Metal Coordination Compounds as Reporters for Biological NO

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This Research award in the Inorganic, Bioinorganic and Organometallic Chemistry program supports work by Professor Stephen Lippard, Massachusetts Institute of Technology, to employ metal coordination complexes as reporting probes for biological nitric oxide (NO). Nitric oxide is an important molecule that controls many biological functions including smooth muscle dilation in the heart and other organs, signaling in the brain, and functioning of the immune system. 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. Included among the targets are units in proteins that contain iron or zinc bound to sulfur, and the reactions of these units with nitric oxide and its derivatives are being investigated to provide benchmarks for interpreting the chemistry that transduces the action of NO in living systems. Graduate and postdoctoral researchers on the project are mentors to undergraduate research opportunity participants at the Massachusetts Institute of Technology. These scientists are trained to communicate their work; many subsequently assume key positions in academic or industrial organizations and some are active in outreach programs at local schools in the Cambridge and Boston communities.Sensors for nitric oxide will facilitate the screening of chemical libraries for inhibitors of the enzyme that produces NO in Gram-positive bacteria such as anthrax and Staph. aureus, thus providing leads for novel antibiotics. The chemistry of nitric oxide with iron-sulfur clusters will help guide efforts to develop catalysts for environmental cleanup since nitrogen oxides are toxic byproducts of fuel combustion processes.