1,2-Dioxetanes for Quantitative Chemiluminescence Imaging

用于定量化学发光成像的 1,2-二氧杂环丁烷

• 批准号: 2155170
• 负责人: Alexander Lippert
• 金额: $ 50万
• 依托单位: Southern Methodist University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2155170&HistoricalAwards=false
• 关键词: Dioxetanes; Quantitative; Chemiluminescence; Imaging

With the support of the Chemical Structure, Dynamics, and Mechanisms B (CSDM-B) Program in the Division of Chemistry, Professor Alexander R. Lippert of Southern Methodist University is studying the fundamental structures and mechanisms of chemiluminescent molecules for use in quantitative chemiluminescence imaging techniques. Chemiluminescence is the light observed in fireflies and glowsticks and is sometimes referred to as cold light generated during a chemical reaction. Imaging in cells and mammals using chemiluminescence offers significant advantages including low-cost, high sensitivity, low phototoxicity, and the ability to image in deeper tissue. This emerging technique for molecular imaging is limited, however, by a lack of methods for precise quantitative imaging of analytes and optimal microscopy instrumentation. The proposed study will advance the field of chemiluminescence sensing by progressing from rough relative measurements to precise quantitative imaging of a diverse set of analytes. This project will also serve to enhance participation of under-represented students in STEM. In collaboration with a local HBCU Prairie View A&M University, the PI will recruit and co-mentor under-represented students to participate in this research and receive long-term mentorship.The three specific aims of the project are: (1) develop near-infrared (NIR) and short-wave infrared (SWIR) ratiometric chemiluminescent probes for quantitative Imaging; (2) develop kinetics-based chemiluminescence probes for quantitative imaging; (3) develop chemiluminescence microscopy for quantitative imaging. The proposed work aims to gain mechanistic understanding to develop innovative molecules, instrumentation, and methods for quantitative chemiluminescence imaging of O2, pH, metals, reactive species, and enzymes in cells and animals, thereby advancing fundamental understanding of chemiluminescence and broadly enabling biological studies. Chemiluminescent molecules with NIR and SWIR ratiometric emission will provide better quantification and the ability to image in deeper tissue. The kinetics of the chemiluminescent reactions and reactions of probes with analytes will be solved in detail and methods will be developed to advance this understanding in the context of chemiluminescence microscopy. New types of chemiluminescence microscopes will be developed with optical components that maximize light gathering ability and minimize photon loss. Finally, the translation of novel molecules and mechanistic understanding into methods for cellular and whole animal imaging will unlock a new field of high sensitivity, low phototoxicity, and deep tissue quantitative chemiluminescence imaging.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

在化学结构，动力学和机制B（CSDM-B）计划的支持下，南方卫理公会大学的Alexander R. Lippert教授正在研究用于定量化学化学成像化学化学发光分子的基本结构和机制技术。化学发光是在萤火虫和发光棒中观察到的光，有时也称为化学反应过程中产生的冷光。使用化学发光的细胞和哺乳动物成像具有显着优势，包括低成本，高灵敏度，低光毒性以及在更深的组织中形象的能力。然而，由于缺乏用于精确定量成像和最佳显微镜仪器的方法，这种用于分子成像的新兴技术受到限制。拟议的研究将通过从粗糙的相对测量到一组各种分析物的精确定量成像来推进化学发光传感的领域。该项目还将有助于增强代表性不足的学生参与STEM。与当地的HBCU草原观点A＆M大学合作，PI将招募和同事不足的学生参与这项研究并获得长期指导。该项目的三个具体目标是：（1）近乎发展。红外（NIR）和短波红外（SWIR）比率化学发光探针进行定量成像； （2）开发基于动力学的化学发光探针进行定量成像； （3）开发化学发光显微镜进行定量成像。拟议的工作旨在获得机械理解，以开发创新的分子，仪器和方法，用于对细胞和动物的O2，pH，金属，反应性物种和酶进行定量化学发光成像，从而促进对化学发光的基本理解并广泛实现生物学研究。具有NIR和SWIR比率发射的化学发光分子将提供更好的定量和在更深的组织中形象的能力。化学发光反应的动力学和探针与分析物的反应将详细介绍，并将开发方法，以在化学发光显微镜的背景下提高这种理解。新型的化学发光显微镜将使用光学成分开发，从而最大化光收集能力并最大程度地减少光子损失。最后，将新分子和机械理解转化为细胞和整个动物成像的方法将释放一个高灵敏度，低光毒性和深层组织定量化学发光成像的新领域。这反映了NSF的法规任务，并被认为值得支持的支持。通过使用基金会的智力优点和更广泛影响的评论标准进行评估。

项目成果

Exploring the Structural Space of Chemiluminescent 1,2-Dioxetanes

• DOI: 10.1021/acssensors.2c02371
• 发表时间: 2022-12-27
• 期刊: ACS SENSORS
• 影响因子: 8.9
• 作者: Haris, Uroob;Lippert, Alexander R.
• 通讯作者: Lippert, Alexander R.

Oxygen‐Sensing Chemiluminescent Iridium(III) 1,2‐Dioxetanes: Unusual Coordination and Activity

氧气 - 传感化学发光铱 (III) 1,2 - 二氧杂环丁烷：不寻常的配位和活性

• DOI: 10.1002/anse.202200085
• 发表时间: 2022
• 期刊: Analysis & Sensing
• 作者: Kagalwala, Husain N.;Bueno, Lorena;Wanniarachchi, Hashini;Unruh, Daniel K.;Hamal, Khagendra B.;Pavlich, Cyprian I.;Carlson, Graham J.;Pinney, Kevin G.;Mason, Ralph P.;Lippert, Alexander R.
• 通讯作者: Lippert, Alexander R.