Methacrylic acid-ethylene glycol dimethacrylate MIPs

A similar concept was used in the development of artificial chymotrypsin mimics [54]. The esterase-site was modeled by using the phosphonate template 75 as a stable transition state analogue (Scheme 13.19). The catalytic triad of the active site of chymotrypsin - that is, serine, histidine and aspartic acid (carboxy-late anion) - was mimicked by imidazole, phenolic hydroxy and carboxyl groups, respectively. The catalytically active MIP catalyst 76 was prepared using free radical polymerization, in the presence of the phosphonate template 75, methacrylic acid, ethylene glycol dimethacrylate and AIBN. The template removal conditions had a decisive influence on the efficiency of the polymer-mediated catalysis, and best results were obtained with aqueous Na2CC>3. 

Another example of new sorbents is the molecular imprinted polymers (MIP) from the work of Siemann and co-workers (1996). They synthesized a methacrylic acid-ethylene glycol dimethacrylate copolymer with atrazine as an imprint molecule. Imprint synthesis entails polymerization around an imprint species with monomers that are selected for their ability to form specific and definable interactions with the imprint molecule. The atrazine is chemically removed from the polymer leaving holes or cavities. The cavities are formed in the polymer matrix whose size and shape are complementary to that of the imprint molecule (Siemann et al., 1996). These recognition sites enable the polymer to rebind the imprint species selectively from a mixture of closely related compounds, in many instances with binding affinities approaching those demonstrated by antigen-antibody systems. 

The fact that a large number of templates has been successfully imprinted using basic recipes has led to the proliferation of MIPs of relatively low complexity, most of which have been based on a restricted number of synthetic trials (even though in some cases supported by spectroscopic or computational hints). The majority of basic templates have been imprinted using methacrylic acid (MAA) as monomer (seeTable 5.6A in Ref. 1), the acidic ones using vinylpyridines (VPY) (seeTable 5.6B in Ref 1). Ethylene glycol dimethacrylate (EDMA) is the most used crosslinker (see Table 2.5 in Ref 1), acetonitrile, dichloromethane, chloroform, toluene the most used solvents. 

Traditional noncovalent MIPs employ functional monomers such as methacrylic acid (MAA) or 4-vinylpyridine (4-Vpy) and cross-linking monomers such as divinyl benzene (DVB), ethylene glycol dimethacrylate (EDMA), or trimethylolpropane... 

Imprinted polymer membranes are prepared using atrazine as the template, methacrylic acid as a functional monomer, and tri(ethylene glycol) dimethacrylate (TEDMA) as a cross-linker. The molar ratio of the functional monomer to the template is 5 1. This ratio has to be optimized for each template. In order to obtain thin, flexible and mechanically stable membranes, oligourethane acrylate (molecular mass 2600) is added to the monomer mixture. Preparation of the molecularly imprinted polymer membrane is done as follows. Atrazine (20 mg) is mixed with methacrylic acid (40 mg), TEDMA (289 mg), oligourethane acrylate (51 mg), AIBN (2 mg) and 30% v/v of chloroform. Then a 60-120 pm gap between two quartz slides is filled with the monomer mixture. To initiate polymerization, the slides with the mixture are exposed to UV radiation (365 nm, intensity 20 W m ) for 30 min. After polymerization, atrazine is extracted with ethanol in a Soxhlet apparatus for 2h. This should not cause any visible changes in the MIP membrane. A membrane for control experiments can be prepared similarly except that no atrazine is added to the monomer mixture. 

V. Thibert et al. developed an MIP for the extraction of cocaine and its metabolites, i.e. benzoylecgonine and ecgonine methyl ester from urine prior to LC-MS procedure. They used cocaine as the template during the polymerization of methacrylic acid monomers in combination with ethylene glycol dimethacrylate cross-linker. The polymerization reaction was performed in acetonitrile and azo-N,N/-bis-isobutyroni-trile was used as the initiator. The LOQs for cocaine, benzolecgonine, and methyl ester, after separation and preconcetration through the MIPs, were evaluated to be 0.09 ng/ mL, 0.4 ng/mL, and 1.1 ng/mL respectively [243]. 

The selective extraction of catecholamines has been the subject of some studies [250,269]. Recently B. Claude et al developed a method for the selective SPE of catecholamines and metanephrines from bovine serum using MIPs, and reported the recovery, RSD and linearity range of the method to be in the orderof64-98%, less than 6% and 0.30-0.90 pM respectively [250]. In another study M. Bouri et al reported the selective extraction of catecholamines from urine using a dopamine MIP coated magnetic molecularly imprinted polymer and capillary electrophoresis. They used methacrylic acid as the monomer, ethylene glycol dimethacrylate as the cross-Unker and coated the MIP on FCjO particles and used 2,2 - azobisisbutyronitrile as the initiator in methanol/water or acetonitrile/water solvents, and reported LOD of 0.04-0.06 pM, RSD of 0.7%-1.4% and a response range of 2.9%-5.5% [269]. 

Acetaminophen and aspirin specific MIPs have also been prepared based on meth-acryhc acid, 4-vinylpyridine and methyl methacrylate as the monomer and ethylene glycol dimethacrylate as the cross-Hnking aganet [251]. MIPs have further been used... 

Guo et al. reported a potentiometric tetracycline selective MIP electrode using tetracycline as template, methacrylic acid as the functional monomer, and ethylene glycol dimethacrylate as crosslinker during the polymerization of the MIP in a methanol-water... 

In the case of clenbuterol, two sensors have been developed based on MIPs. The first report was on a flow chemiluminescence sensor based on the enrichment of nanogram amounts of clenbuterol by an MIP (methacrylic acid functional monomer, ethylene glycol dimethacrylate crosslinker), and the chemiluminescence reaction between potassium permanganate and formaldehyde in polyphosphate enhanced by clenbuterol. The system revealed linear response in the range of 1.0 x 1g/mL to 5.0 X 10 g/mL with a detection limit of 3.0 X 10 ° g/mL [434]. The other report covered an MIP-based poten-tiometric sensor based on the same MIP, which was reported to exhibit a Nernstian response in the rather wider, and yet higher range of 1.0 x 10" M to 1.0 X 10 M with an LOD of 7.0 X 10- M [377]. 

Javanbakht et al. reported an MIP-based potentiometric sensor for cetirizine [429]. The MIP was based on cetirizine dihydrochloride template, methacrylic acid functional monomer and ethylene glycol dimethacrylate crosslinker and was prepared using 2,2 -azobisisobutyronitrile initiator in chloroform. The potentiometric sensor showed a linearity range and detection Hmit of 1.0 X 10" —1.0 X 10" M and 7.0 X 10 M respectively [429]. 

EIS was also used by Peelers et al. [99] to quantify the concentration of serotonin in blood plasma. MIP were prepared using a mixture of methacrylic acid and acrylamide as functional monomers. The polymerization with ethylene glycol dimethacrylate was conducted in a UV-oven during 12 h. MIP particles of 25 pm were synthesized with this method. The template molecules of serotonin were removed by extraction with solvents. The MlPs were placed on the electrode using an adhesive polymer. The flow cell for serotonin measurement had two channels in order to measure the response on the MIP (active channel) and on the NIP (reference channel) simultaneously. One main advantage of this sensor is that serotonin can be measured in blood plasma directly. 

Molecular imprinted polymers (MIPs) can be prepared according to a number of approaches that are different in the way the template is linked to the functional monomer and subsequently to the polymeric binding sites. The current technique makes use of noncovalent self-assembly of the template with functional monomers before polymerization, free radical polymerization with a cross-linking monomer, and then template extraction followed by rebinding by noncovalent interactions. The functional monomer is often methacrylic acid, the cross-linker is ethylene glycol dimethacrylate, the initiator is 2,2-azo-A,lV -to-isobutyronitrile. They are mixed with template and the mixture is reacted at elevated temperature. The resultant rigid polymer is ground into a sieved powder and the template enantiomer washed off. 

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