Molecular imprinting techniques

Some restrictions of this molecular imprinting technique are obvious. The template must be available in preparative amounts, it must be soluble in the monomer mixture, and it must be stable and unreactive under the conditions of the polymer-... 

Some limitations of this molecular imprinting technique are obvious the template must be available in preparative amounts, it must be soluble in the monomer mixture and it must be stable and unreactive under the conditions of the polymerization. The solvent must be chosen considering the stability of the monomer-template assemblies and it should result in the porous structure necessary for rapid kinetics of the template interaction with the binding sites. If these criteria are satisfied, a robust material capable of selectively rebinding the template can be easily prepared and evaluated in a short period of time. 

Stationary phases with specific molecular recognition properties for D,L-enantiomers of peptides have been tailored using the molecular imprinting technique. A template molecule is added to suitable monomer(s), the system is polymerized, and the chiral template molecule is washed out [128]. 

The most popular and commonly used chiral stationary phases (CSPs) are polysaccharides, cyclodextrins, macrocyclic glycopeptide antibiotics, Pirkle types, proteins, ligand exchangers, and crown ether based. The art of the chiral resolution on these CSPs has been discussed in detail in Chapters 2-8, respectively. Apart from these CSPs, the chiral resolutions of some racemic compounds have also been reported on other CSPs containing different chiral molecules and polymers. These other types of CSP are based on the use of chiral molecules such as alkaloids, amides, amines, acids, and synthetic polymers. These CSPs have proved to be very useful for the chiral resolutions due to some specific requirements. Moreover, the chiral resolution can be predicted on the CSPs obtained by the molecular imprinted techniques. The chiral resolution on these miscellaneous CSPs using liquid chromatography is discussed in this chapter. 

The CSPs prepared by the molecular imprint technique have also been used for chiral resolution by CEC [98-100]. Lin et al. [91] synthesized L-aromatic amino acid-imprinted polymers using azobisnitriles with either photoinitiators or thermal initiators at temperatures ranging from 4°C to 60° C. Methacrylic acid (MAA) was used as the functional monomer and ethylene glycol dimethacrylate (EDMA) was used as the cross-linker. The resulting polymers were ground and sieved to a particle size less than 10 pm, filled into the capillary columns, and used for enantiomeric separations of some amino acids at different temperatures. The relationships of separation factor and column temperatures were demonstrated to be linear between the logarithm of the separation factors and the inverse of the absolute temperature (Fig. 24). The authors also compared the obtained chiral resolution with the chiral resolution achieved by HPLC and reported the best resolution on CEC. The chromatograms of the chiral resolution of dl-... 

In spite of the development of more successful and reliable CSPs (Chaps. 2-8), these miscellaneous types of CSP have their role in the field of the chiral resolution also. The importance of these CSPs ties in the fact that they are readily available, inexpensive, and economic. Moreover, these CSPs can be used for some specific chiral resolution purpose. For example, the CSP based on the poly(triphenylmethyl methacrylate) polymer can be used for the chiral resolution of the racemic compounds which do not have any functional group. The CSPs based on the synthetic polymers are, generally, inert and, therefore, can be used with a variety of mobile phases. The development of CSPs based on the molecularly imprinted technique has resulted in various successful chiral resolutions. The importance and application of these imprinted CSPs lies in the fact that the chiral resolution can be predicted on these CSPs and, hence, the experimental conditions can be designed easily without greater efforts. Because of the ease of preparation and the inexpensive nature of these CSPs, they may be useful and effective CSPs for chiral resolution. Briefly, the future of these types of CSP, especially synthetic polymers and polymers prepared by the molecularly imprinted technique, is very bright and will increase in importance in the near future. 

In the molecular imprinting technique, a cross-linked polymer matrix is formed around a target analyte (the template). The precursor mixture contains a functional monomer which can interact with the template molecule by covalent or non-covalent bonding. After the polymerisation process, the functional groups are held in position by the polymer backbone and the template molecule is removed. The residual binding sites are complementary to the target molecules in size and shape. 

MATSUI J, KATO T, TAKF.UCHT T, SUZUKI M, YOKOYAMA K, TAMIYA E and KARUBE I (1993), Molecular recognition in continuous polymer rods prepared by a molecular imprinting technique , Anal Chem, 65, 2223-2224. 

The molecular imprinting technique, based upon a self-association of molecules to build up a binding site structure, requires an appropriate choice of the building blocks, e.g. functional monomers. Construction and screening of imprinted... 

Molecular imprinting technique was recently used to prepare highly selective tailor-made synthetic affinity media used mainly in chromatographic resolution of racemates or artiftcial antibodies [130-133]. A complex between the template molecule and the functional monomer is first formed in solution by covalent or non-covalent interactions (Figure 3.10). Subsequently, the three-dimensional architecture of these complexes is confined by polymerization with a high concentration of cross-linker. The template molecules are then extracted from the polymer leaving behind complementary sites (both in shape and functionahty) to the imprinted molecules. These sites can further rebind other print molecules. 

According to Dalgliesh [2], three active positions on the selector must interact simultaneously with the active positions of the enantiomer to reveal differences between optical antipodes. This is a sufficient condition for resolution to occur, but it is not necessary. Chiral discrimination may happen as a result of hydrogen-bonding and steric interactions, making only one attractive force necessary in this type of chromatography. Moreover, the creation of specific chiral cavities in a polymer network (as in molecular imprinting techniques) could make it possible to base enantiomeric separations entirely on steric fit. 

Abstract Recent progresses in molecularly imprinted metal-complex catalysts are highlighted in this chapter. Molecular imprinting is a technique to produce a cavity with a similar shape to a particular molecule (template), and the molecularly imprinted cavity acts as shape-selective reaction space for the particular reactant. The application of the molecular-imprinting technique to heterogeneous metal-complex catalysts is focused in the viewpoint of a novel approach in the design of shape-selective catalysis mimicking enzymatic catalysis. 

Suzuki A, Tada M, Sasaki T, Shido T, Iwasawa Y (2002) Design of catalytic sites at oxide surfaces by metal-complex attaching and molecular imprinting techniques. J Mol Catal A Chem 182-183 125... 

Meng Z, Yamazaki T, Sode K (2003) Enhancement of the catalytic activity of an artificial phosphotriesterase using a molecular imprinting technique. Biotechnol Lett 25 1075... 

Yoshida, M. Hatate, Y. Uezu, K. Goto, M. Furusaki, S., Chiral-recognition polymer prepared by surface molecular imprinting technique, Colloids Surf A. 2000, 169, 259-269... 

Scheme 1 Generalized depiction ofthe molecular imprinting technique 1—monomers a, b, and c form an attachment to complementary sites on the template. 2—The preassembled template-monomer complex is polymerized with a large excess of crosslinker. 3—The rigid polymer formed in this process retains an arrangement of functional elements complementary both in shape and spatial orientation to the template. 4—Removal of the template reveals a binding pocket or cavity, which can be used to recapture the template species.

Meng ZH, Sode K (2005) The molecular reaction vessels for a transesterification process created by molecular imprinting technique. I Mol Recogn 18(3) 262—266... 

Irrespective of how the problem is resolved, to evaluate accurately the contribution made by the molecular imprinting technique, the results obtained with the MIP should be viewed with respect to results obtained using a network with the same chemical composition synthesised in the same conditions but in the absence of the template molecule. 

Recent studies have shown the efficiency of antibodies and artificial receptors prepared by the molecular imprinting technique and demonstrated the possibility of their use in therapeutic trials [102,144]. Materials imprinted around diazepam (tranquilliser) and theophylline (broncho-dilator) templates have been found to have selectivities comparable to those of monoclonal antibodies and almost nil cross-reactions with related substances (Fig. 17) [102]. 

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