Application Of Metal-organic Frameworks And Their Derivatives-based Electrochemical Sensors In Pharmaceutical Detection

As a research area of analytical chemistry,pharmaceutical detection is of significance in the fields of pharmacy quality control,pharmaceutical development and pharmacokinetics research,environmental monitoring,food safety and so on.At present,among various detection methods,electrochemical sensor becomes a research focus due to its merits of simple operation,fast response and easy on-line analysis.For electrochemical sensor,developing novel and efficiency electrode modify materials is crucial to improve the feature of electrochemical sensor.Metal-organic frameworks(MOFs)are suitable to be an electrode modify materials owing to their high specific surface area,high porosity,abundant active sites and etc.However,the conductivity and redox-activity of most MOFs are poor,and the way to prepare the MOFs-based sensors is not complete.Therefore,these disadvantages of MOFs confine their application in electrochemical sensor.To improve the conductivity and the redox-activity of most MOFs,as well as the way to construct the sensors,we combine electrochemical technic with MOFs nanomaterial.On one hand,developing new and superior MOFs derivatives-based electrochemical sensors via diverse derivatization or electrode modify approaches,where introducing the nanomaterials with high conductivity,containing acetylene black(AB),gold nanoparticles(Au NPs)and 3-Thiophenemalonic acid(3-TPA),to counple with MOFs or carbonized MOFs.On the other hand,constructing novel and excellent MOFs-based electrochemical sensor through mixed-metals-cathodic reduction electrosynthesis.According to whether the electrode modify process involves binder,the proposed electrochemical sensors can be classified into two types(binder and binder-free).Besides,research contents also contains the investigation on the electrochemical performance and action mechanism of the target pharmaceutical molecules on the electrodes,conditions optimization,assessment of sensors' selectivity,reproducibility and stability and setting up the detection method for real samples.The detailed research contents and results are as follows:1.ZIF-8-AB compound modify glassy carbon electrode(GCE)for rutin detection.AB,which has high conductivity,was combined with ZIF-8 synthesized via solvothermal to be a compound by physical mix strategy,then ZIF-8-AB/GCE is fabricated using the compound with the help of chitosan binder by drop-casting.Physical characterization demonstrates ZIF-8 and AB have been mixed uniformly.Cyclic voltammetry(CV)and electrochemical impedance spectroscopy(EIS)suggest the sensor displays an excellent electrocatalytic activity,which possible ascribed to the combined action between ZIF-8 and AB.Under the optimized condation,the linear range is from 0.1 to 10 ?M,the Limit of detection(LOD)is 0.004 ?M,and the sensor can detect rutin in pharmacy tablets sensitively.2.Co-N doped carbon nanotube hollow polyhedron(Co-NCNHP)derived from core-shell ZIF-8@ZIF-67 coupled Au NPs for voltammetric sensing of acetaminophen.With ZIF-8 being the seeds,a core shell ZIF-8@ZIF-67 nanomaterial is prepared.Co-NCNHP is synthesized from ZIF-8@ZIF-67 by solvothermal-pyrolysis strategy.Comparison study is carried out on the physical property and electrochemical activity of the three kinds of MOFs(carbonized-ZIF-8,carbonized-ZIF-67 and Co-NCNHP).Then Au NPs/Co-NCNHP/GCE is constructed for sensing acetaminophen with the help of chitosan binder through drop-casting and electrodeposition.Comparison study demonstrates Co-NCNHP possesses better sensitivity and stability,owing to the high specific surface area and abundant of Co,N and CNTs.Au NPs/Co-NCNHP/GCE exhibits excellent electrochemical performance,the linear range is 0.1-40 ?M?40-250?M,LOD of 0.05 ?M,and successfully determination of acetaminophen in pharmacy tablets and spiked urine with high sensitivity and good selectivity.3.Fabrication of Co-NCNHP/3-TPA/GCE for monitoring metronidazole.To avoid the effect of binder on the performance of electrode modifer,Co-NCNHP/3-TPA/GCE withou binder is prepared by two-step electropolymerization.Physical characterization proves 3-TPA and Co-NCNHP have been polymerized onto GCE surface.CV and EIS suggest Co-NCNHP/3-TPA owns the most excellent electrochemical activity and is faveriable to the reduction reaction of metronidazole.The sensor,which pocesses good selectivity and long-term stability,has a linear reponse to metronidazole from 0.1 to 20?M,20 to 800 ?M with LOD of 0.024 ?M,and has been used to detect metronidazole efficiently in spiked lake and urine samples.4.In-situ electrodeposition porous and binder-free Co-doped Ni-MOF(Co/Ni-MOF)film for electrochemical determination of levofloxacin.To further simplify the the preparation of electrodes,we design porous and binder-free Co/Ni-MOF/GCE via mixed metals-cathodic reduction electrodeposition.Physical characterization proves that the synthesized MOFs is Ni-MOF with partly Ni2+replaced by Co2+.CV and EIS reveal that Co/Ni-MOF has excellent electrochemical activity in the oxidation of levofloxacin.The reason is probable that the couple of Co and Ni improves the conductivity.Especially,the Co/Ni-MOF/GCE has good sensitivity and stability,and its linear response to levofloxacin is in range of 0.1-500 ?M with LOD of 0.022 ?M,as well as detect of levofloxacin in eye drop and spiked milk with high efficiency.To sum up,research results reveal that the four types of MOFs-based and MOFs derivatives-based electrochemical sensors exhibit electrochemical activity to rutin,acetaminophen,metronidazole and levofloxacin respectively,and the sensors can be utilized to monitor the target pharmaceutical molecules with high selectivity and high sensitivity.Particulary,the prepared electrochemical sensors of binder-free is endowed with the strong long-term stability.This paper provides a new approach for determination of pharmaceutical molecules mentioned above,and opens a new way to the MOFs'application in electrochemical sensor as well.