Mimicking enzymes: Cooperation between organic functional groups and metal ions in the cleavage of phosphate diesters
Mimicking enzymes: Cooperation between organic functional groups and metal ions in the cleavage of phosphate diesters
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DOI：
10.1002/chem.200600672
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发表时间：
2007-01-01
影响因子：
4.3
通讯作者：
Tonellato, Umberto
中科院分区：
文献类型：
--
作者：
Livieri, Monica;Mancin, Fabrizio;Tonellato, Umberto
制备了一系列衍生自双-2-吡啶甲胺结构的配体，它们带有额外的羟基或芳氨基，并研究了它们的锌-II配合物作为双-对-硝基苯磷酸（BNP）和2-羟丙基-对-硝基苯磷酸（HPNP）二酯裂解的催化剂。一个比较动力学研究表明，插入的有机基团，能够作为亲核试剂或作为氢键供体，大大增加了金属络合物的水解活性。对各个组的影响的分析表明，反应性的增加可以达到三个数量级。所研究的系统的效率提高，结合活性亲核试剂的低pK（a）值所产生的益处，导致BNP在pH 7下裂解的加速达六个数量级。pH依赖性反应性曲线遵循钟形曲线，并且在pH 9下观察到最大反应性。通过动力学分析、核磁共振实验和理论计算，对反应机理和配合物的结构进行了详细的研究。切割HPNP的复合物的反应性与观察到的BNP的反应性非常相似，但由于不同的反应机制，所实现的加速较低。
A series of ligands derived from the bis-2-pyridinylmethylamine structure, which bear either additional hydroxyl or aromatic amino groups, were prepared and their Zn-II complexes were studied as catalysts for the cleavage of bis-p-nitrophenyl phosphate (BNP) and 2-hydroxypropyl-p-nitrophenyl phosphate (HPNP) diesters. A comparative kinetic study indicated that the insertion of organic groups, capable of acting as nucleophiles or as hydrogen-bond donors, substantially increases the hydrolytic activity of the metal complex. Dissection of the effects of the individual groups revealed that the increase in reactivity can reach up to three orders of magnitude. The improved efficiency of the systems studied, combined with the benefits resulting from the low pK(a) value of the active nucleophile, result in an acceleration of the BNP cleavage at pH 7 of six orders of magnitude. The pH-dependent reactivity profiles follow a bell-shaped curve and the maximum reactivity is observed at pH 9. The mechanism of the reactions and the structure of the complexes were investigated in detail by means of kinetic analysis, NMR spectroscopy experiments, and theoretical calculations. The reactivity of the complexes that cleave HPNP closely resembles the reactivity observed for BNP, but the accelerations achieved are lower as a result of different reaction mechanisms.