The Mechanism of Cleavage and Isomerisation of RNA Promoted by an Efficient Dinuclear Zn2+ Complex
The Mechanism of Cleavage and Isomerisation of RNA Promoted by an Efficient Dinuclear Zn2+ Complex
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DOI：
10.1002/chem.201100721
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发表时间：
2012-01-01
影响因子：
4.3
通讯作者：
Williams, Nicholas H.
中科院分区：
文献类型：
--
作者：
Korhonen, Heidi;Mikkola, Satu;Williams, Nicholas H.
研究了在双核Zn ~（2+）配合物存在下尿苷3 ′-烷基磷酸酯的裂解和异构化反应。在中性条件下，1 mM 3的裂解速率加速约为106倍。最值得注意的是，复合物还促进磷酸二酯键的异构化，尽管速率增强更温和：在中性条件下，复合物3（1 mM）催化异构化约500倍。该反应的观察表明，这些底物的反应3催化进行通过一个逐步的机制，涉及一个中间体正膦。测定3-促进的裂解反应的β Ig值为-0.92，并且观察到范围为1.5至2.8的适度动力学溶剂氘同位素效应。异构化对反硝化基团的性质不太敏感，β值为-0.5，动力学溶剂氘同位素效应小于1.5。3-促进的裂解的这些特征中的大多数与核苷3 '-磷酸三酯的裂解非常相似。这些数据被解释的机制，其中的配合物主要作为亲电催化剂中和的电荷上的磷酸盐和稳定的中间体正膦，与一般的酸催化促进裂解反应。与三酯的行为相反，异构化明显慢于裂解;这表明在异构化过程中发生的几何形状的变化导致3和正膦中间体之间的稳定性低得多的复合物。
The cleavage and isomerisation of uridine 3'-alkylphosphates was studied in the presence of a dinuclear Zn2+complex, 3. The rate acceleration of the cleavage by 1 mM 3 is approximately 106-fold under neutral conditions. Most remarkably, the complex also promotes the isomerisation of phosphodiester bonds, although the rate-enhancement is more modest: under neutral conditions complex 3 (1 mM) catalyses isomerisation by about 500-fold. The observation of this reaction shows that the reactions of these substrates catalysed by 3 proceed through a stepwise mechanism involving an intermediate phosphorane. A beta lg value of -0.92 was determined for the 3-promoted cleavage reaction, and modest kinetic solvent deuterium isotope effects ranging from 1.5 to 2.8 were observed. Isomerisation was less sensitive to the nature of the esterifying group, with a beta value of -0.5, and the kinetic solvent deuterium isotope effects were less than 1.5. Most of these characteristics of the 3-promoted cleavage are very similar to those for the cleavage of nucleoside 3'-phosphotriesters. These data are explained by a mechanism in which the complex primarily acts as an electrophilic catalyst neutralising the charge on the phosphate and stabilising an intermediate phosphorane, with general acid catalysis promoting the cleavage reaction. In contrast to the behaviour of triesters, isomerisation is significantly slower than cleavage; this suggests that the changes in geometry that occur during isomerisation lead to a much less stable complex between 3 and the phosphorane intermediate.