Identification of Cu+ as the effective reagent in nitric oxide formation from S-nitrosothiols (RSNO)
Identification of Cu+ as the effective reagent in nitric oxide formation from S-nitrosothiols (RSNO)
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DOI：
10.1039/p29960000481
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发表时间：
1996-04-01
期刊：
影响因子：
--
通讯作者：
Cox, BG
中科院分区：
文献类型：
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作者：
Dicks, AP;Swift, HR;Cox, BG
S-亚硝基硫醇（RSNO）在pH 7.4的水溶液中的分解是由铜离子引起的，铜离子作为杂质存在或专门添加。主要产物是一氧化氮和二硫化物。在特异性Cu+螯合剂新亚铜灵的存在下，随着[新亚铜灵]的增加，反应逐渐被抑制，反应最终完全停止。从反应溶液中可以获得Cu+加合物的特征UV-VIS光谱。这清楚地表明Cu+而不是Cu 2+是有效的催化剂。两个限制动力学条件可以确定为一系列的S-亚硝基硫醇在特定的铜离子浓度（a）的一级依赖性和（B）的零级依赖于[RSNO]。通常这两种情况也有一个短的诱导期。该诱导期可通过添加相应的硫醇RSH来去除。提出了一种机制，其中Cu+是通过还原Cu 2+的硫醇盐阴离子通过中间体，可能RSCu（+）。从RSNO中损失一氧化氮是由Cu+引起的，可能是通过另一个中间体，其中Cu+与NO基团的氮原子和另一个富电子原子（如氨基中的氮或羧酸根中的氧）结合，涉及六元环。与NO一样，这产生RS（-）和Cu 2+，它们是再生Cu+循环的一部分。硫醇根离子被氧化为RS（.）其二聚化得到二硫化物。取决于RSNO的结构（以及因此的反应性），Cu+形成或其与RSNO的反应可以是限速的。反应方案的计算机建模允许生成与实验生成的形式相同的吸收时间图，即一阶或零阶，有或没有诱导期。我们建议，硫醇离子带来的铜+还原是必要的，要么是作为硫醇杂质或产生少量的亚硝基硫醇，这导致在诱导期的部分水解。添加少量的硫醇去除诱导期，并导致催化，但大量带来的速率降低，它建议，络合的Cu 2+。对于两个非常不反应的底物，S-亚硝基谷胱甘肽和S-亚硝基-N-乙酰半胱氨酸非常大的诱导期观察到，通常为3小时。这一结果，我们建议，从竞争再氧化的Cu+到Cu 2+的溶解氧。在厌氧条件下进行的实验证实了这一点，因为没有诱导期。添加过氧化氢进一步延长诱导期。结果进行了讨论，S-亚硝基硫醇的生物学特性，这是有关一氧化氮的释放。
Decomposition of S-nitrosothiols (RSNO) in aqueous solution at pH 7.4 is brought about by copper ions, either present as an impurity or specifically added. The primary products are nitric oxide and the disulfide. In the presence of the specific Cu+ chelator, neocuproine, reaction is progressively inhibited as the [neocuproine] is increased, the reaction eventually stopping completely. The characteristic UV-VIS spectrum of the Cu+ adduct can be obtained from the reaction solutions. This shows clearly that Cu+ and not Cu2+ is the effective catalyst. Two limiting kinetic conditions can be identified for a range of S-nitrosothiols at specific copper ion concentrations (a) a first-order dependence and (b) a zero-order dependence upon [RSNO]. Normally both situations also have a short induction period. This induction period can be removed by the addition of the corresponding thiol RSH. A mechanism is proposed in which Cu+ is formed by reduction of Cu2+ by thiolate anion via an intermediate, possibly RSCu(+). Loss of nitric oxide from RSNO is then brought about by Cu+, probably via another intermediate in which Cu+ is bound to the nitrogen atom of the NO group and another electron-rich atom (such as nitrogen from an amino group, or oxygen from a carboxylate group) involving a six-membered ring. As well as NO this produces both RS(-) and Cu2+ which then are part of the cycle regenerating Cu+. Thiolate ion is oxidised to RS(.) which dimerizes to give the disulfide. Depending on the structure (and hence reactivity) of RSNO either Cu+ formation or its reaction with RSNO can be rate-limiting. Computer modelling of the reaction scheme allows the generation of absorbance time plots of the same forms as those generated experimentally, i.e. first- or zero-order, both with or without induction periods. We suggest that the thiolate ion necessary to bring about Cu2+ reduction is either present as a thiol impurity or is generated in small quantities by partial hydrolysis of the nitrosothiol, which results in an induction period. Addition of small quantities of thiol removes the induction period and leads to catalysis but larger quantities bring about a rate reduction by, it is suggested, complexation of the Cu2+. For two very unreactive substrates, S-nitrosoglutathione and S-nitroso-N-acetylcysteine very large induction periods were observed, typically three hours. This results, we suggest, from competitive re-oxidation of Cu+ to Cu2+ by the dissolved oxygen. Experiments carried out anaerobically confirm this, since there is then no induction period. Addition of hydrogen peroxide extends the induction period ever further. The results are discussed in terms of the biological properties of S-nitrosothiols which are related to nitric oxide release.