Fluorophore Coordinated Transition Metal Complexes for Sensing Neuronal Nitric Oxide

Massachusetts Institute Of Technology, Cambridge MA

Investigators

Abstract

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