Amino acid derivatives imprinting with

Several selective interactions by MIP membrane systems have been reported. For example, an L-phenylalanine imprinted membrane prepared by in-situ crosslinking polymerization showed different fluxes for various amino acids [44]. Yoshikawa et al. [51] have prepared molecular imprinted membranes from a membrane material which bears a tetrapeptide residue (DIDE resin (7)), using the dry phase inversion procedure. It was found that a membrane which contains an oligopeptide residue from an L-amino acid and is imprinted with an L-amino acid derivative, recognizes the L-isomer in preference to the corresponding D-isomer, and vice versa. Exceptional difference in sorption selectivity between theophylline and caffeine was observed for poly(acrylonitrile-co-acrylic acid) blend membranes prepared by the wet phase inversion technique [53]. 

Table 6-3. Resolution of amino acid derivatives on a MIP imprinted with L-phenylalanine anilide (L-PA).

A number of studies have recently been devoted to membrane applications [8, 100-102], Yoshikawa and co-workers developed an imprinting technique by casting membranes from a mixture of a Merrifield resin containing a grafted tetrapeptide and of linear co-polymers of acrylonitrile and styrene in the presence of amino acid derivatives as templates [103], The membranes were cast from a tetrahydrofuran (THF) solution and the template, usually N-protected d- or 1-tryptophan, removed by washing in more polar nonsolvents for the polymer (Fig. 6-17). Membrane applications using free amino acids revealed that only the imprinted membranes showed detectable permeation. Enantioselective electrodialysis with a maximum selectivity factor of ca. 7 could be reached, although this factor depended inversely on the flux rate [7]. Also, the transport mechanism in imprinted membranes is still poorly understood. 

Table 6.5. Rebinding data for I- and D-enantiomers in Ti02-gel films imprinted with Cbz-amino acid derivatives...

Imprinted Ti02-gel films were prepared in a similar way by using L- or D-amino acid derivatives (Cbz-Ala, Cbz-Leu, Cbz-Phe) as templates. The template molecule is removed by treating with 0.1 wt % aqueous ammonia. The rebinding data for the l- and D-enantiomers in these imprinted films are shown in Table 6.5. The enantioselectivity factor (a) in each imprintedfilm is a ratio of... 

Mosbach prepared imprinted polymers with not only a more specific substrate binding but with a true catalytic turnover [148]. Certain N-protected amino acid derivatives formed pseudotetrahedral complexes in solution in the presence of Co and two molecules of 5-vinylimidazole. These were polymerised in the presence of divinylbenzene and the metal-ion and amino acids eluted together afterwards. Hydrolysis of the corresponding 4-nitrophenylester of the amino acid template showed an increase in catalytic activity (factor 2-4) compared with a blank prepared without the template. The polymer also exhibits a clear preference for the activated ester of the template, which suggests that hydrolysis indeed takes place inside the cavities. Two years later the scope was further broadened by the preparation of the first polymer imprinted with a transition state analogue. 

Patrikeev et al. also employed imprinted silicas for thin layer chromatography. The silica was mixed with plaster and immobilised on a plate for use in the separation and identification of gramines [31] and for the resolution of amino acid derivatives [29]. In the latter experiment it was found that the influence of the amino acid protective group, dinitrophenol, was too dominant to allow the separation of... 

RESOLUTION OF AMINO ACID DERIVATIVES ON A MIP IMPRINTED WITH L-PA... 

The imprinting effects of MIPs prepared with optically active compounds as the print molecules are readily demonstrated by chromatographic evaluations. For example, when the L-enantiomer of an amino acid derivative is used as the print species, a column packed with the resulting polymer will retain the L-enantiomer longer than the o-enantiomer and vice versa when the o-enantiomer is used as the print molecule. Reference polymers prepared with the racemate or without print molecule will not be able to resolve the racemate. A steroselective memory is hence induced in the polymers by the print molecules and is in many cases very precise. 

Figure 6 Chiral HPLC separation of amino acid derivatives on imprinted stationary phases packed with Z-L-Glu-OH (a), Boc-L-phe-Gly-OEt (b), Z-L-Ala-L-Ala-Ome (c) Z-L-Ala-Gly-L-Phe-OMe (d). Mobile phase chloroform - acetic acid. Column 250 x 4.6 mm. Flow rate, 1 mL/min. Detection, UV 260 nm. Reproduced from Ref. 22, with permission.

Nanofibers are nanostructures with diameters in the nanometer range. They have been resourcefully used in sensing applications. Piperno and co-authors [72] immobilized polymer nanofibers in Imp-NPs for an amino acid derivative and used them in a fluorescence-based sensor for dansyl-L-phenylalanine detection. Polyfvinyl alcohol) was used as the supporting material with Imp-NPs, because it was water soluble and could be spun into very thin fibers. An Imp-nanofiber membrane was synthesized using N-a-benzyloxycarbonyl-D-glutamic acid (Z-D-Glu) or N-a-benzyloxycarbonyl-L-glutamic acid (Z-L-Glu) as imprint molecules for sensing of amino acid derivatives. Cellulose acetate was also used to synthesize Imp-nanofiber membranes by the electrospray method for the same analytes. 

Optical isomer separations that are carried out on a chiral layer produced from C-18 modified silica gel impregnated with a Cu(II) salt and an optically active enantiomerically pure hydroxyproline derivative, on a silica layer impregnated with a chiral selector such as brucine,on molecularly imprinted polymers of alpha-agonists,or on cellulose with mobile phases having added chiral selectors such as cyclodextrins have been reported mostly for amino acids and their derivatives. Mixtures of sorbents have been used to prepare layers with special selectivity properties. 

The development of an imprinted network starts with the choice of the template molecule. It is this molecule that the material will keep in memory. The choice remains limited, however, by the functional monomers available and susceptible to interact. Depending on the domain studied, diverse molecules have been used (Fig. 5) amino acids [26],sugar derivatives [27], steroids [28], nucleotides [29], pesticides [30], dyes [12], drugs [31-36], metal ions [37-39], more inert molecules (like anthracene, benzene and its derivatives) [40-42], and even more complex molecules such as proteins or enzymes [43,44]. 

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