Mechanistic Insights into Rapid Generation of Nitroxyl from a Photocaged N-Hydroxysulfonamide Incorporating the (6-Hydroxynaphthalen-2-yl)methyl Chromophore.

The Journal of Organic Chemistry
Ruth B CinkNicola E Brasch

Abstract

HNO is a highly reactive molecule that shows promise in treating heart failure. Molecules that rapidly release HNO with precise spatial and temporal control are needed to investigate the biology of this signaling molecule. (Hydroxynaphthalen-2-yl)methyl-photocaged N-hydroxysulfonamides are a new class of photoactive HNO generators. Recently, it was shown that a (6-hydroxynaphthalen-2-yl)methyl (6,2-HNM)-photocaged derivative of N-hydroxysulfonamide incorporating the trifluoromethanesulfonamidoxy group (1) quantitatively generates HNO. Mechanistic studies have now been carried out on this system and reveal that the ground state protonation state plays a key role in whether concerted heterolytic C-O/N-S bond cleavage to release HNO occurs versus undesired O-N bond cleavage. N-Deprotonation of 1 can be achieved by adding an aqueous buffer or a carboxylate salt to an aprotic solvent. Evidence is presented for C-O/N-S bond heterolysis occurring directly from the singlet excited state of the N-deprotonated parent molecule on the picosecond time scale, using femtosecond time-resolved transient absorption spectroscopy, to give a carbocation and 1NO-. This is consistent with the observation of significant fluorescence quenching when HNO...Continue Reading

References

Jul 20, 1966·Journal of the American Chemical Society·H I Joschek, L I Grossweiner
May 29, 2002·Proceedings of the National Academy of Sciences of the United States of America·Vladimir Shafirovich, Sergei V Lymar
Feb 6, 2003·Journal of the American Chemical Society·Andrew D CohenJohn P Toscano
Jul 17, 2003·Proceedings of the National Academy of Sciences of the United States of America·Katrina M MirandaDavid A Wink
Oct 28, 2004·Journal of the American Chemical Society·Sara N RichterMauro Freccero
Aug 17, 2005·Current Topics in Medicinal Chemistry·Katrina M MirandaJohn P Toscano
Jul 15, 2006·The Journal of Physical Chemistry. a·Noam Agmon
Oct 29, 2008·Chemical Communications : Chem Comm·Yusuke AdachiNaoki Miyata
Jun 23, 2009·Free Radical Biology & Medicine·Jon M FukutoTyler A Chavez
Apr 16, 2010·Chemical Communications : Chem Comm·Kazuya MatsuoNaoki Miyata
Sep 25, 2010·Journal of the American Chemical Society·Daniela VergaMauro Freccero
Apr 27, 2012·The Journal of Organic Chemistry·Jelena VeljkovićNikola Basarić
Sep 24, 2013·Photochemical & Photobiological Sciences : Official Journal of the European Photochemistry Association and the European Society for Photobiology·Dani SkalameraNikola Basarić
Apr 25, 2014·The Journal of Organic Chemistry·Đani ŠkalameraNikola Basarić
Apr 2, 2016·The Journal of Organic Chemistry·Filippo DoriaMauro Freccero
Sep 17, 2016·Angewandte Chemie·Yang ZhouPaul Sampson
Feb 16, 2017·Physical Chemistry Chemical Physics : PCCP·L J G W van WilderenJ Bredenbeck
Apr 28, 2017·Chemical Communications : Chem Comm·G CarroneF Doctorovich
Sep 20, 2017·Journal of the American Chemical Society·Sebastian A SuarezFabio Doctorovich
Jun 3, 2018·British Journal of Pharmacology·Jon M Fukuto
Aug 29, 2018·Chemical Communications : Chem Comm·Mitsuyasu KawaguchiHidehiko Nakagawa
Mar 8, 2019·The Journal of General Physiology·Gizem KeceliJohn P Toscano
May 10, 2019·Heart Failure Reviews·Yanqing GuoJian An
Jun 7, 2019·European Journal of Heart Failure·G Michael FelkerJohn J V McMurray

❮ Previous
Next ❯

Citations


❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.