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Published on: August 20, 2012
A Chemiluminescent Probe for HNO Quantification and Real-Time Monitoring in Living Cells
Weiwei An1, Lucas S Ryan1, Audrey G Reeves1
1Department of Chemistry, Center for Drug Discovery, Design, and Delivery (CD4), and, Center for Global Health Impact (CGHI), Southern Methodist University, Dallas, TX, 75205-0314, USA.
Abstract:
Azanone (HNO) is a reactive nitrogen species with pronounced biological activity and high therapeutic potential for cardiovascular dysfunction. A critical barrier to understanding the biology of HNO and furthering clinical development is the quantification and real-time monitoring of its delivery in living systems. Herein, we describe the design and synthesis of the first chemiluminescent probe for HNO, HNOCL-1, which can detect HNO generated from concentrations of Angeli's salt as low as 138 nm with high selectivity based on the reaction with a phosphine group to form a self-cleavable azaylide intermediate. We have capitalized on this high sensitivity to develop a generalizable kinetics-based approach, which provides real-time quantitative measurements of HNO concentration at the picomolar level. HNOCL-1 can monitor dynamics of HNO delivery in living cells and tissues, demonstrating the versatility of this method for tracking HNO in living systems.
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