Metal Coordination Compounds as Reporters for Biological NO

一氧化氮（NO）是一种重要的分子，其控制许多生物过程，包括心脏和其他器官中的平滑肌扩张、神经传递和免疫系统的功能。通过这个奖项，由化学系的化学结构，动力学和机制B计划资助，来自马萨诸塞州理工学院的Stephen J. Lippard教授将研究一氧化氮与过渡金属络合物的化学反应，这些络合物可以被纳入新的基于肽的平台，用于检测生物学中的信号传导剂。该项目通过基于过渡金属化学的明亮发光分子的制备和应用来研究这些作用，以跟踪一氧化氮的产生和转移到其生物靶点。这些目标中的一些包括过渡金属中心，并且它们响应NO的化学反应是另一个研究主题。通过将传感器定向到特定的细胞区域，如细胞膜或细胞器，如细胞外基质，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。反应物种来自NO，特别是HNO（硝酰基）和HSNO（亚硝基硫醇），也将进行研究。通过化学反应，探针将对NO、HNO或HSNO具有选择性，动力学调节为快速开启，比率计量以允许定量，可逆，并且能够在低能量下发射以最小化不需要的背景。在传感器的设计和实施过程中发现的化学动力学和机制可能与生命系统相似，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。肽提供了一个很好的平台，用于整合单元以将传感器定位到亚细胞区域，这对于研究活细胞和组织切片中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，都可以预见到它的应用。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。鼓励这些科学家口头和书面交流他们的工作。许多人随后在学术或工业组织中担任重要职务，有些人积极参与当地社区学校的外联方案。

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.