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Small molecule probes for peroxynitrite detection
Aleksandra Grzelakowska ; Balaraman Kalyanaraman ; Jacek Zielonka RBC,2024,100034. DOI: 10.1016/j.rbc.2024.100034
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Abstract: Peroxynitrite (ONOO?/ONOOH) is a short-lived but highly reactive species that is formed in the diffusion-controlled reaction between nitric oxide and the superoxide radical anion. It can oxidize certain biomolecules and has been considered as a key cellular oxidant formed under various pathophysiological conditions. It is crucial to selectively detect and quantify ONOO– to determine its role in biological processes. In this review, we discuss various approaches used to detect ONOO? in cell-free and cellular systems with the major emphasis on small-molecule chemical probes. We review the chemical principles and mechanisms responsible for the formation of the detectable products, and plausible limitations of the probes. We recommend the use of boronate-based chemical probes for ONOO?, as they react directly and rapidly with ONOO–, they produce minor but ONOO??specific products, and the reaction kinetics and mechanism have been rigorously characterized. Specific experimental approaches and protocols for the detection of ONOO– in cell-free, cellular, and in vivo systems using boronate-based molecular probes are provided (as shown in BOX 1, BOX 2, BOX 3, BOX 4, BOX 5, BOX 6).
Keywords: peroxynitrite ; molecular probes ; fluorescence ; bioluminescence ; chromatography ; biomarkers
Purchased from AmBeed: 1357078-03-5 ; 1449-46-3 ; 93-35-6 ; 23308-83-0 ; 91-64-5 ; 70340-04-4
CAS No. : | 93-35-6 | MDL No. : | MFCD00006878 |
Formula : | C9H6O3 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | ORHBXUUXSCNDEV-UHFFFAOYSA-N |
M.W : | 162.14 | Pubchem ID : | 5281426 |
Synonyms : |
7-Hydroxycoumarin;Hydrangin;7-Hydroxycoumarin, 7 Hydroxycoumarin, 7Hydroxycoumarin, Hydrangin, Skimmetin, Umbelliferone;beta-umbelliferone;skimmetine;hydrangine;NSC 19790
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Chemical Name : | 7-Hydroxy-2H-chromen-2-one |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
52% | With di-isopropyl azodicarboxylate; triethylamine; triphenylphosphine; In tetrahydrofuran; at 0 - 20℃; | Step A: Diisopropyl azodicarboxylate (5.5 mL, 28 mmol) was added dropwise to a mixture of 7-hydroxycoumarin (4.6 g, 28 mmol), (R)-tert-butyl 3-hydroxypyrrolidine-l- carboxylate (6.0 g, 31 mmol), triphenylphosphine (7.4 g, 28 mmol) and triethylamine (3.9 mL, 28 mmol) in THF (28 mL) at 0 C. The mixture was stirred at room temperature overnight. The solids were removed by filtration and washed with cold THF. The solid was dissolved in EtOAc. The solution was washed with aqueous HC1 (0.5 N), dried over NaS04, then filtered and concentrated to give (S)-tert-butyl 3-(2-oxo-2H-chromen-7-yloxy)pyrrolidine-l-carboxylate (4.85 g, 52%) as a pale yellow solid. MS m/z 232.2 [M-Boc+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
52% | With di-isopropyl azodicarboxylate; triethylamine; triphenylphosphine; In tetrahydrofuran; at 0 - 20℃; for 16h; | Step A: Diisopropyl azodicarboxylate (5.5 mL, 28 mmol) was added dropwise to a mixture of 7-hydroxycoumarin (4.6 g, 28 mmol), <strong>[109431-87-0](R)-tert-butyl 3-hydroxypyrrolidine-1-carboxylate</strong> (6.0 g, 31 mmol), triphenylphosphine (7.4 g, 28 mmol) and triethylamine (3.9 mL, 28 mmol) in THF (28 mL) at 0 C. The mixture was stirred at room temperature overnight. The solids were removed by filtration and washed with cold THF. The solid was dissolved in EtOAc. The solution was washed with aqueous HCl (0.5 N), dried over NaSO4, then filtered and concentrated to give (S)-tert-butyl 3-(2-oxo-2H-chromen-7-yloxy)pyrrolidine-1-carboxylate (4.85 g, 52%) as a pale yellow solid. MS m/z 232.2 [M-Boc+H]+. |