Thermal stability of primary S-nitrosothiols:: Roles of autocatalysis and structural effects on the rate of nitric oxide release
Thermal stability of primary S-nitrosothiols:: Roles of autocatalysis and structural effects on the rate of nitric oxide release
复制标题
DOI：
10.1021/jp025756u
复制
发表时间：
2002-09-26
影响因子：
2.9
通讯作者：
Morgon, NH
中科院分区：
文献类型：
--
作者：
de Oliveira, MG;Shishido, SM;Morgon, NH
S-亚硝基硫醇（RSNOs）被认为在体内储存、运输和释放一氧化氮（NO）中起重要作用。虽然叔RSNO被认为是本质上比初级RSNO更稳定，初级RSNO的结构和热NO释放在溶液中的动力学之间的相关性尚未建立。我们的特点是热NO释放的动力学从三个主要RSNO：S-亚硝基半胱氨酸（CySNO），S-亚硝基-N-乙酰半胱氨酸（SNAG），和S-亚硝基谷胱甘肽（GSNO）在水溶液中。结果发现，NO的释放速率强烈地受溶液的初始浓度的影响。将CySNO和SNAC的浓度从1.0 x 10（-1）增加到61.0 mmol L-1，导致其初始分解速率分别增加5.7倍和14.6倍，而GSNO受到的影响要小得多（增加2倍）。然而，浓度的较小增加（0.1至1.0 mM）导致平均在三种情况下NO释放速率降低4.6倍。这一结果被分配到一个自催化效应的组合促进的二次反应的thyil自由基与正宗RSNO分子，这加速了在浓溶液中的分解反应，和一个nongeminate（扩散，笼外）自由基对重组效应，导致在稀溶液中的反应速率降低。在低浓度范围内，GSNO和SNAC显示出比CySNO显著更稳定。这一结果与MP2/6- 31 G（2df，p）//MP2/6- 31 G（d）理论水平下的单点能计算结果一致，表明SNAC中存在的乙酰氨基对增加S-N键强度起着关键作用。这些结果表明，溶液中不同S-亚硝基硫醇之间的稳定性比较必须仔细考虑浓度效应，并表明体内发现的主要RSNO的半衰期可以部分取决于其内在结构特性。
S-Nitrosothiols (RSNOs) are considered to play important roles in storing, transporting, and releasing nitric oxide (nitrogen monoxide, NO) in vivo. Although tertiary RSNOs are known to be intrinsically more stable than primary RSNOs, the correlation between the structure of primary RSNOs and the kinetics of thermal NO release in solution has not been established yet. We have characterized the kinetics of thermal NO release from three primary RSNOs: S-nitrosocysteine (CySNO), S-nitroso-N-acetylcysteine (SNAG), and S-nitrosoglutatione (GSNO) in aqueous solutions. It, was found that the rates of NO release are strongly affected by the initial concentration of the solutions. Increasing the concentration of CySNO and SNAC from 1.0 x 10(-1) to 61.0 mmol L-1 led to 5.7- and 14.6-fold increases in their initial rates of decomposition, respectively, whereas GSNO was much less affected (a 2-fold increase). However, a smaller increase in concentration (0.1 to 1.0 mM) led to a 4.6-fold decrease, on average, in the rates of NO release in the three cases. This result was assigned to the combination of an autocatalytic effect promoted by the secondary reaction of thyil radicals with authentic RSNO molecules, which accelerates the decomposition reaction in concentrated solutions, and a nongeminate (diffusive, outside the cage) radical pair recombination effect that leads to a reduction in the rates of reaction in dilute solutions. In the low-concentration range, GSNO and SNAC were shown to be significantly more stable than CySNO. This result is in accordance with the conclusions derived from single-point energy calculations at the MP2/6-31G(2df,p)//MP2/6-31G(d) level of theory, which have shown that the acetamido group that is present in SNAC plays a key role in increasing the S-N bond strength. These results show that comparisons of stability among different S-nitrosothiols in solution must take the concentration effect carefully into account and indicate that the half-lives of primary RSNOs found in vivo can be partially determined by their intrinsic structural properties.