Nanoassembly,biomimetic Catalysis And Biosensing Of Metal-organic Framework Composites

Metal-organic frameworks(MOFs),also known as porous coordination polymers(PCPs)or porous coordination network structure are a class of crystallized porous polymeric materials formed by the coordination of metal ions/clusters and organic bridging ligands.Compared with conventional zeolites and other inorganic porous materials,MOFs show high internal surface area,tunable pores,relatively stable skeleton structure,permanent channel and special physical and chemical properties.MOFs play a crucial role in optics,magnetics,electrical,catalysis and sensing.To date,the biological analytical technology based on the MOFs has been used in gas sensing,cell imaging and in vivo treatment,which has became one of the research hotspots in life analytical community.This thesis focuses on the nanoassembly and biomemetic properties of MOF,and the construction of biosensor and analysis method for detection of biomolecule.The main works are described as follows:1.Porphyrin functionalized porous carbon derived from metal-organic framework as a biomimetic catalyst for electrochemical biosensingIn this work,a kind of biomimetic catalyst was designed as a signal probe by the assembly of porphyrin on porous carbon(PC)derived from metal-organic frameworks for electrochemical biosensing.First,PC was prepared by direct carbonization of a zeolite-type metal-organic framework as both a precursor and a template,and characterized by transmission electron microscopy,nitrogen sorption isotherm,X-ray photoelectron spectroscopy and X-ray diffraction.Then the PC was non-covalently functionalized with iron(?)meso-5,10,15,20-tetrakis(4 carboxyphenyl)porphyrin chloride(FeTCPP)via non-covalent interactions.The resulting nanocomposite of PC/FeTCPP possesses an excellent electrocatalytic activity toward oxygen reduction.Coupling with the enzymatic catalysis of glucose oxidase,a glucose biosensor was constructed on the basis of O2 consumption.The biomimetic sensor enables a reliable and sensitive determination of glucose with a linear range of 0.5 to 18 mM and a detection limit of 0.08 mM at a signal-to-noise ratio of 3.Moreover,the biosensor exhibits the analytical reproducibility and stability with a lower relative standard deviation of 4.2%.In an application to detect glucose in human serum samples,this glucose biosensor had good detection accuracy with analytical recoveries from 97.3%to 107.7%.Therefore,the porphyrin functionalized PC provides a promising biomimetic platform for constructing the biosensors,and has potential application in bioanalysis and clinical diagnosis.2.Porphyrin-encapsulated metal-organic frameworks as mimetic catalysts for electrochemical DNA sensing via allosteric switch of hairpin DNAA sensitive electrochemical sensor is designed for DNA detection based on mimetic catalysis of metal-organic framework(MOF)and allosteric switch of hairpin DNA.The functional MOFs are synthesized as signal probes by a one-pot encapsulation of iron(?)meso-5,10,15,20-tetrakis(4-carboxyphenyl)porphyrin chloride(FeTCPP)into a prototypal MOF,HKUST-1(Cu),and sequentially conjugated with streptavidin(SA)as a recognition element.The resulting FeTCPP@MOF composites can mimetically catalyze the oxidation of o-phenylenediamine(o-PD)to 2,2'-diaminoazobenzene,which is a good electrochemical indicator for signal readout.The presence of target DNA introduces the allosteric switch of hairpin DNA to form SA aptamer,and thus,FeTCPP@MOF-SA probe is brought on the electrode surface via the specific recognition between SA and the corresponding aptamer,resulting in the enhancement of electrochemical signal.The "signal-on" electrochemical sensor can detect target DNA down to 0.48 fM with the linear range of 10 fM to 10 nM.Moreover,the MOF-based electrochemical sensor exhibits acceptable selectivity against even a single mismatched DNA and good feasibility in complex serum matrixes.This strategy opens up a new direction of porphyrin-functionalized MOF for signal transduction in electrochemical biosensing stability.3.Porphyrinic metal-organic framework as electrochemical probe for DNA sensing via triple-helix molecular switchAn electrochemical DNA sensor was developed based on the electrocatalysis of porphyrinic metal-organic framework(MOF)and triple-helix molecular switch for signal transduction.The streptavidin functionalized zirconium-porphyrin MOF(PCN-222@SA)was prepared as signal nanoprobe via covalent method and demonstrated high electrocatalysis for O2 reduction.Due to the large steric effect,the designed nanoprobe was blocked for the interaction with the biotin labeled triple-helix immobilized on the surface of glassy carbon electrode.In the presence of target DNA,the assistant DNA in triple-helix will hybridize with target DNA,resulting in the disassembly of triple-helix molecular.Consequently,the end biotin away from the electrode was "activated" for easy access to the signal nanoprobe,PCN-222@SA,on the basis of biotin-streptavidin biorecognition.The introduction of signal nanoprobe to a sensor surface led to a significantly amplified electrocatalytic current towards oxygen reduction.Integrating with DNA recycling amplification of Exonuclease ?,the sensitivity of the biosensor was improved significantly with detection limit of 0.29 fM.Moreover,the present method has been successfully applied to detect DNA in complex serum matrix.This porphyrinic MOF-based strategy has promising application in the determination of various analytes for signal transduction and has great potential in bioassays.4.Platinum nanoparticles encapsulated metal-organic frameworks for the electrochemical detection of telomerase activityA simple and rapid electrochemical sensor is constructed for the detection of telomerase activity based on the electrocatalysis of platinum nanoparticle(PtNP)encapsulated metal-organic frameworks(MOFs),which are synthesized by one-pot encapsulation of PtNPs into prototypal MOFs,UiO-66-NH2.The capture DNA(cDNA)functionalized MOF was prepared as signal nanoprobe via covalent method.A telomerase primer(TS),which could be extended in the presence of telomerase and dNTPs,was attached onto a glassy carbon electrode(GCE).After the telomerase primer was extended,the Pt@UiO-66-NH2-cDNA probe could form a hybrid with the extended part on the sensor surface.Integrating with the efficient electrocatalysis of Pt@MOFs towards NaBH4 oxidation,this biosensor shows the wide dynamic correlation of telomerase activity from 5×102 to 107 HeLa cells mL-1 and the telomerase activity in a single HeLa cell was calculated to be 2.0×10-11 IU,providing a powerful platform for detecting telomerase activity.5.Nanoscaled porphyrinic metal-organic frameworks for electrochemical detection of telomerase activity via telomerase triggered conformation switchIn this work,we developed a nanoscaled porphyrinic metal-organic framework(PorMOF)with iron porphyrin as linker and Zirconium ions as node for electrochemical detection of telomerase activity.The as-prepared PorMOF was characterized with powder X-ray diffraction,scanning electron microscopy and spectroscopic techniques,and demonstrated the excellent electrocatalytic activity towards O2 reduction.Sequentially,the functionalization of PorMOF with streptavidin results in water-stable electrochemical tracer for detection of telomerase.Upon the telomerase-triggered extension,the assistant DNA 1(aDNAl)-assistant DNA 2(aDNA2)duplex could switch into a hairpin structure,and thus the aDNA2 could be released and then hybridize with the capture DNA.Therefore,the PorMOF@SA tracer could be introduced on the electrode surface via biotin-streptavidin recognition,resulting in the strong electrochemical signal for readout.The developed approach displayed desirable dynamic range and limitation of detection down to 30 Hela cells mL-1.The telomerase activity in single HeLa cell was calculated to be 2.2×10-11 IU with good reproducibility and stability.The nanoscaled porphyrinic MOF provided a powerful platform for electrochemical signal transduction and had the promising application in the determination of biomolecules for clinical application.6.Bifunctional metal-organic frameworks as self-controlled catalysis and indicator of nitric oxideThe imaging of nitric oxide(NO)and its donors is crucial to explore NO-related physiological and pathological processes.In this work,we demonstrate the use of Cu-based metal organic frameworks(Cu-MOF)as a catalyst for the generation of NO from the biologically occurring substrate,S-nitrosothiols(RSNOs).The Cu-MOF catalyst was confirmed by powder X-ray diffraction to remain structurally intact in aqueous environments.The paramagnetic Cu2+in the MOF could quench the luminescence of triphenylamine,Cu-MOF only exhibited weak emission at 450 nm.Upon the addition of NO and RSNOs,the luminescence was recovered directly.More significantly,the Cu-MOF can react with three kinds of RSNOs to generate NO,and thus the catalysis is inhibited,as noted as self-controlled process.The Cu-MOF also led to its successful application in the biological imaging of NO in living cells.The bifunctional MOFs not only offer a novel platform for real-time monitoring NO species but also remarkably improve the methodologies to elucidate the NO-related biological processes.