Chemical reaction mechanisms in solution from brute force computational Arrhenius plots.
Chemical reaction mechanisms in solution from brute force computational Arrhenius plots.
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DOI：
10.1038/ncomms8293
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发表时间：
2015-06-01
影响因子：
16.6
通讯作者：
Aqvist, Johan
中科院分区：
文献类型：
--
作者：
Kazemi, Masoud;Aqvist, Johan
将化学反应的活化自由能分解为热力学和熵成分，可以提供溶液和酶中机制途径的宝贵特征。由于这种凝聚相反应涉及大量的自由度，可靠的熵估计所需的大量构型采样仍然超出了量子化学计算的范围。在这里，我们表明，对于水解脱氨基的胞苷和二氢胞苷在水中，如何直接计算机模拟的自由能分布的温度依赖性可以用来提取非常准确的热力学活化参数。模拟是基于经验价键模型，我们表明，所获得的能量是不敏感的，无论是通过量子力学计算或实验数据校准。热力学活化参数与实验结果非常一致，并允许替代机制之间的歧视，以及合理化的不同的激活熵和熵。 获得反应的活化熵和熵谱对于区分不同的反应机理是很重要的。在这里，作者使用计算方法来准确地获得水解脱氨基反应的活化自由能的熵/熵分量。
Decomposition of activation free energies of chemical reactions, into enthalpic and entropic components, can provide invaluable signatures of mechanistic pathways both in solution and in enzymes. Owing to the large number of degrees of freedom involved in such condensed-phase reactions, the extensive configurational sampling needed for reliable entropy estimates is still beyond the scope of quantum chemical calculations. Here we show, for the hydrolytic deamination of cytidine and dihydrocytidine in water, how direct computer simulations of the temperature dependence of free energy profiles can be used to extract very accurate thermodynamic activation parameters. The simulations are based on empirical valence bond models, and we demonstrate that the energetics obtained is insensitive to whether these are calibrated by quantum mechanical calculations or experimental data. The thermodynamic activation parameters are in remarkable agreement with experiment results and allow discrimination among alternative mechanisms, as well as rationalization of their different activation enthalpies and entropies. Obtaining activation entropies and enthalpies of a reaction is important for distinguishing between alternative reaction mechanisms. Here the authors use computational methods to accurately obtain the enthalpic/entropic components of the activation free energy for hydrolytic deamination reactions.
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影响因子：
5.6
作者：
Almatarneh, Mansour H.;Flinn, Christopher G.;Poirier, Raymond A.
通讯作者：
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影响因子：
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Uddin, Kabir M.;Flinn, Christopher G.;Warburton, Peter L.
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影响因子：
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Aqvist, Johan
影响因子：
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作者：
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通讯作者：
Sokalski, W. Andrzej
影响因子：
16.6
作者：
EIGEN, M
通讯作者：
EIGEN, M