Estimation of rate constants in nonlinear reactions involving chemical inactivation of oxidation catalysts
Estimation of rate constants in nonlinear reactions involving chemical inactivation of oxidation catalysts
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DOI：
10.1007/s10910-014-0322-4
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发表时间：
2014-05-01
影响因子：
1.7
通讯作者：
Collins, Terrence J.
中科院分区：
文献类型：
--
作者：
Emelianenko, Maria;Torrejon, Diego;Collins, Terrence J.
在过去的几十年里，大量的工作一直致力于开发过氧化物酶的小分子复制品，这些酶在代谢和解毒过程中激活过氧化氢。TAML激活剂是本研究的主题，是第一个全功能的小分子过氧化物酶模拟物。作为催化循环的一个重要特征，TAML活性中间体（活性催化剂，Ac）经历自杀性失活，损害功能性催化。在这里，自杀性失活和生产性催化之间的关系是严格解决数学和化学。我们专注于一个广义的催化循环，其中TAML失活步骤由其速率常数来描述，其中揭示的数据是在由使用非常低的催化剂浓度人为施加的底物（S）的不完全转化的制度中收集的。该系统具有非线性守恒律，并通过奇异摄动方法，这是用来获得系统参数之间的封闭形式的关系建模。导出一种新的方法，允许计算所有的催化循环中的速率常数，和，少至两个线性最小二乘拟合，为最小的数据集收集在任何条件下提供的S的氧化是不完全的。该方法便于确定描述催化剂使用寿命的临界速率常数，并大大减少了获得重要速率常数所需的实验工作.该方法被应用于一种新的TAML活化剂的行为，也描述了该活化剂的合成和表征.
Over the last decades, copious work has been devoted to the development of small molecule replicas of the peroxidase enzymes that activate hydrogen peroxide in metabolic and detoxifying processes. TAML activators that are the subject of this study are the first full functional, small molecule peroxidase mimics. As an important feature of the catalytic cycle, TAML reactive intermediates (active catalysts, Ac) undergo suicidal inactivation, compromising the functional catalysis. Herein the relationship between suicidal inactivation and productive catalysis is rigorously addressed mathematically and chemically. We focus on a generalized catalytic cycle in which the TAML inactivation step is delineated by its rate constant where the revealing data is collected in the regime of incomplete conversion of substrate (S) artificially imposed by the use of very low catalyst concentrations. The system exhibits a nonlinear conservation law and is modeled via a singular perturbation approach, which is used to obtain closed form relationships between system parameters. A new method is derived that allows to compute all the rate constants in the catalytic cycle, , and , with as little as two linear least squares fits, for the minimal data set collected under any conditions providing that the oxidation of S is incomplete. This method facilitates determination of , a critical rate constant that describes the operational lifetime of the catalyst, and greatly reduces the experimental work required to obtain the important rate constants.The approach was applied to the behavior of a new TAML activator, the synthesis and characterization of which are also described.