Metal Coordination Compounds as Reporters for Biological NO

一氧化氮(NO)是一种重要的分子，它控制着许多生物过程，包括心脏和其他器官的平滑肌扩张、神经传递和免疫系统的功能。通过这项由化学系化学结构、动力学和机制B计划资助的奖项，麻省理工学院的Stephen J.Lippard教授将研究一氧化氮与过渡金属络合物的化学，这些络合物可以被整合到基于多肽的新型平台中，作为生物学中的信号媒介进行检测。该项目通过制备和应用基于过渡金属化学的明亮发光分子来研究这些作用，以跟踪一氧化氮的产生和转移到其生物目标。其中几个目标包括过渡金属中心，它们对NO的反应化学是另一个研究对象。通过将传感器定向到特定的细胞位置，如细胞膜或线粒体等细胞器，可以通过荧光显微镜研究获得关于NO作为信号转导分子的时空信息。来自NO的活性物种，特别是HNO(氮氧基)和HSNO(亚硝硫醇)，也将被调查。通过化学方法，探测器将对NO、HNO或HSNO具有选择性，动态调节以快速开启，比率测量以允许定量、可逆，并能够在低能量下发射以最大限度地减少不需要的背景。在传感器的设计和实现过程中发现的化学动力学和机理可能在生命系统中具有类似的作用，从而丰富了我们对过渡金属中心如何响应一氧化氮及其衍生物的知识。多肽为将传感器定位到亚细胞区域提供了一个很好的平台，这对于研究活细胞和组织切片的功能是一个很大的优势。从抗生素的设计到确定一氧化氮在感官知觉中的作用，都可以预见到各种应用。这些项目将继续培训年轻的化学科学家。该项目的研究生和博士后研究人员也是麻省理工学院本科生研究机会参与者(UROP)的导师。鼓励这些科学家以口头和书面形式交流他们的工作。许多人随后在学术或行业组织中担任关键职位，一些人活跃在当地社区学校的外联计划中。

Nitric oxide (NO) is an important molecule that controls many biological processes including smooth muscle dilation in the heart and other organs, neurotransmission, and functioning of the immune system. Through this award, funded by the Chemical Structure, Dynamics, and Mechanisms B Program of the Division of Chemistry, Professor Stephen J. Lippard from the Massachusetts Institute of Technology will investigate the chemistry of nitric oxide with transition metal complexes that can be incorporated into novel, peptide-based, platforms for its detection as a signaling agent in biology. This project investigates these roles through the preparation and application of bright, light-emitting molecules based on transition metal chemistry to track the generation and translocation of nitric oxide to its biological targets. Several of these targets include transition metals centers, and the chemistry by which they respond to NO is another subject of investigation. By directing the sensors to specific cellular locales, such as the cell membrane or organelles like the mitochondrion, spatiotemporal information about NO as a signal transduction molecule can be obtained by fluorescence microscopic studies. Reactive species derived from NO, specifically HNO (nitroxyl) and HSNO (nitrosothiol), will also be investigated. Through chemistry, the probes will be made selective for NO, HNO, or HSNO, kinetically tuned for rapid turn-on, ratiometric to allow for quantitation, reversible, and able to emit at low energies to minimize unwanted background. The chemical dynamics and mechanisms discovered during the design and implementation of the sensors may have parallels in living systems and thereby enrich our knowledge of how transition metal centers respond to nitric oxide and its derivatives. Peptides provide an excellent platform for incorporating units to localize the sensors to subcellular locales, a great advantage for studying functions in live cells and tissue slices. Applications ranging from the design of antibiotics to the determination of the roles of nitric oxide in sensory perception can be envisioned. These projects will continue the training of young scientists in chemistry. Graduate and postdoctoral researchers on the project are also mentors to undergraduate research opportunity participants (UROPs) at MIT. These scientists are encouraged to communicate their work both orally and in writing. Many subsequently assume key positions in academic or industrial organizations and some are active in outreach programs at schools in the local communities.