The Synthesis Of Iron-based Metal–organic Framework Composites And Their Application In Pharmaceutical Analysis

Metal-organic frameworks（MOFs）, also known as porous coordination polymers（PCPs）, emerging as a new class of porous crystalline materials, synthesized by assembling metal ions with organic bridging-ligands. Compared with conventional porous materials, the preeminent properties of MOFs such as flexible frame work topology, orderly tunable pores, ultrahigh specific surface area and unsaturated metal sites, make them have been widely used in gas storage, separation and enrichment, drug delivery, biological imaging, chemical sensing, catalysis and so on. Controllable integration of MOFs and other functional materials is leading to the creation of new multifunctional composites/hybrids, which exhibit new properties that are superior to those of the individual components through the collective behavior of the functional units. This is a newly developing interdisciplinary research area. Through the coordination of MOFs and other functional materials, this strategy has overcome the defects of MOFs and greatly expand the application range of MOFs. This thesis devoted to the synthesis of iron-based metal–organic frameworks and the composites, and investigated their application in pharmaceutical analysis as peroxidase mimic. This thesis includes the following parts:The application of Fe-MIL-88NH₂ in the visual detection of biological thiol compounds. As a preeminent peroxidase mimic, metal–organic framework Fe-MIL-88NH₂ could catalyze the oxidation of the peroxidase substrate 3, 3’, 5, 5’-tetramethylbenzidine（TMB） by H₂O₂ to develop a blue color in aqueous solution. However, when thiol compounds, such as cysteine（Cys）, homocysteine（Hcy） or glutathione（GSH）, existed in the solution, the color of the responsive solution gradually became pale due to the competitive reaction between TMB and thiol compounds with ·OH derived from the catalytic decomposition of H₂O₂, and the sulfydryl have been oxidized to form disulfide bond. Therefore, a sensitive and visual method for detection thiol compounds in serum has been established. The linear response ranges for Cys, Hcy and GSH were 1.0–80.0 μM, 1.0–80.0 μM and 1.0–100.0 μM, and the detection limits were 0.39 μM, 0.40 μM and 0.45 μM, respectively.The synthesis of Ag NPs/MIL-101（Fe） and the application in surface-enhanced Raman scattering（SERS） detection of dopamine（DA）. MOFs provides unique 3-D structures and ultrahigh surface area to attach plenty of SERS-active metal nanoparticles, it is possible to form abundant Raman hot spots if the metal nanoparticles could be anchored on the outer surface of MOFs, which contribute to enhance the SERS signal. In this study, the tannic acid（TA） as a reductant was first introduced onto MIL-101（Fe） through complexation of unsaturated Fe（III） on the surface of MIL-101（Fe） with hydroxyl groups in TA, making Ag NO₃ be directly reduced by TA on the surface of MIL-101（Fe） to engineer Ag NPs/MIL-101（Fe） complex structure. The composite combines the Raman enhancement effect of Ag NPs and the peroxidase-like activityof MOFs. The oxidation product of the ELISA colorimetric substrate 2,2’-azino-bis（3-ethylbenzthiazoline-6-sulfonic acid） diammonium salt（ABTS） resulted from the catalytic activity of MIL-101（Fe） in the presence of H₂O₂, and the enhanced Raman signal of oxidized-ABTS（ox-ABTS） would be detected. But the existence of DA would interdicted the oxidation process and and resulted in the loss of the Raman signal of ABTS2+. Hence, an ultrasensitive SERS method for the detection of DA was established. This new developed method showed good linearity in the range from 1.054 p M – 210.8 n M with the detection limit of approximately 0.32 p M.The preparation of Fe₃O₄/MIL-101（Fe） composites as highly active peroxidase mimetic for catalytic synthesis of phenazines. Fe₃O₄ NPs assembled on the surface of MIL-101（Fe） was facilely prepared through the electrostatic self-assembly technology. The research results showed that the as-prepared hybrid material possesses a synergistic peroxidase-like activity, and the ability to magnetic separation which can realize the recycle of catalysts. During the research, it has been found that the hybrid material has efficient catalytic activity towards the synthesis of phenazine pharmaceutical intermediates. Compared with traditional biological enzyme, it has higher catalytic efficiency, and the catalytic efficiency was retained as high as 88% after five consecutive used.