The role of nitric oxide (NO) in biology has received much attention over the past several years. Indeed, NO has been shown to play a fundamental role in several key biochemical processes including blood pressure control and neurotransmission. However, NO is also implicated in a variety of neurodegenerative disorders such as Alzheimer's and Parkinson's disease. Unfortunately: unraveling the various biological functions of NO is often deterred by a lack of methodology to visulaize it directly and provode spatial and temporal information about its distribution. In the present study we intend to synthesize fluorescent NO sensor molecules for visual marking of NO with the goal of discerning its function(s) in the various physiological processes. In this regard we will take advantage of the fluorescence quenching properties of Cu(ll) centers when coordinated to fluorescent ligand moieties representing the OFF state of the sensor. In presence of NO, the Cu(ll) center will be reduced to Cu(l) resulting in a diamagnetic species turning the fluorescence ON and signalling the presence of this neurotransmitter. The current approach provides an improved methodology to sense NO and will find wide use for imaging NO in biological samples.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32GM075684-01
Application #
6999910
Study Section
Special Emphasis Panel (ZRG1-F04A (20))
Program Officer
Fabian, Miles
Project Start
2005-09-20
Project End
2008-09-19
Budget Start
2005-09-20
Budget End
2006-09-19
Support Year
1
Fiscal Year
2005
Total Cost
$42,068
Indirect Cost
Name
Massachusetts Institute of Technology
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
001425594
City
Cambridge
State
MA
Country
United States
Zip Code
02139
Harrop, Todd C; Tonzetich, Zachary J; Reisner, Erwin et al. (2008) Reactions of synthetic [2Fe-2S] and [4Fe-4S] clusters with nitric oxide and nitrosothiols. J Am Chem Soc 130:15602-10
Harrop, Todd C; Song, Datong; Lippard, Stephen J (2007) Reactivity pathways for nitric oxide and nitrosonium with iron complexes in biologically relevant sulfur coordination spheres. J Inorg Biochem 101:1730-8
Conradie, Jeanet; Quarless Jr, Duncan A; Hsu, Hua-Fen et al. (2007) Electronic structure and FeNO conformation of nonheme iron-thiolate-NO complexes: an experimental and DFT study. J Am Chem Soc 129:10446-56
Harrop, Todd C; Song, Datong; Lippard, Stephen J (2006) Interaction of nitric oxide with tetrathiolato iron(II) complexes: relevance to the reaction pathways of iron nitrosyls in sulfur-rich biological coordination environments. J Am Chem Soc 128:3528-9