Para-Substituted <i>O</i>-Benzyl Sulfohydroxamic Acid Derivatives as Redox-Triggered Nitroxyl (HNO) Sources
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 chemis...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-08-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/16/5305 |
| _version_ | 1827598919464386560 |
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| author | Yueming Long Zijun Xia Allison M. Rice S. Bruce King |
| author_facet | Yueming Long Zijun Xia Allison M. Rice S. Bruce King |
| author_sort | Yueming Long |
| collection | DOAJ |
| description | 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 <i>O</i>-benzyl hydroxylamines produced <i>O</i>-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. |
| first_indexed | 2024-03-09T04:01:46Z |
| format | Article |
| id | doaj.art-b2db7ae3597d403eb313fa0fe8e3064f |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T04:01:46Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-b2db7ae3597d403eb313fa0fe8e3064f2023-12-03T14:12:09ZengMDPI AGMolecules1420-30492022-08-012716530510.3390/molecules27165305Para-Substituted <i>O</i>-Benzyl Sulfohydroxamic Acid Derivatives as Redox-Triggered Nitroxyl (HNO) SourcesYueming Long0Zijun Xia1Allison M. Rice2S. Bruce King3Department of Chemistry, Wake Forest University, Winston-Salem, NC 27101, USADepartment of Chemistry, Wake Forest University, Winston-Salem, NC 27101, USADepartment of Chemistry, Wake Forest University, Winston-Salem, NC 27101, USADepartment of Chemistry, Wake Forest University, Winston-Salem, NC 27101, USANitroxyl 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 <i>O</i>-benzyl hydroxylamines produced <i>O</i>-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.https://www.mdpi.com/1420-3049/27/16/5305nitroxyl (HNO)Piloty’s acidredox triggered 1, 6 eliminationgasotransmittersredox signalingaromatic nitro/azide reduction |
| spellingShingle | Yueming Long Zijun Xia Allison M. Rice S. Bruce King Para-Substituted <i>O</i>-Benzyl Sulfohydroxamic Acid Derivatives as Redox-Triggered Nitroxyl (HNO) Sources Molecules nitroxyl (HNO) Piloty’s acid redox triggered 1, 6 elimination gasotransmitters redox signaling aromatic nitro/azide reduction |
| title | Para-Substituted <i>O</i>-Benzyl Sulfohydroxamic Acid Derivatives as Redox-Triggered Nitroxyl (HNO) Sources |
| title_full | Para-Substituted <i>O</i>-Benzyl Sulfohydroxamic Acid Derivatives as Redox-Triggered Nitroxyl (HNO) Sources |
| title_fullStr | Para-Substituted <i>O</i>-Benzyl Sulfohydroxamic Acid Derivatives as Redox-Triggered Nitroxyl (HNO) Sources |
| title_full_unstemmed | Para-Substituted <i>O</i>-Benzyl Sulfohydroxamic Acid Derivatives as Redox-Triggered Nitroxyl (HNO) Sources |
| title_short | Para-Substituted <i>O</i>-Benzyl Sulfohydroxamic Acid Derivatives as Redox-Triggered Nitroxyl (HNO) Sources |
| title_sort | para substituted i o i benzyl sulfohydroxamic acid derivatives as redox triggered nitroxyl hno sources |
| topic | nitroxyl (HNO) Piloty’s acid redox triggered 1, 6 elimination gasotransmitters redox signaling aromatic nitro/azide reduction |
| url | https://www.mdpi.com/1420-3049/27/16/5305 |
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