Fluorophore Coordinated Transition Metal Complexes for Sensing Neuronal Nitric Oxide

用于传感神经元一氧化氮的荧光团配位过渡金属配合物

• 批准号: 0234951
• 负责人: Stephen Lippard
• 金额: --
• 依托单位: Massachusetts Institute of Technology
• 依托单位国家: 美国
• 项目类别: Continuing grant
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-01-01 至 2006-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0234951&HistoricalAwards=false
• 关键词: Fluorophore; Coordinated; Transition; Metal; Complexes

This award by the Inorganic, Bioinorganic and Organometallic Chemistry program supports research by Professor Stephen J. Lippard at MIT to use carboxylate-bridged dimetallic complexes, mononuclear analogs and other transition metal complexes to develop water-soluble sensors for nitric oxide in neurochemical applications. Nitric oxide (NO) is an important neurotransmitter, the generation and disposition of which are difficult to track in neuronal cells. Dinuclear tetracarboxalato bridged complexes containing Fe, Co and other metals ions, and N-donor ligands bearing fluorescent dansyl or fluorescein-type units, will be used as NO sensors. The ligands, the bright fluorescence of which is quenched when bound to the transition metal complexes, afford a sensitive method for NO detection when released upon NO coordination to the metal. Water-soluble versions will be prepared for applications in neuroscience. Mono- and dinuclear iron(II) complexes bearing N-methyliminodiacetate (mida) units tethered to fluorophores will also be synthesized for monitoring reversible NO binding. These complexes will be used to study early steps in dioxygen activation, which NO can imitate. Additional transition metal analogs will be studied in order to optimize the quenching of the bound fluorophore and to achieve reversibility. Carboxylates bearing coordinating fluorophores on tethers will help accomplish the latter goal.Attaining the scientific goals will facilitate the measurement of a key signaling molecule in the brain. Graduate and postdoctoral researchers are mentors to undergraduate research opportunity participants (UROPs) at MIT. The infrastructure of research and education is enhanced by collaborations with scientists at other institutions and disciplines. A diverse set of co-workers will participate and will be trained to communicate their work and assume key positions in academic or industrial organizations, as indicated by this research group's web site http://methane.lms.mit.edu:8001/group/. Sensors for nitric oxide, a key molecule in the brain involved in neuronal signaling, development and disease, will be designed and synthesized. Workers will be trained broadly across the fields of inorganic chemistry and neuroscience

无机，生物无机和有机化学计划的这一奖项支持麻省理工学院的Stephen J. Lippard教授使用羧酸根桥接的双金属络合物，单核类似物和其他过渡金属络合物开发神经化学应用中一氧化氮的水溶性传感器。 一氧化氮（Nitric oxide，NO）是一种重要的神经递质，其在神经细胞中的产生和分布难以追踪。 含有Fe、Co和其他金属离子的双核四羧酸根桥连配合物，以及带有荧光丹酰或荧光素型单元的N-供体配体，将用作NO传感器。 配体，其明亮的荧光被淬灭时，绑定到过渡金属配合物，提供了一个灵敏的方法NO检测时，NO配位释放到金属。 水溶性版本将准备在神经科学中的应用。 单核和双核铁（II）配合物轴承N-甲基亚氨基二乙酸（米达）单位拴在荧光团也将被合成用于监测可逆的NO结合。这些复合物将被用来研究分子氧活化的早期步骤，NO可以模仿。另外的过渡金属类似物将进行研究，以优化结合的荧光团的淬灭，并实现可逆性。羧酸酯在拴系物上带有协调荧光团将有助于实现后一个目标。实现科学目标将有助于测量大脑中的一个关键信号分子。 研究生和博士后研究人员是麻省理工学院本科生研究机会参与者（UROP）的导师。 通过与其他机构和学科的科学家合作，加强了研究和教育的基础设施。 如该研究小组的网站http://methane.lms.mit.edu:8001/group/所示，各种各样的同事将参加并接受培训，以交流他们的工作，并在学术或工业组织中担任关键职位。 将设计和合成一氧化氮传感器，一氧化氮是大脑中参与神经元信号传导、发育和疾病的关键分子。 工人将接受广泛的无机化学和神经科学领域的培训