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The Construction And Performance Detection Of Small Molecular Probes For Quick-killing Chemical Agents

Posted on:2024-08-26Degree:MasterType:Thesis
Country:ChinaCandidate:X Y ZhangFull Text:PDF
GTID:2531307145460054Subject:Pharmacy
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Nerve agent and systemic agents are a type of highly reactive chemical agents that are colorless,transparent,weakly odorous,and possess strong toxicity with rapid onset of action.These agents,also known as quick-killing agents,can cause dysfunction of human organs shortly after entering the body.Upon entering the body,nerve agents bind to acetylcholinesterase(ACh E),inhibiting its activity and causing acetylcholine to accumulate in the synaptic cleft,which cannot be metabolized and inactivated normally.This accumulation results in severe disruption of the central and peripheral cholinergic nervous systems in the human body.The toxic effects of systemic agents are due to their binding with cytochrome oxidase in cells,which disrupts cellular oxidative metabolism and leads to adenosine triphosphate(ATP)deficiency,causing cellular metabolic disorders,tissue hypoxia,systemic dysfunction,and ultimately,systemic poisoning.These agents have been used as chemical warfare agents and pose a significant threat to public safety.Small molecule probe technology offers several advantages,including high selectivity,sensitivity,ease of use,and low cost,and has found broad applications in fields such as physical chemistry,drug analysis,environmental monitoring,and biomedical research.This study focuses on the design,synthesis,and screening of several highly sensitive,specific,and fast-reacting colorimetric/fluorescent probes for the detection and diagnosis of two quick-killing agents: nerve agents and systemic agents(cyanide).The study aims to provide reliable technical support for rapid on-site detection and diagnosis of lethal toxins,as well as targeted poisoning treatment.The specific research contents are as follows:Based on the self-built compound library,two colorimetric probes named Z1 and Z2 were screened out to detect nerve agent.In the ultraviolet spectrum experiment,the maximum absorption wavelengths of Z1 and Z2 were 424 nm and 446 nm,respectively.After the addition of nerve agent mimics,the maximum absorption wavelengths of Z1 and Z2 were red shifted to 556 nm and 542 nm respectively,accompanied by significant color changes within 3 s,which could be recognized by naked eye,and the reaction can be fully completed within 2 min.The recovery experiments showed that the probes Z1 and Z2 could detect nerve agents quantitatively and the limit of detection of Z1 for nerve agent was 0.57 μmol/L.Z1 was prepared into test paper for rapid on-site detection of nerve agent.Compared with standard test paper FZZ01,the test paper of Z1 showed obvious advantages of high sensitivity and significant discoloration.Two fluorescent probes,NMU-1 and NMU-2,were designed and synthesized for the selective detection of nerve agents,among which NMU-1 exhibited excellent detection performance.As the concentration of nerve agents increased,the fluorescence signal of NMU-1 at 498 nm gradually weakened,and the fluorescence intensity showed a good linear relationship with the concentration of the nerve agent.NMU-1 has a low LOD(4.60 μmol/L),a fast response time(3 min),and a large Stokes shift(98 nm),accompanied by a significant color change.Due to its high sensitivity and good selectivity,NMU-1 has been successfully applied for imaging nerve agents in PC12 cells.Furthermore,NMU-1 was used as a key component in the development of a chemical warfare agent detection test paper.After contact with nerve agents,the test paper exhibited obvious fluorescence changes under handheld 365 nm ultraviolet light.Six dual-functional probes were designed and synthesized for the simultaneous detection of nerve agents and cyanide.Fluorescence spectroscopy experiments showed that probes D2,D4,and D5 exhibited at least a 200-fold increase in fluorescence intensity at around 440 nm,while probes D6 and D9 showed an increase in fluorescence intensity at around 470 nm upon reaction with nerve agents.Further experiments revealed that probes D6 and D9 exhibited significant linear relationships(R2D6=0.9941,R2D9=0.9946)between fluorescence intensity and cyanide concentration at 597 nm and 596 nm,respectively,with detection limits of 0.38 μmol/L and 0.96 μmol/L,respectively.In terms of reaction time,probe D9 exhibited a slower reaction rate with cyanide,while probe D6 showed a fast response,with a significant increase in fluorescence intensity within 1 min.Thus,we successfully developed and screened a dual-functional fluorescent probe D6,which showed good detection performance for both nerve agents and cyanide,and has promising applications in environmental protection and public safety.
Keywords/Search Tags:Nerve agents, cyanide, fluorescent probe, colorimetric probe
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