Preparation Of Magnetic Porous Molecular Imprinting Materials For Drug Residue Analysis

With health consciousness improving,people pays increasingly attention to drug residues,and puts forward more and more strict requirement for its analysis technology.However,due to the highly complex matrix of biological samples,it is generally required tedious and time-consuming pretreatment steps prior to analysis.In essence,molecularly imprinted polymers（MIPs）is one synthetic material with tailor-made recognition sites for target molecule,which plays an important role in sample pretreatment technologies.Till now,it has been established for the mechanism and preparation method of MIPs.However it should be comprised among adsorption capacity,mass transfer rate,selectivity and specificity when applied in practice,which is limited by its instinct characterization.To overcome the bottleneck,a new strategy,developed two new methods were proposed,and 3novel MIPs were preparaed in the thesis.The details are listed below:1)Preparation of norfloxacin porous magnetic molecularly imprinted polymersOne novel porous magnetic molecularly imprinted polymer was designed for norfloxacin（NFX-mMIP）via oil-in-water emulsifier-free emulsion method.It was prepared by one-pot simply mixing norfloxacin,methacrylic acid-co-ethylene glycol dimethacrylate copolymer,and Fe₃O₄ together at room temperature.NFX-mMIP was characterized by multiply analytical methods.The particle pore size,pore volume and specific surface area of the product are about 10–500 nm,2.92 m L/g and 105.84 m²/g,respectively.And it also exhibits good magnetic responsiveness,and the solid-liquid separation could be achieved within 15 s with the assistant of external magnetic field.The isothermal binding experiment shows the saturated adsorption capacity of NFX-mMIP reaching 27.04 mg/g,the kinetics binding experiment shows that the adsorption behavior is well matched the pseudo-second-order kinetic model.Moreover,it is applied to enrich trace NFX in lake water and pork liver,separately.The results demonstrate NFX-mMIP having high selectivity and specificity towards NFX,as well as fast binding speed and relatively convenient operation steps.Furthermore,it can be sussessfully applied to enrich NFX low to 30 ng/g in pork liver,about 100 times less than the maximum residue limit regulated by Commission of the European Communities.The results were validated by HPLC assays.The above results demonstrated that NFX-mMIP can be used in practice for monitoring NFX either in environmental water or meat product with high accuracy and reliability.Compared with traditional imprinted materials,it has many mertis,such as preparation process simple,adsorption capacity high and adsorption time short.2)Preparation of magnetic molecular imprinting locks with adjustable holesIt is based on“stiff”cavities to recognize the target molecules for traditional MIPs.Those stiff cavities are with fixed morphologies and provide the specificity and selectivity of MIPs,but it significantly limits template molecules transfering in/out MIPs.Therefore,MIPs cannot meet the requirements of high-throughput binding in practical applications.In this work,the immobilized metal affinity chromatography（IMAC）mechanism is innovatively introduced into the preparation of mMIPs.The generated coordination bond is utilized to guarantee selectivity and specificity of mMIP,which is one special"soft"covalent bond.In this work,it was used.Copper salt,OTC,poly（St-co-ITA）and Fe₃O₄ magnetic fliud were mixed together by one modified oil-in-water emulsifier-free emulsion technology or emulsifier-free emulsion technology to prepare mMIP.The product was denoted as CB-mMIP.The particles were characterized by multiply analytical methods.The particle size,saturation magnetization and specific surface area of the product are about 20–50μm,8.08emu/g and 35.53 m²/g,respectively.The isothermal binding experiment shows the saturated adsorption capacity of NFX-mMIP reaching 62.57 mg/g and an amazing imprinting factor（over 29）,the kinetics binding experiment shows that the adsorption behavior is well matched the pseudo-second-order kinetic model.In addition,the material also exhibited a wide range of p H application and good reusability.Moreover,it was successfully applied to enrich trace OTC in pork liver and validated by independent HPLC assays.The results demonstrate CB-mMIP having high selectivity and specificity towards OTC,as well as fast binding speed and relatively convenient operation steps.Cu（II）as both the"bridge"group and predetermined orientation of functional moieties,to prepare a three-dimensional structure that fits the template molecule.This accurate structure just as one lock only responds to one key.At the same time,by adding oxalic acid,the coordination bond was quickly broken,and the size of imprinted holes can be adjusted to improve the mass transfer rate.The strategy holds promise as a reliable,extensible,and versatile approach and it breaks through the limits of traditional MIPs synthesis strategy,it provides a new direction or mechanism to design and synthesize MIPs with high efficiency,high selectivity,high binding capacity and high mass transfer rate.3)Preparation of"brush"type magnetic surface molecularly imprinted polymerFor traditional imprinting methods,it is effective to imprint small molecular compounds with a molecular weight（MW）between 300 and 500.Once MW rather increasing,the performance of MIPs will significantly decrease.In this work,the proposed mechanism and the surface imprinting technology were combined to prepare a"brush"surface mMIPs with adjustable hole on the surface of the magnetic beads by gel-sol method.Cu（II）,magnetic beads,TYL（TYL,MW:916）and itaconic acid were mixed together for 15 min under ultrasonic.And then N,N’-methylenebisacrylamide was added.The recation was further performed for 24 h at 65^oC.The product was obtained and donated as TYL-mMIP.The particles were characterized by multiply analytical methods.The particle size and saturation magnetization the product is about 400–700 nm and 8.08 emu/g,respectively.And it also exhibits excellent magnetic responsiveness,and the solid-liquid separation could be achieved within 5 s with the assistant of external magnetic field.The isothermal binding experiment shows the saturated adsorption capacity of TYL-mMIP reaching 10.87 mg/g and imprinting factor beyond 6.The kinetics binding experiment showed that the adsorption behavior was well matched pseudo-second-order kinetic model and the adsorption equilibrium was achieved within 5 min.Moreover,it is successfully applied to enrich trace TYL in human urine and validated by independent HPLC assays.The results demonstrate TYL-mMIP having high selectivity and specificity towards TYL.Compared to convectional method for surface MIPs,the proposed is much simpler and with faster mass transfer rate.Emphasized,it is highly hydrophilic that is helpful for operating.The proposed method provides a new accurate imprinting strategy for preparation of surface mMIPs with larger molecular weight.