Construction Of Ratiometric Molecularly Imprinted Electrochemical Sensors Based On Metal Complexes And Their Application In Psychotropic Drugs Detection

In recent years,electrochemical analysis methods have been widely used in clinical and field monitoring of because of its advantages of simple preparation,low cost,rapid response and portable instrument.However,due to the lack of specific recognition in the classical electrochemical sensors,the target analytes could be difficult to accurately quantify from structural analogues with similar electrooxidation mechanism.In addition,it was necessary to further eliminate the internal and environmental interference,that is,to improve the anti-interference ability of the sensor and to directly detect target drugs in complex biological samples.In order to solve the above problems,this thesis combined the two strategies of molecular imprinting and ratiometric sensing to enhance the electrochemical performance of the sensors.The purpose of this thesis was to develop more sensitive,simple and accurate quantitative analysis methods for psychotropic drugs.The details were as follows:（1）A ratiometric molecularly imprinted electrochemical sensor based on poly（methylene blue）for the chlorpromazine hydrochloride detectionIn this work,a novel ratiometric electrochemical sensor for the selective detection of chlorpromazine（CPZ）was developed.The sensor was constructed by electrodepositing dual-monomer molecularly imprinted polymer（DMMIP）film on the surface of Pt/Co₃O₄ nanoparticles modified glassy carbon electrode,using CPZ as template molecule,methylene blue and catechol as functional monomers.The quantitative detection of CPZ was performed by differential pulse voltammetry,using the peak current of poly（methylene blue）as reference signal and the peak current of CPZ as indicating signal.Under the optimal conditions,the ratiometric signal was linear to CPZ concentration in the range of 0.005–9μmol L^-1（R²=0.9962）,and the limit of detection was 2.6 nmol L^-1.Moreover,the ratiometric sensor showed high reproducibility,stability and applicability towards CPZ detection.（2）A ratiometric electrochemical sensor based on Cu-coordinated molecularly imprinted polymer for detection of perphenazineHere,a new metal-chelated monomer Cu-coordinated pyrrolio-3-carboxylate（Cu-Py COOH）was synthesized,and a novel electrochemical sensor was constructed by electrodepositing Cu-coordinated molecularly imprinted polymer on Ag nanoparticles（NPs）modified flexible porous carbon cloth.Under the optimum conditions,the quantitative detection of PPZ was performed with differential pulse voltammetry.It was found that the peak current ratio of PPZ and Ag NP was linear to the concentration of PPZ in the range of 1–700 nmol L^-1（R²=0.9968）,and the limit of detection was0.43 nmol L^-1（S/N=3）.Here,the ratiometric strategy corrected the electrode area error caused by cutting carbon cloth manually,so that the resulted sensor displayed satisfactory reproducibility and anti-interference ability.The practicability of the sensor was examined by determining human serum and pharmaceutical samples,and satisfactory results were achieved.（3）A ratiometric electrochemical sensing platform based on multifunctional molecularly imprinted polymer with F-N active sitesIn this work,Fe coordination aminophenanthroline（Fe-AP）was synthesized as a new multifunctional monomer,and an MIP film with Fe-N active catalytic sites（Fe-DMMIP）was designed and prepared.The Fe-DMMIP sensor was constructed by electrodeposition of Fe-coordinated aminophenanthroline and 3,4-ethylenedioxythiophene on N,S co-doped carbon material,using cannabinoid（CBD）as template molecule.Under the optimal conditions,the ratiometric signal was linear to CBD concentration in the range of 0.004-0.8μmol L^-1（R²=0.9946）with a detection limit of 2.9 nmol L^-1.In addition,through replacing the template molecule,the resulting biomimetic sensor also exhibits good performance in sensing other psychoactive substances such as melatonin and 5-hydroxytryptophan,with LODs of 19 nmol L^-1 and8.0 nmol L^-1for them,respectively.（4）Molecular imprinting electrochemical sensor based on metal-chelating imprinting process for specific recognition and ratiometric detection of lidocaineHere,a novel ratiometric MIP electrochemical sensor based on metal coordination interactions was prepared by using Cu coordination 1-vinylimidazole（Cu-Vim）as monomer,and used for specific recognition and ratiometric detection of lidocaine（LC）.Here,N,S co-doped carbon material was also used in this work,and its precursor was discarded orange peel.This biomass derived carbon material was environmentally friendly.Thus,the resulted sensor not only displayed high selectivity and sensitivity,but also exhibited satisfactory reproducibility and anti-interference ability.It was found that the peak current ratio of LC and Cu（Ⅰ）was linear to the concentration of LC in the range of 0.008–2.5μmol L^-1（R²=0.9951）,and the limit of detection was 1.9 nmol L^-1（S/N=3）.The practicability of the sensor was examined by determining human serum and pharmaceutical samples,and satisfactory results were achieved.（5）Metal coordination-assisted dual template orderly imprinted electrochemical sensor for ratiometric and simultaneous sensing of imipramine and 5-hydroxytryptophanIn this work,a dual-template imprinting electrochemical sensor was designed with metal ion as pivot.When using this the Cu coordination 4-（2-pyridylazo）-resorcinol monomer（Cu-PAR）monomer for electropolymerization,a Cu coordination double-template MIP（Cu-DTMIP）was successfully synthesized on the surface of the sensor,which modified with Ag NPs as the internal reference substance.Under the optimum conditions,it could be successfully used for simultaneous sensing of two psychotropic drugs,5-hydroxytryptophan（5-HTP）and imipramine（IM）.Moreover,it was applied to detect 5-HTP and IM in serum and pharmaceutical samples,and satisfactory results were achieved.