Fluorophore Coordinated Transition Metal Complexes for Sensing Neuronal Nitric Oxide

这项由无机化学、生物无机化学和金属有机化学项目颁发的奖项支持麻省理工学院的Stephen J.Lippard教授的研究，即使用羧酸桥联的双金属络合物、单核类似物和其他过渡金属络合物来开发神经化学应用中的一氧化氮水溶传感器。一氧化氮(NO)是一种重要的神经递质，其在神经细胞中的产生和分布很难追踪。含有铁、钴等金属离子的双核四酸桥联络合物，以及含有荧光丹磺酰基或荧光素型单元的N-给体配体，将被用作NO传感器。当配体与过渡金属络合物结合时，其明亮的荧光被猝灭，当与金属没有配位时释放时，为NO的检测提供了一种灵敏的方法。将准备用于神经科学的水溶性版本。还将合成含有N-甲基亚氨二乙酸酯(MIDA)单元与荧光团连接的单核和双核铁(II)配合物，以监测可逆的NO结合。这些络合物将被用来研究氧气活化的早期步骤，NO可以模仿。将研究更多的过渡金属类似物，以优化结合的荧光团的猝灭并实现可逆性。在系绳上带有协调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。一组不同的同事将参与并接受培训，以交流他们的工作，并在学术或行业组织中担任关键职位，如该研究小组的网站http://methane.lms.mit.edu:8001/group/.所示一氧化氮传感器是大脑中参与神经元信号传递、发育和疾病的关键分子，将被设计和合成。工人们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