Fluorophore Coordinated Transition Metal Complexes for Sensing Neuronal Nitric Oxide

该奖项由无机、生物无机和有机金属化学项目颁发，支持麻省理工学院Stephen J. Lippard教授使用羧酸桥接双金属配合物、单核类似物和其他过渡金属配合物开发用于神经化学应用的一氧化氮水溶性传感器的研究。一氧化氮（NO）是一种重要的神经递质，其在神经元细胞中的生成和分布难以追踪。含有铁、钴等金属离子的双核四羧酸桥接配合物和带有荧光丹酰或荧光素型单元的n给体配体将被用作NO传感器。当配体与过渡金属配合物结合时，其明亮的荧光被猝灭，当NO与金属配位释放时，提供了一种灵敏的检测NO的方法。水溶性版本将准备应用于神经科学。还将合成带有n -甲基二乙酸（mida）单元的单核和双核铁（II）配合物，用于监测可逆的NO结合。这些配合物将用于研究一氧化氮可以模仿的二氧活化的早期步骤。额外的过渡金属类似物将被研究，以优化结合荧光团的淬火和实现可逆性。在系链上携带配位荧光团的羧酸盐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。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，一组不同的同事将参加并接受培训，以交流他们的工作，并担任学术或工业组织的关键职位。一氧化氮是大脑中参与神经元信号、发育和疾病的关键分子，其传感器将被设计和合成。工作人员将接受无机化学和神经科学领域的广泛培训

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