Download or read book Phosphine Based Fluorescent Probes for Nitroxyl Detection and Their Reactivity Toward S-nitrosothiols written by Zhengrui Miao and published by . This book was released on 2016 with total page 152 pages. Available in PDF, EPUB and Kindle. Book excerpt: Nitrogen oxides are a unique class of molecules with profound physiology. Nitric oxide (NO), the most well-studied nitrogen oxide, plays a key role in modulating numerous physiological processes such as blood pressure control and the immune response. Nitroxyl (HNO), the one-electron reduced/protonated relative of NO, possesses a distinct physiological profile from NO. HNO inhibits the activity of various thiol-containing enzymes and regulates cardiovascular signaling, making it an intriguing candidate for many physiological disorders such as alcoholism and congestive heart failure (CHF). Despite its physiological significance, the lack of reliable detection methods still hampers our understanding of HNO. To help overcome this problem, we developed a novel fluorescein-derived fluorescent probe for HNO based on the reductive Staudinger ligation. This probe allows detection of HNO from various sources without the interference of other biological redox species. This probe also successfully detects HNO by fluorescence in HeLa cells following the designed mechanism. We noticed similar reactivity between S-nitrosothiols (RSNO) with this type of probe. To investigate this potential cross-reactivity, we compared the phosphine-based detection strategies for HNO and RSNO. Phosphorus NMR studies show that azaylides derived from HNO or organic RSNO efficiently participate in the reductive ligation required for fluorescence generation while S-azaylides derived from biological RSNO containing free amine and carboxylic acid groups primarily yield phosphine oxides, allowing the use of phosphine probes for selective HNO detection. Flow cytometry experiments in HeLa cells reinforce the reactivity difference and offer a potential fast screening approach for endogenous HNO sources. We also proposed the existence of S-nitrosobacillithiol (BSNO), the corresponding RSNO for bacillithiol (BSH). We attempted the synthesis and characterization of BSNO. Though this work is still on-going, we believe the success of this project will boost the understanding of the roles that BSH and BSNO play in low-guanine-cytosine (G+C) content Gram-positive bacteria.