S-nitroso-N-acetylpenicillamine | 67809-83-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: S-nitroso-N-acetylpenicillamine
• 英文别名: S-nitrosopenicillamine；S-nitroso-DL-penicillamine；S-nitroso-d,l-penicillamine；2-amino-3-methyl-3-nitrososulfanylbutanoic acid
• CAS: 67809-83-0
• 化学式: C₅H₁₀N₂O₃S
• 分子量: 178.212
• InChiKey: QLPXHECKUSZTMH-UHFFFAOYSA-N

物化性质

• 沸点：
  304.2±52.0 °C(Predicted)
• 密度：
  1.43±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -2.8
• 重原子数：
  11
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  118
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  S-nitroso-N-acetylpenicillamine 以 水 为溶剂， 生成 (2R)-2-氨基-3-[(3R)-3-氨基-4-羟基-2-甲基-4-氧代丁烷-2-基]二硫基-3-甲基丁酸
  参考文献：
  名称：

  The mechanism of nitric oxide formation from S-nitrosothiols (thionitrites)

  摘要：

  S-亚硝基硫醇 (RSNO) 通过硫醇的电亲核亚硝化反应容易制备，并且是氮氧化物的便捷来源。在 pH 7.4 的水缓冲液中（在许多情况下），反应会迅速发生，从而生成相应的二硫化物 RSSR。如果溶液中没有严格排除氧气，则一氧化氮会定量转化为亚硝酸盐离子，而在缺氧的情况下，可以通过商业一氧化氮探针检测到一氧化氮。然而，反应仅在存在 Cu2+ 的情况下发生（除了光化学途径）。通常在蒸馏水-缓冲液成分中有足够的 Cu2+ 促使反应发生，但如果 Cu2+ 与 EDTA 形成络合物，则分解会被阻止。然而，使用特定的 Cu+ 螯合剂新铜碱（neocuproine）进行的实验表明，真正的有效试剂是 Cu+，它是通过硫醇阴离子还原 Cu2+ 形成的。动力学实验表明，反应性最强的亚硝基硫醇是那些能够与 Cu+ 形成二配位的分子，而且在所研究的结构中反应性存在广泛的变异。反应性在很大程度上依赖于 Cu2+ 和 RS– 的浓度。当铜的来源是与三肽二甘氨基-L-组氨酸 (GGH) 的 CuII 络合物或与人血清白蛋白 (HSA) 的 CuII 络合物时，反应也会发生，虽然速度较慢。这使得亚硝基硫醇在原则上能够利用天然存在的 CuII 产生体内的一氧化氮。RSNO 中 NO 基团与硫醇之间的快速交换同样发生，在 pH 7.4 的水缓冲液中进行。此反应已被确定为硫醇阴离子在亚硝基氮原子上的亲核取代反应。讨论了这些结果对于亚硝基硫醇在体内可能参与的影响。

  DOI：

  10.1039/cc9960001085
• 作为产物：
  描述：

  DL-青霉胺 在 sodium nitrite 作用下， 以 水 为溶剂， 生成 S-nitroso-N-acetylpenicillamine
  参考文献：
  名称：

  氮亲核试剂对S-亚硝基芥酸的反应性

  摘要：

  我们报告了许多氮亲核试剂与亚硝基硫醇S-亚硝基葡糖胺（SPEN）反应的动力学研究结果。亲核试剂的范围包括伯，仲和叔脂族胺，以及肼，羟胺，叠氮化物离子，氨，氨基脲，硫吗啉和S-甲基半胱氨酸。仲胺定量地形成N-亚硝胺。如所预期的，反应通过亲核试剂的游离碱形式发生，因此大多数反应仅在相对较高的pH下容易发生。实验是用[亲核试剂]   [RSNO]进行的，对于许多反应，一阶速率常数与。[亲核试剂]是线性的。但是，对于氨和伯胺，该图倾向于在高[亲核试剂]时趋于平稳，并提供了一种解释，涉及可逆地形成无活性的RSNO-胺络合物，有光谱证据表明，与主要反应平行。对于仲胺，有一个很好的布朗斯台德图，β值约为0.2。与伯胺和吗啉相比，S-甲基半胱氨酸和硫代吗啉具有更高的反应性，这与在硫原子上的初始进攻，随后的内部重排相一致。在所研究的亲核试剂的整个范围内，与Ritchie N +参数存在合理的相关性，与Pea

  DOI：

  10.1039/a905901f

文献信息

• The reaction of <i>S</i>-nitrosothiols with thiols at high thiol concentration
  作者：Andrew P. Dicks、E. Li、Andrew P. Munro、Helen R. Swift、D. Lyn H. Williams

  DOI：10.1139/cjc-76-6-789

  日期：——

  Reactions of S-nitrosothiols (RSNO) with their corresponding thiols (RSH) present in a large excess (>20-fold) proceed readily to give the disulfide. Ammonia is formed together with some nitrite anion, and these constitute >90% of the "nitrogen" products. This is in marked contrast with the reaction at low thiol concentration, where nitric oxide is the major initial "nitrogen" product, which is rapidly converted in the presence of oxygen in water to nitrite anion. Also in marked contrast to the "low thiol concentration" reaction, the reaction at high thiol concentration is not affected by added Cu2+, nor by the metal-ion scavenger EDTA. Kinetically all reactions were excellent first-order processes, and the reactions were also strictly first order in thiol concentration. A large range of nitrosothiols were studied and the generality of the reaction established. Some reactions of RSNO with other thiols (R'SH) were examined and the results readily interpreted in terms of a prior rapid equilibrium transnitrosation. The pH dependence for the reaction of S-nitrosocysteine with cysteine clearly showed that the reactive species is the cysteine thiolate anion. The results are discussed along with those of two other recent reports of these reactions, in terms of thiolate attack initially at the nitroso nitrogen atom, and subsequently at sulfur atoms, eliminating RSSR and yielding hydroxylamine, which is rapidly reduced by thiolate ion to ammonia. The results are also discussed in connection with the release of NO from nitrosothiols and with the important biological consequences, both for the in vivo reactions of NO and for the potential of nitrosothiols as NO-releasing drugs for medical use.
• Munro, Andrew P.; Williams, D. Lyn H., Journal of the Chemical Society. Perkin Transactions 2 (2001), 2000, # 9, p. 1794 - 1797
  作者：Munro, Andrew P.、Williams, D. Lyn H.

  DOI：——

  日期：——
• Holmes, Anthony J.; Williams, D. Lyn H., Journal of the Chemical Society. Perkin Transactions 2 (2001), 2000, # 8, p. 1639 - 1644
  作者：Holmes, Anthony J.、Williams, D. Lyn H.

  DOI：——

  日期：——
• Barnett, D.Jonathan; Rios, Ana; Williams, D. Lyn H., Journal of the Chemical Society. Perkin transactions II, 1995, # 7, p. 1279 - 1282
  作者：Barnett, D.Jonathan、Rios, Ana、Williams, D. Lyn H.

  DOI：——

  日期：——
• The mechanism of nitric oxide formation from S-nitrosothiols (thionitrites)
  作者：D. Lyn H. Williams

  DOI：10.1039/cc9960001085

  日期：——

  S-Nitrosothiols (RSNO) are easily made by electrophilic nitrosation of thiols and are a convenient source of nitric oxide. Reaction occurs readily (in many cases) in aqueous buffer at pH 7.4 to give in addition the corresponding disulfide RSSR. If oxygen is not rigorously excluded from the solution, then the nitric oxide is converted quantitatively to nitrite ion, whereas in the absence of oxygen nitric oxide can be detected using a commercial NO-probe. Reaction, however, only occurs (apart from the photochemical pathway) if Cu2+ is present. There is often enough Cu2+ in the distilled water–buffer components to bring about reaction, but decomposition is halted if Cu2+ is complexed with EDTA. Experiments with the specific Cu+ chelator neocuproine however show that the true effective reagent is Cu+, formed by reduction of Cu2+ with thiolate ion. Kinetic experiments show that the most reactive nitrosothiols are those which can coordinate bidentately with Cu+, and there is a wide range of reactivity amongst the structures studied. Reactivity is crucially dependent on the concentrations of Cu2+ and RS–.Reaction also occurs, although somewhat more slowly, if the source of copper is the CuII complex with the tripeptide diglycyl-L-histidine (GGH) or as the CuII complex with human serum albumin (HSA). This allows the possibility that nitrosothiols could in principle generate nitric oxide in vivo using the naturally occurring sources of CuII.Rapid exchange of the NO-group in RSNO with thiols occurs, again in aqueous buffer at pH 7.4. This reaction has been established as a nucleophilic substitution reaction by the thiolate ion at the nitroso nitrogen atom.The implications of these results with regard to possible involvement of nitrosothiols in vivo are discussed.

  S-亚硝基硫醇 (RSNO) 通过硫醇的电亲核亚硝化反应容易制备，并且是氮氧化物的便捷来源。在 pH 7.4 的水缓冲液中（在许多情况下），反应会迅速发生，从而生成相应的二硫化物 RSSR。如果溶液中没有严格排除氧气，则一氧化氮会定量转化为亚硝酸盐离子，而在缺氧的情况下，可以通过商业一氧化氮探针检测到一氧化氮。然而，反应仅在存在 Cu2+ 的情况下发生（除了光化学途径）。通常在蒸馏水-缓冲液成分中有足够的 Cu2+ 促使反应发生，但如果 Cu2+ 与 EDTA 形成络合物，则分解会被阻止。然而，使用特定的 Cu+ 螯合剂新铜碱（neocuproine）进行的实验表明，真正的有效试剂是 Cu+，它是通过硫醇阴离子还原 Cu2+ 形成的。动力学实验表明，反应性最强的亚硝基硫醇是那些能够与 Cu+ 形成二配位的分子，而且在所研究的结构中反应性存在广泛的变异。反应性在很大程度上依赖于 Cu2+ 和 RS– 的浓度。当铜的来源是与三肽二甘氨基-L-组氨酸 (GGH) 的 CuII 络合物或与人血清白蛋白 (HSA) 的 CuII 络合物时，反应也会发生，虽然速度较慢。这使得亚硝基硫醇在原则上能够利用天然存在的 CuII 产生体内的一氧化氮。RSNO 中 NO 基团与硫醇之间的快速交换同样发生，在 pH 7.4 的水缓冲液中进行。此反应已被确定为硫醇阴离子在亚硝基氮原子上的亲核取代反应。讨论了这些结果对于亚硝基硫醇在体内可能参与的影响。