Design And Synthesis Of Novel Coumarin-Based Fluorescent Probes And Studies On Fluorescence Detection Of Reactive Sulfur Molecules

Fluorescence imaging technology has the advantages of high sensitivity,low biological toxicity,quick and easy operation,and rich information feedback.It plays an increasingly important role in the detection of reactive biological species,the research and controlled release of drugs,and the diagnosis and treatment of major diseases.Among them,due to the advantages of real-time visualization and non-invasiveness,organic dye-based fluorescent probes combined with fluorescence imaging technology have become one of the core tools of current research in chemistry.Reactive sulfur species（RSS）is a family of reactive sulfur-containing molecules,mainly including biological thiols（Cys,Hcy,GSH）,H₂S,SO₂,SO₃^2-,HSO₃^-,etc.,which play an important role in regulating many physiological processes.However,the abnormal level of its concentration has caused a bad impact on human health.In addition,coumarin fluorophores have the advantages of high quantum yield,low potential toxicity,high reproducibility of synthesis,and easy derivatization,which have great potential in the design and development of fluorescent probes for the detection of reactive sulfur species.Therefore,in this paper,a series of fluorescent probes were designed and synthesized based on coumarin for the detection of reactive sulfur molecules,and their detection mechanisms were studied in depth,and their applications in analytical sensing,environmental monitoring and bioimaging were discussed.The main work content is divided into the following parts for discussion:Chapter 1,the research background of fluorescence imaging technology is briefly described;the important role of reactive sulfur molecules in physiological processes and the adverse effects in the environment are introduced;the research status and future development directions of reactive sulfur molecular fluorescent probes based on coumarin fluorophores are reviewed.Chapter 2,a coumarin fluorescent probe that can specifically coordinate with Cu²⁺was designed and synthesized for the specific detection of H₂S in living cells.Compared with the H₂S probes that have been reported in the literature,the fluorescence probe has high quantum yield,low detection limit,fast reaction time,naked eye detection,and has great development potential in practical biological applications.Chapter 3,a bifunctional coumarin fluorescent probe with three reactive sites was designed and synthesized,which can not only realize the visual detection and quantitative analysis of H₂S in wastewater by combining fluorescent paper strips and smartphones（color identifier,Xiyi Technology）,showing potential application in the field of environmental detection,and can also perform low-concentration detection of GSH in living cells.Meanwhile,the differential detection mechanism of probe for H₂S/GSH was fully demonstrated by fluorescence spectra,UV absorption spectra,¹H NMR and DFT calculations.Chapter 4,the sensing strategy of the previous work combining fluorescent paper strips with a smartphone demonstrated its detection efficiency,but this still relies on hand-held UV lamps and dark environmental conditions.3D printing technology can quickly create highly complex integrated devices with various functions,which can solve the problems encountered above.Therefore,a bifunctional coumarin fluorescent probe with dual reactive sites was designed and synthesized,which can not only detect Cys in human serum quickly,intuitively,and in real time through a 3D-printed smartphone sensing platform,which is great important for the early detection of diseases,and can also observe the metabolic process of Cys in living cells through different excitation and emission channels.Chapter 5,in the process of detecting Cys metabolism,the interference of false positive signals may occur in the process of cell transmission,which affects the accuracy of test results.Photochromic probes have the ability to convert from one isomer（inert to the analyte）to the other（reactive to the analyte）when irradiated with ultraviolet（UV）and visible（Vis）light alternately,so as to achieve sensing accuracy by remote control and eliminate false positives.Therefore,a photochromic fluorescent probe based on two integrated mechanisms of ICT and FRET was developed to remotely monitor the metabolic process of Cys in living cells,which has certain practical value for the early and accurate diagnosis and precise treatment of cancer in clinic.Chapter 6,the full text is summarized.A series of coumarin fluorescent probes for detection of reactive sulfur molecules have been systematically developed in this paper,a photoluminescence sensing strategy is proposed,and multi-functional detection is realized,it provides new ideas and solutions for the development and design of the next generation of coumarin fluorophore-based reactive sulfur molecular fluorescence probes.