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Keywords = Piloty’s acid

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27 pages, 5677 KB  
Article
Developing Photoactive Coumarin-Caged N-Hydroxysulfonamides for Generation of Nitroxyl (HNO)
by Mohammad S. Rahman, Vinay Bharadwaj, Anau K. H. S. Lautaha, Paul Sampson, Nicola E. Brasch and Alexander J. Seed
Molecules 2024, 29(16), 3918; https://doi.org/10.3390/molecules29163918 - 19 Aug 2024
Cited by 1 | Viewed by 2791
Abstract
Photoactive N-hydroxysulfonamides photocaged with the (6-bromo-7-hydroxycoumarin-4-yl)methyl chromophore have been successfully synthesized, and the mechanisms of photodecomposition investigated for two of the compounds. Upon irradiation up to 97% of a diagnostic marker for (H)NO release, sulfinate was observed for the trifluoromethanesulfonamide system. In [...] Read more.
Photoactive N-hydroxysulfonamides photocaged with the (6-bromo-7-hydroxycoumarin-4-yl)methyl chromophore have been successfully synthesized, and the mechanisms of photodecomposition investigated for two of the compounds. Upon irradiation up to 97% of a diagnostic marker for (H)NO release, sulfinate was observed for the trifluoromethanesulfonamide system. In the absence of a species that reacts rapidly with (H)NO, (H)NO instead reacts with the carbocation intermediate to ultimately generate (E)-BHC-oxime and (Z)-BHC-oxime. Alternatively, the carbocation intermediate reacts with solvent water to give a diol. Deprotonation of the N(H) proton is required for HNO generation via concerted C-O/N-S bond cleavage, whereas the protonation state of the O(H) does not affect the observed photoproducts. If the N(H) is protonated, C-O bond cleavage to generate the parent N-hydroxysulfonamide will occur, and/or O-N bond cleavage to generate a sulfonamide. The undesired competing O-N bond cleavage pathway increases when the volume percentage of water in acetonitrile/water solvent mixtures is increased. Full article
(This article belongs to the Special Issue Synthesis and Application of Photoactive Compounds)
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10 pages, 1005 KB  
Communication
Para-Substituted O-Benzyl Sulfohydroxamic Acid Derivatives as Redox-Triggered Nitroxyl (HNO) Sources
by Yueming Long, Zijun Xia, Allison M. Rice and S. Bruce King
Molecules 2022, 27(16), 5305; https://doi.org/10.3390/molecules27165305 - 19 Aug 2022
Cited by 6 | Viewed by 2727
Abstract
Nitroxyl shows a unique biological profile compared to the gasotransmitters nitric oxide and hydrogen sulfide. Nitroxyl reacts with thiols as an electrophile, and this redox chemistry mediates much of its biological chemistry. This reactivity necessitates the use of donors to study nitroxyl’s chemistry [...] Read more.
Nitroxyl shows a unique biological profile compared to the gasotransmitters nitric oxide and hydrogen sulfide. Nitroxyl reacts with thiols as an electrophile, and this redox chemistry mediates much of its biological chemistry. This reactivity necessitates the use of donors to study nitroxyl’s chemistry and biology. The preparation and evaluation of a small library of new redox-triggered nitroxyl sources is described. The condensation of sulfonyl chlorides and properly substituted O-benzyl hydroxylamines produced O-benzyl-substituted sulfohydroxamic acid derivatives with a 27–79% yield and with good purity. These compounds were designed to produce nitroxyl through a 1, 6 elimination upon oxidation or reduction via a Piloty’s acid derivative. Gas chromatographic headspace analysis of nitrous oxide, the dimerization and dehydration product of nitroxyl, provides evidence for nitroxyl formation. The reduction of derivatives containing nitro and azide groups generated nitrous oxide with a 25–92% yield, providing evidence of nitroxyl formation. The oxidation of a boronate-containing derivative produced nitrous oxide with a 23% yield. These results support the proposed mechanism of nitroxyl formation upon reduction/oxidation via a 1, 6 elimination and Piloty’s acid. These compounds hold promise as tools for understanding nitroxyl’s role in redox biology. Full article
(This article belongs to the Section Bioorganic Chemistry)
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23 pages, 3233 KB  
Article
Synthesis of Nitric Oxide Donors Derived from Piloty’s Acid and Study of Their Effects on Dopamine Secretion from PC12 Cells
by Daniele Sanna, Gaia Rocchitta, Maria Serra, Marcello Abbondio, Pier Andrea Serra, Rossana Migheli, Lidia De Luca, Eugenio Garribba and Andrea Porcheddu
Pharmaceuticals 2017, 10(3), 74; https://doi.org/10.3390/ph10030074 - 5 Sep 2017
Cited by 9 | Viewed by 7999
Abstract
This study investigated the mechanisms and kinetics of nitric oxide (NO) generation by derivatives of Piloty’s acid (NO-donors) under physiological conditions. In order to qualitatively and quantitatively measure NO release, electron paramagnetic resonance (EPR) was carried out with NO spin trapping. In addition, [...] Read more.
This study investigated the mechanisms and kinetics of nitric oxide (NO) generation by derivatives of Piloty’s acid (NO-donors) under physiological conditions. In order to qualitatively and quantitatively measure NO release, electron paramagnetic resonance (EPR) was carried out with NO spin trapping. In addition, voltammetric techniques, including cyclic voltammetry and constant potential amperometry, were used to confirm NO release from Piloty’s acid and its derivatives. The resulting data showed that Piloty’s acid derivatives are able to release NO under physiological conditions. In particular, electron-withdrawing substituents favoured NO generation, while electron-donor groups reduced NO generation. In vitro microdialysis, performed on PC12 cell cultures, was used to evaluate the dynamical secretion of dopamine induced by the Piloty’s acid derivatives. Although all the studied molecules were able to induce DA secretion from PC12, only those with a slow release of NO have not determined an autoxidation of DA itself. These results confirm that the time-course of NO-donors decomposition and the amount of NO released play a key role in dopamine secretion and auto-oxidation. This information could drive the synthesis or the selection of compounds to use as potential drugs for the therapy of Parkinson’s disease (PD). Full article
(This article belongs to the Special Issue Choices of the Journal)
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