes. The rhodium dicarbonyl P-diketonate complex (5), when dissolved in squalene and coated onto a capillary column, permitted the quantitative enantiomer resolution of 3-methylcyclopentene while methyl oxirane was similarly resolved... 

The native CF6 chiral stationary phase produced chiral separations of a few primary amines and binaphthyl-type molecules using organic solvents as mobile phases (as shown in Fig. 5). The fact that no enantiomeric separations were observed in the reversed-phase mode indicates that effective chiral recognition at the hydrophobic surface of CF6 is not prevalent. Previous NMR studies of metal complexation of native and permethylated cyclofructans also reveal that the 3-OH and 4-OH groups are responsible for cyclofructan-metal cation interactions [30-32]. 

A large number of CCSPs were prepared in laboratory by several researchers owing to the ease of the impregnation procedures and the variety of chiral selectors used as impregnating agents (i.e., acids, bases, amino acids, and complexes with metal ions). In addition, as only little amounts of chiral selector were necessary for the impregnation of TLC sorbents, this technique was very cheap in comparison with chiral stationary phases (CSPs). 

The dependence of chiral recognition on the formation of the diastereomeric complex imposes constraints on the proximity of the metal binding sites, usually either an hydroxy or an amine a to a carboxyHc acid, in the analyte. Principal advantages of this technique include the abiHty to assign configuration in the absence of standards, enantioresolve non aromatic analytes, use aqueous mobile phases, acquire a stationary phase with the opposite enantioselectivity, and predict the likelihood of successful chiral resolution for a given analyte based on a weU-understood chiral recognition mechanism. 

The fundamental behaviour of stationary phase materials is related to their solubility-interaction properties. A hydrophobic phase acts as a partner to a hydrophobic interaction. An ionic phase acts as a partner for ion-ion interactions, and surface metal ions as a partner for ligand complex formation. A chiral phase partners chiral recognition, and specific three-dimensional phases partner affinity interactions. 

Even more generally applicable are GC columns with chiral metal chelates as stationary phases (complexation gas chromatography)26 (Table 6). Quite recently, chiral GC methods have been developed on the basis of cyclodextrin derived stationary phases27. 

A limiting factor of complexation gas chromatography is the low temperature range (25-120°C). Therefore, improved thermostable polymeric stationary phases, e.g., Chirasil-Metal, in which the chiral metal chelates are chemically anchored to a polysiloxane backbone, have been prepared155 156. 

Various Chiral-Metal stationary phases used in complexation gas chromatography have been described192, as are racemates which have been successfully resolved6. 

---