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.

在化学系化学结构、动力学和机制B（CSDM-B）项目的支持下，南卫理公会大学Alexander R. Lippert教授正在研究用于定量化学发光成像的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荧光棒中观察到的光，有时被称为化学反应过程中产生的冷光。使用化学发光对细胞和哺乳动物进行成像具有显着的优势，包括低成本、高灵敏度、低光毒性以及能够在更深的组织中成像。然而，由于缺乏对分析物进行精确定量成像的方法和最佳显微镜仪器，这种新兴的分子成像技术受到限制。拟议的研究将从粗略的相对测量发展到对多种分析物的精确定量成像，从而推动化学发光传感领域的发展。该项目还将有助于提高代表性不足的学生对 STEM 的参与。 PI 将与当地 HBCU Prairie View A&M 大学合作，招募并共同指导代表性不足的学生参与这项研究并接受长期指导。该项目的三个具体目标是：(1) 发展近期用于定量成像的红外 (NIR) 和短波红外 (SWIR) 比率化学发光探针； (2) 开发基于动力学的化学发光探针进行定量成像； (3)开发用于定量成像的化学发光显微镜。拟议的工作旨在获得机理理解，以开发用于细胞和动物中 O2、pH、金属、活性物质和酶的定量化学发光成像的创新分子、仪器和方法，从而增进对化学发光的基本理解并广泛促进生物学研究。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组织中成像的能力。将详细解决化学发光反应和探针与分析物反应的动力学，并开发方法以在化学发光显微镜的背景下推进这种理解。将开发新型化学发光显微镜，其光学元件可最大限度地提高集光能力并最大限度地减少光子损失。最后，将新分子和机制理解转化为细胞和整体动物成像方法将开启高灵敏度、低光毒性和深层组织定量化学发光成像的新领域。该奖项反映了 NSF 的法定使命，并被认为值得支持通过使用基金会的智力优点和更广泛的影响审查标准进行评估。

项目成果

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: 2022-11
• 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.

Exploring the Structural Space of Chemiluminescent 1,2-Dioxetanes

探索化学发光 1,2-二氧杂环丁烷的结构空间

• DOI: 10.1021/acssensors.2c02371
• 发表时间: 2023-01
• 期刊: ACS Sensors
• 影响因子: 8.9
• 作者: Haris, Uroob;Lippert, Alexander R.
• 通讯作者: Lippert, Alexander R.