Selenide-based electrocatalytic sensors for sensitive peroxynitrite detection in biological media: a bottom-up approach for functional interface design

用于生物介质中敏感过氧亚硝酸盐检测的硒化物电催化传感器：功能界面设计的自下而上方法

• 批准号: 10203223
• 负责人: MEKKI BAYACHOU
• 金额: $ 44.71万
• 依托单位: CLEVELAND STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10203223
• 关键词: Address; Adult; Affect; American Heart Association; Antioxidants; Apoptosis; Behavior; Biochemical; Biological; Cardiovascular Diseases; Cell Death Induction; Cell membrane; Cell physiology; Cessation of life; Chemicals; Chronic; Clinical; Complex; Coupled; DNA; Data; Detection; Development; Disease; Electrodes; Electron Spin Resonance Spectroscopy; Evaluation; Film; Fluorescent Probes; Functional disorder; Goals; Illusions; Immune response; Immunohistochemistry; In Situ; Inflammation; Libraries; Light; Link; Lipids; Masks; Measurement; Measures; Mediating; Methods; Molecular; Monitor; Morbidity - disease rate; Natural graphite; Necrosis; Nitric Oxide; Organoselenium Compounds; Oxidation-Reduction; Paper; Pathologic; Pathology; Pathway interactions; Performance; Peroxonitrite; Pharmaceutical Chemistry; Physiological; Physiological Processes; Play; Process; Property; Proteins; PubMed; Publishing; Reaction; Reporting; Role; Selenium; Sepsis; Signal Transduction; Superoxides; Surface; Techniques; Testing; Thinness; Time; United States; Work; analytical method; assault; base; biological systems; carbon fiber; cytotoxic; design; detection method; in vivo; innovation; microsensor; miniaturize; mortality; mortality statistics; nitration; oxidation; sensor; statistics; stress reactivity; tool

Project Summary: Background and Challenge: Peroxynitrite (OONO-) emerged as a potent cytotoxic compound and has been implicated in a host of pathophysiological conditions. Peroxynitrite is the primary product of the in vivo reaction of nitric oxide and superoxide anion-radical. The multifaceted physiologic reactions of this compound are directly implicated in a number of pathologies including cardiovascular disease, immune response, chronic inflammation, and sepsis, to cite a few. According to recent statistics by the American Heart Association, just cardiovascular disease alone claims about 7 deaths every 4 minutes. On the other hand, sepsis affects 1.7 million adults in the United States each year and potentially contributes to more than 250,000 deaths. Just these two statistics are staggering and make the footprint of this deadly biological analyte an important priority. The common thread that links peroxynitrite to all cited pathologies is its potent reactivity toward most cellular components including DNA, proteins, and lipids in cell membranes. Substantial oxidations and other transformations of proteins, DNA, and lipids contribute to the disruption of key cellular functions. Assessing peroxynitrite’s deleterious effects and examining hypotheses of its potential signaling roles cannot be achieved without first accurately measuring and monitoring its concentration. This task is however inherently difficult due to low submicromolar concentrations under physiologic conditions coupled with its high reactivity. Sensitive and accurate measurement of peroxynitrite is crucial in order to shed light on the illusive pathophysiologic roles of this metabolite. Some of the known detection methods for peroxynitrite include oxidation of fluorescent probes, EPR spectroscopy, chemiluminescence, immunohistochemistry, and probe nitration; however, these are more difficult to apply for real-time quantification due to their inherent complexity. The electrochemical detection of peroxynitrite is a simpler and more convenient technique for application in biological settings. However, a systematic development of the right electrode interface that enhances the sensitivity and selectivity for this molecule is lacking. Recently, several synthetic organic selenides have been prepared as antioxidants in medicinal chemistry. Electrochemical data in our hands showed that some organoselenium compounds have specific redox activity with peroxynitrite in solution. For these reasons, we believe that an electrode interface decorated with organoselenides attached to the surface will potentially serve as catalytic entities for mediated PON electrocatalytic determination. Our proposal: In this work, we propose to develop a functional thin film material based on defined organic selenides chemically attached on graphite electrodes and use this interface in sensitive electrochemical determination of peroxynitrite. This bottom-up interface design approach is innovative because it allows us to design an electrocatalytic interface for the detection and determination of peroxynitrite driven by molecular and electronic properties of the organic selenides used. This is driven by the overall hypothesis that the redox-rich organoselenium compounds will allow us to use them as active redox catalytic centers tethered to the electrode surface to electrocatalytically measure PON in solution. The work will pursue three specific aims including: 1) developing a selenide-decorated electrode for PON determination using a reference compound, followed by 2) generating a library of selenides with varying substituents on the selenium catalytic center and test the catalytic properties of the resulting modified interface towards PON determination; and finally 3) miniaturizing the best performing catalytic interfaces by transferring the process to ultramicroelectrodes (carbon fiber) to prepare a single-body PON microsensor for use under biological settings. Significance: The successful development of a reliable PON microsensor will not only enable in-situ measurement of this reactive stress marker under biological setting but will also shed light on obscure mechanisms through which this potent species operates under many disease states.

项目摘要： 背景和挑战：过氧亚硝酸盐（OONO-）作为潜在的细胞毒性化合物和 在许多病理生理状况中隐含。过氧亚硝酸盐是 一氧化氮和超氧化阴离子 - 自由基的体内反应。这是多方面的生理反应 化合物直接与许多病理有关，包括心血管疾病，免疫疾病 反应，慢性炎症和败血症引用一些。根据美国人的最新统计数据 心脏协会，仅心血管疾病就会声称每4分钟死亡约7人。另一方面 手，败血症每年在美国影响170万成年人，并有助于更多 超过25万人死亡。只是这两个统计数字令人惊讶，并使这个致命的足迹成为了 生物分析物是重要的优先级。将过氧亚硝酸盐与所有引用的病理联系起来的共同线程 它是对大多数细胞成分的潜在反应性，包括细胞中的DNA，蛋白质和脂质 膜。蛋白质，DNA和脂质的大量氧化和其他转化有助于 关键细胞函数的破坏。 评估过氧亚硝酸盐的有害作用并检查其潜在信号传导作用的假设 如果没有先准确测量和监视其浓度，就无法实现。这个任务是 但是，由于生理条件下的亚微摩尔浓度较低，因此本质上很难 具有高反应性。对过氧亚硝酸盐的敏感，准确的测量对于散发光至关重要 在该代谢产物的说明性病理生理作用上。一些已知的检测方法 过氧亚硝酸盐包括荧光探针的氧化，EPR光谱，化学发光， 免疫组织化学和探针硝化；但是，这些更难实时申请 由于其继承的复杂性而导致的量化。过氧亚硝酸盐的电化学检测更简单 以及在生物环境中应用的更方便的技术。但是，系统发展 缺乏提高对该分子的灵敏度和选择性的右电极界面。 最近，已经制备了几种合成有机硒，作为医学化学中的抗氧化剂。 我们手中的电化学数据表明，某些有机凝胶化合物具有特定的氧化还原 在溶液中用过氧亚硝酸盐的活性。由于这些原因，我们认为电极界面装饰 随着有机苯甲酸的附着在表面上 电催化测定。 我们的建议：在这项工作中，我们建议开发基于定义的功能性薄膜材料 化学连接在石墨电极上的有机硒，并在敏感的 过氧亚硝酸盐的电化学测定。这种自下而上的界面设计方法是创新的 因为它允许我们设计一个电催化界面，以检测和确定 通过使用有机硒化的分子和电子特性驱动的过氧亚硝酸盐。这是由 总体假设富含氧化还原的有机凝胶化合物将使我们能够将它们用作活跃 氧化还原催化中心将电极表面拴在溶液中的电催化中。 这项工作将追求三个特定目标，包括：1）为PON开发硒化的电极 使用参考化合物的确定，然后是2）生成具有变化的硒库 硒催化中心上的亚探测器，并测试所得修饰的催化特性 pon测定的接口；最后3）小型性能最佳性能催化界面 通过将工艺转移到超大型电极（碳纤维）中以制备单体PON 在生物环境下使用的微型传感器。意义：可靠的成功发展 PON微型传感器不仅将在生物学下实现该反应应力标记的原位测量 设置，但还将阐明这种有效物种在下面运作的晦涩的机制 许多疾病状态。