Study On Selection Of Cross-linkers And Templating Methods In Molecular Imprinting Technique

In this research, preparations of molecularly imprinted polymers (MIP) were studied, and an effective method, rational selection of the cross-linker in MIP design, was proposed. The dummy-template MIPs for Zidovudine were synthesized and used as solid-phase extraction sorbents, and then the SPE profile was optimized and used in the serum sample pretreatment. Utilizing dummy template and sacrificial template method, MIPs were prepared and the comparison was made. Immobilized template method was also used for the preparation of MIPs to study the amount of cross-linking agent on the imprinting effect. The main contents include:1. The best functional monomer and cross-linker were selected for zidovudine molecularly imprinted polymer by computer modeling. Choosing trimethylolpropane (TRIM), ethylene glycol dimethyl-acrylates (EGDMA), divinyl benzene (DVB) as cross linker and MAA as functional monomer, zidovudine molecularly imprinted polymers were prepared by dummy template method, and using4VP as functional monomer, nitrophenol molecularly imprinted polymers were prepared by traditional method. As well as, under the same experimental conditions, the corresponding control polymers (CP) were prepared using the three cross-linkers above without functional monomer. The binding constants, imprinting factors, adsorption capacities of all polymers in static adsorption and dynamic adsorption experiment were calculated. The imprinting effect was compared and proposed an effective method of rational selection of the cross-linker in MIP design. The results showed that DVB-based polymer had advantageous performances compared with the other two cross-linker based polymers for the preparation of AZT-imprinted polymer. And TRIM-based polymer had advantageous performances compared with the other two cross-linker based polymers for the preparation of4NP-imprinted polymer. For the CP, DVB was found as more inert towards zidovudine. TRIM was found as more inert towards nitrophenol. Finally, we proposed an effective method of rational selection of the cross-linker in MIP design; it proved that a cross-linker, which is most inert toward the template molecule, could be considered as the best for the preparation of molecularly imprinted polymer. It is possible to suggest that highly-specific molecularly imprinted polymers could be designed using computational modeling which selects the functional monomer with highest binding energies and a cross-linker with lowest binding energy towards the template.2. The dummy-template molecularly imprinted polymer of Zidovudine was used as solid-phase extraction sorbents, after optimization of SPE profile used in the serum sample pretreatment. It was determined that the best imprinting effect were obtained with loading in1mL of K-phosphate buffer pH=7, washing with1mL of2%(V/V)acetonitrile/phosphate buffer, eluting with hydrochloric acid:methanol=10:90. MIP and NIP showed high binding capacity in the buffer in breakthrough curve, and their capacity are9.10mg and1.77mg of drug/lg of adsorbent respectively. The dummy-template molecularly imprinted polymers were tested with zidovudine ester and lamivudine by adsorption experiment and showed comparatively high selectivity for AZT. The SPE eluent of AZT in spiked human serum was determined by HPLC, and recoveries of the analyte on MISPE and NISPE were99.3%and13.2%respectively. It was concluded that the dummy template MIP can be used for selective extraction of AZT serum sample without template bleeding.3.Using dummy template and sacrificing template method AZT and4-NP molecular imprinting polymer were prepared.Through the static adsorption experiment,the comparativity on the adsorption capacity of each polymers was studied.results show that,the imprinting efects and binding abilitys of the sacrificial spacer method molecularly imprinted polymers higher than Dummy-template molecularly imprinted polymers.4.Using immobilized template mathod the AZT mip was prepared with different ratio of cross-linker,the binding constant, imprinting factor, adsorption capacity for all polymers in static adsorption experiment were calculated and the amount of crosslinking agent on the imprinting effect was evaluated.results show that,use the immobilized template,significantly reduced the amount of crosslinking agent still can get better imprinting efficiency of molecularly imprinted polymer.