Department of Chemistry, Wake Forest University, Winston-Salem, NC 27101, USA.
Molecules. 2022 Aug 19;27(16):5305. doi: 10.3390/molecules27165305.
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 -benzyl hydroxylamines produced -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.
与气体递质一氧化氮和硫化氢相比，亚硝酰显示出独特的生物学特性。亚硝酰与硫醇反应作为亲电试剂，这种氧化还原化学介导了其大部分生物学化学。这种反应性需要使用供体来研究亚硝酰的化学和生物学。描述了一种新的氧化还原触发亚硝酰源的小文库的制备和评价。磺酰氯和适当取代的 - 苄基羟胺的缩合产生了 - 苄基取代的磺羟肟酸衍生物，产率为 27-79％，纯度良好。这些化合物旨在通过氧化或还原通过 Piloty 酸衍生物发生 1,6 消除来产生亚硝酰。亚硝酰二聚体和脱水产物一氧化二氮的气相色谱顶空分析为亚硝酰形成提供了证据。含有硝基和叠氮基团的衍生物的还原生成一氧化二氮，产率为 25-92％，为亚硝酰形成提供了证据。含硼酸酯的衍生物的氧化生成一氧化二氮，产率为 23％。这些结果支持通过 1,6 消除和 Piloty 酸的还原/氧化形成亚硝酰的提议机制。这些化合物有望成为理解亚硝酰在氧化还原生物学中作用的工具。
